Linee Guida 2023 SCA

European Heart Journal (2023) 44, 3720–3826 ESC GUIDELINES
https://doi.org/10.1093/eurheartj/ehad191
2023 ESC Guidelines for the management

of acute coronary syndromes
Developed by the task force on the management of acute coronary
syndromes of the European Society of Cardiology (ESC)
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Authors/Task Force Members: Robert A. Byrne *†, (Chairperson) (Ireland),
Xavier Rossello ‡, (Task Force Co-ordinator) (Spain), J.J. Coughlan ‡,
(Task Force Co-ordinator) (Ireland), Emanuele Barbato (Italy), Colin Berry
(United Kingdom), Alaide Chieffo (Italy), Marc J. Claeys (Belgium),
Gheorghe-Andrei Dan (Romania), Marc R. Dweck (United Kingdom),
Mary Galbraith (United Kingdom), Martine Gilard (France),
Lynne Hinterbuchner (Austria), Ewa A. Jankowska (Poland), Peter Jüni
(United Kingdom), Takeshi Kimura (Japan), Vijay Kunadian (United Kingdom),
Margret Leosdottir (Sweden), Roberto Lorusso (Netherlands),
Roberto F.E. Pedretti (Italy), Angelos G. Rigopoulos (Greece),
Maria Rubini Gimenez (Germany), Holger Thiele (Germany),
Pascal Vranckx (Belgium), Sven Wassmann (Germany), Nanette Kass Wenger
(United States of America), Borja Ibanez *†, (Chairperson) (Spain), and ESC
Scientific Document Group
* Corresponding authors: Robert A. Byrne, Department of Cardiology and Cardiovascular Research Institute (CVRI) Dublin, Mater Private Network, Dublin, Ireland, and School of Pharmacy
and Biomolecular Sciences, RCSI University of Medicine and Health Sciences, Dublin, Ireland. Tel: +353-1-2483190, E-mail: robertabyrne@rcsi.ie; and Borja Ibanez, Clinical Research
Department, Centro Nacional de Investigaciones Cardiovasculares Carlos III (CNIC), Madrid, Spain, and Cardiology Department, IIS-Fundación Jiménez Díaz University Hospital, Madrid,
Spain, CIBERCV, ISCIII, Madrid, Spain. Tel: +3491 4531200, E-mail: bibanez@cnic.es
†
The two Chairpersons contributed equally to the document and are joint corresponding authors.
‡
The two Task Force Co-ordinators contributed equally to the document.
Author/Task Force Member affiliations are listed in author information.
ESC Clinical Practice Guidelines (CPG) Committee: listed in the Appendix.
ESC subspecialty communities having participated in the development of this document:
Associations: Association of Cardiovascular Nursing & Allied Professions (ACNAP), Association for Acute CardioVascular Care (ACVC), European Association of Cardiovascular Imaging
(EACVI), European Association of Preventive Cardiology (EAPC), European Association of Percutaneous Cardiovascular Interventions (EAPCI), European Heart Rhythm Association (EHRA),
and Heart Failure Association (HFA).
Working Groups: Cardiovascular Pharmacotherapy, Cardiovascular Surgery, E-Cardiology, Myocardial and Pericardial Diseases, Thrombosis.
Patient Forum
The content of these European Society of Cardiology (ESC) Guidelines has been published for personal and educational use only. No commercial use is authorized. No part of the ESC
Guidelines may be translated or reproduced in any form without written permission from the ESC. Permission can be obtained upon submission of a written request to Oxford
University Press, the publisher of the European Heart Journal, and the party authorized to handle such permissions on behalf of the ESC (journals.permissions@oup.com).
Disclaimer. The ESC Guidelines represent the views of the ESC and were produced after careful consideration of the scientific and medical knowledge and the evidence available at the time
of their publication. The ESC is not responsible in the event of any contradiction, discrepancy, and/or ambiguity between the ESC Guidelines and any other official recommendations or
guidelines issued by the relevant public health authorities, in particular in relation to good use of healthcare or therapeutic strategies. Health professionals are encouraged to take the
ESC Guidelines fully into account when exercising their clinical judgment, as well as in the determination and the implementation of preventive, diagnostic or therapeutic medical strategies;
however, the ESC Guidelines do not override, in any way whatsoever, the individual responsibility of health professionals to make appropriate and accurate decisions in consideration of each
patient’s health condition and in consultation with that patient and, where appropriate and/or necessary, the patient’s caregiver. Nor do the ESC Guidelines exempt health professionals from
taking into full and careful consideration the relevant official updated recommendations or guidelines issued by the competent public health authorities, in order to manage each patient’s case
in light of the scientifically accepted data pursuant to their respective ethical and professional obligations. It is also the health professional’s responsibility to verify the applicable rules and
regulations relating to drugs and medical devices at the time of prescription.
This article is co-published with permission in European Heart Journal and European Heart Journal - Acute Cardiovascular Care. All rights reserved. © The European Society of Cardiology
2023. The articles are identical except for stylistic differences in keeping with each journal’s style. Either citation can be used when citing this article. For permissions, please e-mail:
journals.permissions@oup.com
ESC Guidelines 3721
Document Reviewers: Sigrun Halvorsen, (Clinical Practice Guidelines Review Co-ordinator) (Norway),
Stefan James, (Clinical Practice Guidelines Review Co-ordinator) (Sweden), Magdy Abdelhamid (Egypt),
Victor Aboyans (France), Nina Ajmone Marsan (Netherlands), Sotiris Antoniou (United Kingdom),
Riccardo Asteggiano (Italy), Maria Bäck (Sweden), Davide Capodanno (Italy), Ruben Casado-Arroyo (Belgium),
Salvatore Cassese (Germany), Jelena Čelutkienė (Lithuania), Maja Cikes (Croatia), Jean-Philippe Collet (France),
Gregory Ducrocq (France), Volkmar Falk (Germany), Laurent Fauchier (France), Tobias Geisler (Germany), Diana
A. Gorog (United Kingdom), Lene Holmvang (Denmark), Tiny Jaarsma (Sweden), Hywel Wynne Jones (United
Kingdom), Lars Køber (Denmark), Konstantinos C. Koskinas (Switzerland), Dipak Kotecha (United Kingdom),
Konstantin A. Krychtiuk (Austria), Ulf Landmesser (Germany), George Lazaros (Greece), Basil S. Lewis (Israel),
Bertil Lindahl (Sweden), Ales Linhart (Czech Republic), Maja-Lisa Løchen (Norway), Mamas A. Mamas (United
Kingdom), John William McEvoy (Ireland), Borislava Mihaylova (United Kingdom), Richard Mindham (United
Kingdom), Christian Mueller (Switzerland), Lis Neubeck (United Kingdom), Josef Niebauer (Austria), Jens

Cosedis Nielsen (Denmark), Alexander Niessner (Austria), Valeria Paradies (Netherlands), Agnes A. Pasquet
(Belgium), Steffen E. Petersen (United Kingdom), Eva Prescott (Denmark), Amina Rakisheva (Kazakhstan),
Bianca Rocca (Italy), Giuseppe M.C. Rosano (Italy), Leyla Elif Sade (United States of America / Türkiye),
François Schiele (France), Jolanta M. Siller-Matula (Austria), Christian Sticherling (Switzerland), Robert F. Storey
(United Kingdom), Matthias Thielmann (Germany), Christiaan Vrints (Belgium), Stephan Windecker
(Switzerland), Rune Wiseth (Norway), and Adam Witkowski (Poland)
All experts involved in the development of these guidelines have submitted declarations of interest. These have
been compiled in a report and simultaneously published in a supplementary document to the guidelines. The
report is also available on the ESC website www.escardio.org/Guidelines
See the European Heart Journal online for supplementary documents that include background information and
evidence tables.
Keywords Guidelines • Acute cardiac care • Acute coronary syndrome • Antithrombotic therapy • Fibrinolysis • High-
sensitivity troponin • Invasive strategy • MINOCA • Myocardial infarction • Non-ST-elevation myocardial infarction
• Patient-centred care • Percutaneous coronary intervention • Recommendations • Reperfusion therapy •
Revascularization • Secondary prevention • ST-segment elevation myocardial infarction • Unstable angina
Table of contents 3.3.2. Central laboratory vs. point of care .......................................

3.3.3. Confounders of cardiac troponin concentration .............
3739
3739
1. Preamble .............................................................................................................. 3727 3.3.4. Rapid ‘rule-in’ and ‘rule-out’ algorithms ................................ 3739
2. Introduction ....................................................................................................... 3728 3.3.4.1. European Society of Cardiology 0 h/1 h and 0 h/2 h
2.1. Definitions | Acute coronary syndromes and myocardial algorithms .................................................................................................. 3740
infarction ............................................................................................................. 3730 3.3.4.1.1. Rule-out ............................................................................. 3740
2.2. Epidemiology of acute coronary syndromes .............................. 3732 3.3.4.1.2. Rule-in ................................................................................ 3740
2.3. Number and breakdown of classes of recommendations ... 3732 3.3.4.1.3. Observe ............................................................................. 3740
2.4. What is new ............................................................................................. 3733 3.3.4.2. Practical guidance on how to implement the
3. Triage and diagnosis ........................................................................................ 3735 European Society of Cardiology 0 h/1 h algorithm ................. 3742
3.1. Clinical presentation and physical examination ......................... 3735 3.3.5. Other biomarkers .......................................................................... 3742
3.1.1. Clinical presentation ...................................................................... 3735 3.4. Diagnostic tools | Non-invasive imaging ....................................... 3742
3.1.2. History taking and physical examination .............................. 3737 3.4.1. Echocardiography ........................................................................... 3742
3.2. Diagnostic tools | Electrocardiogram ............................................ 3737 3.4.2. Computed tomography ............................................................... 3742
3.2.1. Acute coronary syndrome with persistent ST-segment 3.4.3. Cardiac magnetic resonance imaging with or without
elevation (suspected ST-elevation myocardial infarction) ......... 3738 stress testing ................................................................................................. 3742
3.2.2. Acute coronary syndrome without persistent ST- 3.5. Differential diagnosis for acute chest pain .................................. 3743
segment elevation (non-ST elevation acute coronary 4. Initial measures for patients presenting with suspected acute
syndrome) ...................................................................................................... 3738 coronary syndrome | Initial treatment ........................................................ 3743
3.3. Diagnostic tools | Biomarkers ........................................................... 3739 4.1. Pre-hospital logistics of care .............................................................. 3743
3.3.1. High-sensitivity cardiac troponins ............................................ 3739 4.1.1. Time to treatment ......................................................................... 3743
3722 ESC Guidelines
4.1.2. Healthcare systems and system delays .................................. 3743 6.3.1. Shortening dual antiplatelet therapy ....................................... 3756
4.1.3. Emergency medical services ....................................................... 3743 6.3.2. De-escalation from potent P2Y12 inhibitor to
4.1.4. General practitioners .................................................................... 3744 clopidogrel ..................................................................................................... 3756
4.1.5. Organization of ST-elevation myocardial infarction 6.3.3. Summary of alternative antiplatelet strategies to reduce
treatment in networks .............................................................................. 3744 bleeding risk in the first 12 months after acute coronary
4.2. Emergency care ....................................................................................... 3744 syndrome ........................................................................................................ 3757
4.2.1. Initial diagnosis and monitoring ................................................ 3744 6.4. Long-term treatment ............................................................................ 3759
4.2.2. Acute pharmacotherapy .............................................................. 3744 6.4.1. Prolonging antithrombotic therapy beyond 12 months 3759
4.2.2.1. Oxygen ....................................................................................... 3744 6.5. Antiplatelet therapy in patients requiring oral
4.2.2.2. Nitrates ...................................................................................... 3744 anticoagulation ................................................................................................. 3760
4.2.2.3. Pain relief ................................................................................... 3744 6.5.1. Acute coronary syndrome patients requiring
4.2.2.4. Intravenous beta-blockers .................................................. 3744 anticoagulation ............................................................................................. 3760

5. Acute-phase management of patients with acute coronary 6.5.2. Patients requiring vitamin K antagonists or undergoing
syndrome .................................................................................................................. 3745 coronary artery bypass surgery ............................................................ 3762
5.1. Selection of invasive strategy and reperfusion therapy ......... 3745 6.6. Antithrombotic therapy as an adjunct to fibrinolysis ............. 3762
5.2. Acute coronary syndrome managed with invasive strategy 3745 6.7. Antithrombotic therapy in patients not undergoing
5.2.1. Primary percutaneous coronary intervention strategy for reperfusion ......................................................................................................... 3762
ST-elevation myocardial infarction ...................................................... 3745 7. Acute coronary syndrome with unstable presentation .................. 3762
5.2.1.1. Invasive strategy in ST-elevation myocardial infarction 7.1. Out-of-hospital cardiac arrest in acute coronary syndrome 3763
late presenters ......................................................................................... 3747 7.1.1. Systems of care ................................................................................ 3763
5.2.2. Immediate invasive strategy for non-ST elevation acute 7.2. Cardiogenic shock complicating acute coronary syndrome 3763
coronary syndrome .................................................................................... 3747 8. Management of acute coronary syndrome during hospitalization 3764
5.2.3. Routine vs. selective invasive strategy .................................... 3747 8.1. Coronary care unit/intensive cardiac care unit ......................... 3764
5.2.3.1. Early vs. delayed invasive strategy for non-ST 8.1.1. Monitoring ......................................................................................... 3764
elevation acute coronary syndrome .............................................. 3747 8.1.2. Ambulation ........................................................................................ 3764
5.2.4. Summary of invasive strategies for patients with non-ST 8.1.3. Length of stay in the intensive cardiac care unit ............... 3765
elevation acute coronary syndrome ................................................... 3747 8.2. In-hospital care ........................................................................................ 3765
5.3. Fibrinolysis and pharmaco-invasive strategy in patients with 8.2.1. Length of hospital stay ................................................................. 3765
ST-elevation myocardial infarction .......................................................... 3749 8.2.2. Risk assessment ............................................................................... 3765
5.3.1. Benefit and indication of fibrinolysis ....................................... 3749 8.2.2.1. Clinical risk assessment ........................................................ 3765
5.3.1.1. Pre-hospital fibrinolysis ........................................................ 3749 8.2.2.2. Imaging risk assessment ....................................................... 3765
5.3.1.2. Angiography and percutaneous coronary 8.2.2.3. Biomarkers for risk assessment ....................................... 3765
intervention after fibrinolysis (pharmaco-invasive strategy) 3749 8.2.2.4. Bleeding risk assessment ..................................................... 3765
5.3.1.2.1. Comparison of fibrinolytic agents .......................... 3749 8.2.2.5. Integrating ischaemic and bleeding risks ....................... 3765
5.3.1.2.2. Hazards of fibrinolysis and contraindications .... 3749 9. Technical aspects of invasive strategies .................................................. 3766
5.4. Patients not undergoing reperfusion ............................................. 3749 9.1. Percutaneous coronary intervention ............................................. 3766
5.4.1. Patients who are not candidates for invasive coronary 9.1.1. Vascular access ................................................................................ 3766
angiography .................................................................................................... 3749 9.1.2. Intravascular imaging/physiology of the infarct-related
5.4.2. Patients with coronary artery disease not amenable to artery ................................................................................................................ 3766
revascularization .......................................................................................... 3749 9.1.2.1. Intravascular imaging ............................................................. 3766
6. Antithrombotic therapy ................................................................................ 3750 9.1.2.2. Intravascular physiology ....................................................... 3767
6.1. Antiplatelet therapy in the acute phase ....................................... 3752 9.1.3. Timing of revascularization with percutaneous coronary
6.1.1. Oral antiplatelet therapy ............................................................. 3752 intervention ................................................................................................... 3767
6.1.2. Timing of loading dose of oral antiplatelet therapy ......... 3753 9.1.4. Balloons and stents ........................................................................ 3768
6.1.2.1. Pre-treatment in patients with suspected ST- 9.1.5. Embolic protection and microvascular salvage strategies 3768
elevation myocardial infarction ........................................................ 3753 9.1.5.1. Thrombus aspiration ............................................................ 3768
6.1.2.2. Pre-treatment in patients with non-ST-elevation 9.1.5.2. Interventions to protect the microcirculation .......... 3768
acute coronary syndrome .................................................................. 3753 9.2. Coronary artery bypass grafting ...................................................... 3768
6.1.2.3. Summary of pre-treatment strategies ........................... 3753 9.2.1. Indication and timing of coronary artery bypass grafting in
6.1.3. Intravenous antiplatelet drugs ................................................... 3753 acute coronary syndrome patients ..................................................... 3768
6.2. Anticoagulant treatment in the acute phase .............................. 3754 9.2.2. Technical considerations specific to acute coronary
6.2.1. Anticoagulation in patients with ST-elevation myocardial syndrome patients ...................................................................................... 3768
infarction undergoing primary percutaneous coronary 9.3. Spontaneous coronary artery dissection ..................................... 3768
intervention ................................................................................................... 3754 9.3.1. Intravascular imaging ..................................................................... 3769
6.2.2. Anticoagulation in patients with non-ST-elevation acute 9.3.2. Revascularization ............................................................................. 3769
coronary syndrome undergoing angiography and percutaneous 10. Management of patients with multivessel disease ........................... 3769
coronary intervention if indicated ....................................................... 3754 10.1. Management of multivessel disease in acute coronary
6.3. Maintenance antithrombotic therapy after revascularization 3755 syndrome complicated by cardiogenic shock ..................................... 3769
ESC Guidelines 3723
10.2. Patients with multivessel coronary artery disease 13.3.8. Vaccination ...................................................................................... 3787
undergoing primary percutaneous coronary intervention ............ 3770 13.3.9. Anti-inflammatory drugs ........................................................... 3787
10.3. Timing of non-infarct-related artery revascularization in 13.3.10. Hormone replacement therapy .......................................... 3787
acute coronary syndrome ........................................................................... 3771 14. Patient perspectives ..................................................................................... 3788
10.3.1. Patients presenting with ST-elevation myocardial 14.1. Patient-centred care ........................................................................... 3788
infarction and multivessel coronary artery disease ...................... 3771 14.2. Shared decision-making ..................................................................... 3789
10.3.2. Patients presenting with non-ST-elevation acute 14.3. Informed consent ................................................................................ 3789
coronary syndrome and multivessel coronary artery disease . 3771 14.4. Research participation and consent in the acute setting .... 3790
10.4. Evaluation of non-infarct-related artery stenosis severity 14.5. Patient satisfaction and expectations .......................................... 3790
(angiography vs. physiology) ....................................................................... 3771 14.6. Patient-reported outcome measures and patient-reported
10.5. Hybrid revascularization ................................................................... 3772 experience measures ..................................................................................... 3791
11. Myocardial infarction with non-obstructive coronary arteries . 3772 14.7. Preparation for discharge ................................................................. 3791

12. Special situations ............................................................................................ 3775 15. Key messages .................................................................................................. 3791
12.1. Type 2 myocardial infarction and acute myocardial injury 3775 16. Gaps in evidence ............................................................................................ 3793
12.2. Complications ....................................................................................... 3775 17. Sex differences ............................................................................................... 3795
12.2.1. Heart failure ................................................................................... 3775 18. ‘What to do’ and ‘What not to do’ messages from the
12.2.2. Mechanical complications ......................................................... 3776 Guidelines ................................................................................................................. 3796
12.2.3. Left ventricular thrombus ......................................................... 3776 19. Quality indicators .......................................................................................... 3801
12.2.4. Post-acute coronary syndrome pericarditis ..................... 3776 20. Supplementary data ...................................................................................... 3801
12.2.5. Arrhythmias .................................................................................... 3776 21. Data availability statement ......................................................................... 3801
12.2.5.1. Atrial fibrillation .................................................................... 3776 22. Author information ...................................................................................... 3801
12.2.5.2. Ventricular arrhythmias .................................................... 3777 23. Appendix ........................................................................................................... 3801
12.2.6. Bleeding ............................................................................................ 3777 24. References ........................................................................................................ 3802
12.2.6.1. Management of bleeding .................................................. 3777
12.3. Comorbid conditions ......................................................................... 3778
12.3.1. Patients at high bleeding risk and with blood disorders
(anaemia and thrombocytopaenia) ..................................................... 3778
Tables of Recommendations
12.3.2. Chronic kidney disease .............................................................. 3779 Recommendation Table 1 — Recommendations for clinical and
12.3.3. Diabetes mellitus .......................................................................... 3779 diagnostic tools for patients with suspected acute coronary
12.3.4. Older adults with frailty and multimorbidity ................... 3779 syndrome .................................................................................................................. 3738
12.3.4.1. The older person ................................................................. 3779 Recommendation Table 2 — Recommendations for non-invasive
12.3.4.2. Frailty and multimorbidity ................................................ 3779 imaging in the initial assessment of patients with suspected acute
12.3.5. Pregnancy ........................................................................................ 3780 coronary syndrome .............................................................................................. 3742
12.3.6. Drug abuse ...................................................................................... 3780 Recommendation Table 3 — Recommendations for the initial
management of patients with acute coronary syndrome ................... 3745
12.3.7. Patients with cancer .................................................................... 3780
Recommendation Table 4 — Recommendations for reperfusion
12.3.8. Coronavirus disease (COVID-19) ........................................ 3780
therapy and timing of invasive strategy ....................................................... 3750
13. Long-term treatment ................................................................................... 3781
Recommendation Table 5 — Recommendations for antiplatelet and
13.1. Cardiac rehabilitation ......................................................................... 3783
anticoagulant therapy in acute coronary syndrome .............................. 3758
13.1.1. Comprehensive cardiac rehabilitation ................................. 3783
Recommendation Table 6 — Recommendations for
13.1.2. Digital health .................................................................................. 3783
alternative antithrombotic therapy regimens ........................................... 3759
13.1.3. Adherence and persistence ..................................................... 3783 Recommendation Table 7 — Recommendations for fibrinolytic
13.2. Lifestyle management ......................................................................... 3783 therapy ....................................................................................................................... 3762
13.2.1. Tobacco ........................................................................................... 3783 Recommendation Table 8 — Recommendations for cardiac arrest
13.2.2. Nutrition and alcohol ................................................................. 3783 and out-of-hospital cardiac arrest ................................................................. 3763
13.2.3. Physical activity and exercise .................................................. 3784 Recommendation Table 9 — Recommendations for cardiogenic
13.2.4. Psychological considerations ................................................... 3784 shock .......................................................................................................................... 3764
13.2.5. Resumption of activities ............................................................ 3784 Recommendation Table 10 — Recommendations for in-hospital
13.3. Pharmacological treatment .............................................................. 3784 management ............................................................................................................ 3766
13.3.1. Antithrombotic therapy ............................................................ 3784 Recommendation Table 11 — Recommendations for technical
13.3.2. Lipid-lowering therapy ............................................................... 3784 aspects of invasive strategies ............................................................................ 3769
13.3.3. Beta-blockers ................................................................................. 3785 Recommendation Table 12 — Recommendations for management
13.3.4. Nitrates and calcium channel blockers ............................... 3786 of patients with multivessel disease .............................................................. 3772
13.3.5. Renin–angiotensin–aldosterone system inhibitors ......... 3786 Recommendation Table 13 — Recommendations for myocardial
13.3.6. Medications for diabetes ........................................................... 3786 infarction with non-obstructive coronary arteries ................................. 3775
13.3.6.1. Sodium–glucose co-transporter 2 inhibitors ........... 3786 Recommendation Table 14 — Recommendations for acute
13.3.6.2. Glucagon-like peptide-1 receptor agonists .............. 3787 coronary syndrome complications ................................................................ 3777
13.3.7. Proton pump inhibitors ............................................................. 3787 Recommendation Table 15 — Recommendations for acute
coronary syndrome comorbid conditions ................................................. 3781
3724 ESC Guidelines
Recommendation Table 16 — Recommendations for long-term Figure 17 Long-term management after acute coronary syndrome 3782
management ............................................................................................................ 3787 Figure 18 Lipid-lowering therapy in ACS patients .................................. 3785
Recommendation Table 17 — Recommendations for patient Figure 19 A person-centred approach to the ACS journey .............. 3789
perspectives in acute coronary syndrome care ....................................... 3791 Figure 20 Acute coronary syndrome patient expectations ................ 3790
List of tables
Table 1 Classes of recommendations .......................................................... 3728
Abbreviations and acronyms
Table 2 Levels of evidence ................................................................................ 3728 AβYSS Beta Blocker Interruption After
Table 3 Definitions of terms related to invasive strategy and Uncomplicated Myocardial Infarction
reperfusion therapy commonly used in this document ....................... 3731 ACCOAST A Comparison of Prasugrel at the Time of
Table 4 New recommendations .................................................................... 3733 Percutaneous Coronary Intervention or as
Table 5 Revised recommendations ............................................................... 3734 Pretreatment at the Time of Diagnosis in

Table 6 Dose regimen of antiplatelet and anticoagulant drugs in Patients with Non-ST Elevation Myocardial
acute coronary syndrome patients ............................................................... 3751 Infarction
Table 7 Suggested strategies to reduce bleeding risk related to ACE Angiotensin-converting enzyme
percutaneous coronary intervention ............................................................ 3760 ACS Acute coronary syndrome
Table 8 Gaps in evidence .................................................................................. 3793 AF Atrial fibrillation
Table 9 ‘What to do’ and ‘What not to do’ ............................................. 3796 AFIRE Atrial Fibrillation and Ischemic Events With
Rivaroxaban in Patients With Stable Coronary
List of figures AMI
Artery Disease
Acute myocardial infarction
Figure 1 Central illustration .............................................................................. 3729 ARB Angiotensin receptor blocker
Figure 2 The spectrum of clinical presentations, electrocardiographic ARC-HBR Academic Research Consortium for High
findings, and high-sensitivity cardiac troponin levels in patients with Bleeding Risk
acute coronary syndrome ................................................................................. 3730 ARNI Angiotensin receptor/neprilysin inhibitor
Figure 3 Classification of patients presenting with suspected acute ASCVD Atherosclerotic cardiovascular disease
coronary syndrome: from a working to a final diagnosis .................... 3732 ASSENT 3 ASsessment of the Safety and Efficacy of a New
Figure 4 An overview of the initial triage, management and Thrombolytic 3
investigation of patients who present with signs and symptoms ATLANTIC Administration of Ticagrelor in the Cath Lab or
potentially consistent with acute coronary syndrome ......................... 3736 in the Ambulance for New ST Elevation
Figure 5 The A.C.S. assessment for the initial evaluation of patients Myocardial Infarction to Open the Coronary
with suspected acute coronary syndrome ................................................. 3737 Artery
Figure 6 The 0 h/1 h or 0 h/2 h rule-out and rule-in algorithms using AUGUSTUS An Open-Label, 2 × 2 Factorial, Randomized
high-sensitivity cardiac troponin assays in patients presenting to the Controlled, Clinical Trial to Evaluate the Safety
emergency department with suspected NSTEMI and without an of Apixaban Versus Vitamin K Antagonist and
indication for immediate invasive angiography ......................................... 3741 Aspirin Versus Aspirin Placebo in Patients With
Figure 7 Modes of presentation and pathways to invasive Atrial Fibrillation and Acute Coronary
management and myocardial revascularization in patients presenting Syndrome or Percutaneous Coronary
with STEMI .............................................................................................................. 3746 Intervention
Figure 8 Selection of invasive strategy and reperfusion therapy in AV Atrioventricular
patients presenting with NSTE-ACS ............................................................ 3748 BARC Bleeding Academic Research Consortium
Figure 9 Antithrombotic treatments in acute coronary syndrome: b.i.d. Bis in die (twice a day)
pharmacological targets ...................................................................................... 3752 BBB Bundle branch block
Figure 10 Recommended default antithrombotic therapy regimens BEACON Better Evaluation of Acute Chest Pain with
in acute coronary syndrome patients without an indication for oral Coronary Computed Tomography Angiography
anticoagulation ....................................................................................................... 3755 BETAMI BEtablocker Treatment After Acute
Figure 11 Alternative antiplatelet strategies to reduce bleeding risk in Myocardial Infarction in Patients Without
the first 12 months after an ACS .................................................................. 3757 Reduced Left Ventricular Systolic Function
Figure 12 Antithrombotic regimens in patients with acute coronary BMS Bare metal stent
syndrome and an indication for oral anticoagulation ................................ 3761 BNP Brain natriuretic peptide
Figure 13 A practical algorithm to guide intravascular imaging in CABG Coronary artery bypass grafting
acute coronary syndrome patients ............................................................... 3767 CAD Coronary artery disease
Figure 14 Algorithm for the management of acute coronary CAPITAL-RCT Carvedilol Post-Intervention Long-Term
syndrome patients with multivessel coronary artery disease ............ 3770 Administration in Large-scale Randomized
Figure 15 Underlying causes for patients with a working diagnosis of Controlled Trial
myocardial infarction with non-obstructive coronary arteries ......... 3773 CAPRICORN CArvedilol Post-infaRct survIval COntRolled
Figure 16 Evaluation of patients with a working diagnosis of evaluatioN
MINOCA .................................................................................................................. 3774 CCS Chronic coronary syndrome
ESC Guidelines 3725
CCTA Coronary computed tomography angiography ESC European Society of Cardiology

CCU Coronary care unit EXAMINATION Everolimus-Eluting Stents Versus Bare-Metal
CHA2DS2-VASc Congestive heart failure, Hypertension, Age, Stents in ST Segment Elevation Myocardial
Diabetes, Stroke or TIA-Vascular disease Infarction
CHAMPION PCI Cangrelor versus Standard Therapy to ExTRACT-TIMI 25 Enoxaparin and Thrombolysis Reperfusion for
Achieve Optimal Management of Platelet Acute myocardial infarction Treatment
Inhibition Thrombolysis In Myocardial Infarction—Study 25
CHAMPION A Clinical Trial Comparing Cangrelor to FAME Fractional Flow Reserve versus Angiography
PHOENIX Clopidogrel Standard Therapy in Subjects for Multivessel Evaluation
Who Require Percutaneous Coronary FAMOUS-NSTEMI Fractional flow reserve (FFR) versus
Intervention angiography in guiding management to
CHAMPION Cangrelor Versus Standard Therapy to optimise outcomes in non-ST segment

PLATFORM Achieve Optimal Management of Platelet elevation myocardial infarction
Inhibition FAST-MI French Registry of Acute ST-elevation and
CKD Chronic kidney disease non-ST-elevation Myocardial Infarction
CMR Cardiac magnetic resonance FFR Fractional flow reserve
CI Confidence interval FLOWER-MI Flow Evaluation to Guide Revascularization in
COACT Coronary Angiography after Cardiac Arrest Multivessel ST-Elevation Myocardial Infarction
COLCOT Colchicine Cardiovascular Outcomes Trial FMC First medical contact
COMFORTABLE- Comparison of Biolimus Eluted From an Erodible GLP-1RA Glucagon-like peptide-1 receptor agonist
AMI Stent Coating With Bare Metal Stents in Acute GP Glycoprotein
ST-Elevation Myocardial Infarction GRACE Global Registry of Acute Coronary Events
COMPARE-ACUTE Comparison Between FFR Guided HBR High bleeding risk
Revascularization Versus Conventional HCR Hybrid coronary revascularization
Strategy in Acute STEMI Patients With MVD HF Heart failure
COMPASS Cardiovascular Outcomes for People Using HFrEF Heart failure with reduced ejection fraction
Anticoagulation Strategies HOST-REDUCE-P- Harmonizing Optimal Strategy for Treatment
COMPLETE Complete vs. Culprit-only Revascularization to OLYTECH-ACS of Coronary Artery Diseases Trial—
Treat Multivessel Disease After Early PCI for Comparison of REDUCTION of PrasugrEl
STEMI Dose & POLYmer TECHnology in ACS
COVID-19 Coronavirus disease 2019 Patients
CR Cardiac rehabilitation HR Hazard ratio
CRT Cardiac resynchronization therapy— HR-QoL Health-related quality of life
defibrillator/pacemaker hs-cTn High-sensitivity cardiac troponin
CS Cardiogenic shock IABP Intra-aortic balloon counter pulsation/pumping
CT Computed tomography IABP-SHOCK II Intraaortic Balloon Pump in Cardiogenic Shock II
CV Cardiovascular ICA Invasive coronary angiography
CVD Cardiovascular disease ICCU Intensive cardiac care unit
CvLPRIT Complete versus Lesion-only Primary PCI Trial ICD Implantable cardioverter defibrillator
cTn Cardiac troponin ICU Intensive care unit
CULPRIT-SHOCK Culprit Lesion Only PCI versus Multivessel PCI IMPROVE-IT Improved Reduction of Outcomes: Vytorin
in Cardiogenic Shock Efficacy International Trial
DANAMI-3– Third Danish Study of Optimal Acute INR International normalized ratio
PRIMULTI Treatment of Patients with ST-Segment IRA Infarct-related artery
Elevation Myocardial Infarction—Primary PCI ISAR-REACT 5 Intracoronary stenting and Antithrombotic
in Multivessel Disease regimen Rapid Early Action for Coronary
DANBLOCK Danish Trial of Beta Blocker Treatment After Treatment
Myocardial Infarction Without Reduced ISIS-4 Fourth International Study of Infarct Survival
Ejection Fraction i.v. Intravenous
DAPT Dual antiplatelet therapy IVUS Intravascular ultrasound
DAT Dual antithrombotic therapy LAD Left anterior descending
DCB Drug-coated balloon LBBB Left bundle branch block
DES Drug-eluting stent(s) LD Loading dose
DM Diabetes mellitus LDL-C Low-density lipoprotein-cholesterol
ECG Electrocardiography/gram LIMA Left internal mammary artery
ECMO Extracorporeal membrane oxygenation LMWH Low-molecular-weight heparin
eGFR Estimated glomerular filtration rate LoDoCo2 Low-dose Colchicine trial-2
ED Emergency department LV Left ventricular(cle)
EMS Emergency medical service(s) LVAD Left ventricular assist device
EPHESUS Eplerenone Post-AMI Heart failure Efficacy and LVEF Left ventricular ejection fraction
SUrvival Study MACE Major adverse cardiovascular events
3726 ESC Guidelines
MASTER DAPT Management of High Bleeding Risk Patients PPI Proton pump inhibitor
Post Bioresorbable Polymer Coated Stent PPV Positive predictive value
Implantation With an Abbreviated Versus PRAMI Preventive Angioplasty in Myocardial Infarction
Prolonged DAPT Regimen PREM Patient-reported experience measure
MATRIX Minimizing Adverse Haemorrhagic Events by PROM Patient-reported outcome measure
Transradial Access Site and Systemic QI Quality indicator
Implementation of angioX RAAS Renin–angiotensin–aldosterone system
MCS Mechanical circulatory support RAPID-CTCA Rapid Assessment of Potential Ischaemic heart
MD Maintenance dose Disease with CTCA
MI Myocardial infarction RCT Randomized controlled trial
MINOCA Myocardial infarction with non-obstructive REALITY Restrictive and Liberal Transfusion
coronary arteries Strategies in Patients With Acute Myocardial

MRA Mineralocorticoid receptor antagonist Infarction
MVD Multivessel disease REBOOT-CNIC TREatment With Beta-blockers After
MVO Microvascular obstruction myOcardial Infarction withOut Reduced
NOAC Non-vitamin K antagonist oral anticoagulant Ejection fracTion
NORSTENT Norwegian Coronary Stent Trial REDUCE-SWEDE- Evaluation of Decreased Usage of Betablockers
NPV Negative predictive value HEART After Myocardial Infarction in the
NRT Nicotine replacement therapy SWEDEHEART Registry
NSTE Non-ST elevation REMINDER Double-Blind, Randomized,
NSTE-ACS Non-ST elevation acute coronary syndrome Placebo-Controlled Trial Evaluating The Safety
NSTEMI Non-ST-elevation myocardial infarction And Efficacy Of Early Treatment With
NT-pro BNP N-terminal pro B-type natriuretic peptide Eplerenone In Patients With Acute Myocardial
NYHA New York Heart Association Infarction
o.d. Once a day REVELATION REVascularization With PaclitaxEL-Coated
OAC Oral anticoagulant/ation Balloon Angioplasty Versus Drug-Eluting
OASIS-5 Fifth Organization to Assess Strategies in Acute Stenting in Acute Myocardial InfarcTION
Ischemic Syndromes RIVAL RadIal Vs femorAL access for coronary
OASIS-6 The Safety and Efficacy of Fondaparinux Versus intervention
Control Therapy in Patients With ST Segment ROMICAT II Multicenter Study to Rule Out Myocardial
Elevation Acute Myocardial Infarction Infarction by Cardiac Computed Tomography
OAT Occluded Artery Trial ROSC Return of spontaneous circulation
OCT Optical coherence tomography RR Relative risk
ODYSSEY Evaluation of Cardiovascular Outcomes After RV Right ventricular
OUTCOMES an Acute Coronary Syndrome During SAPT Single antiplatelet therapy
Treatment With Alirocumab SBP Systolic blood pressure
OHCA Out-of-hospital cardiac arrest s.c. Subcutaneous
OR Odds ratio SCAD Spontaneous coronary artery dissection
PARADISE-MI Prospective ARNI vs ACE Inhibitor Trial to SHOCK Should We Emergently Revascularize
Determine Superiority in Reducing Heart Occluded Coronaries for Cardiogenic Shock
Failure Events After MI SGLT2 Sodium–glucose co-transporter 2
PCI Percutaneous coronary intervention SMART-DECISION Long-term Beta-blocker Therapy After Acute
PCSK9 Proprotein convertase subtilisin/kexin type 9 Myocardial Infarction
PE Pulmonary embolism SPECT Single-photon emission computerized
PEGASUS-TIMI 54 PrEvention with TicaGrelor of SecondAry tomography
Thrombotic Events in High-RiSk Patients with STE ST elevation
Prior AcUte Coronary Syndrome— STEMI ST-elevation myocardial infarction
Thrombolysis In Myocardial Infarction STOPDAPT-2-ACS ShorT and OPtimal Duration of Dual
PEPCAD NSTEMI Bare Metal Stent Versus Drug Coated Balloon AntiPlatelet Therapy-2 Study for the Patients
With Provisional Stenting in Non-ST-Elevation With ACS
Myocardial Infarction STREAM Strategic Reperfusion Early After Myocardial
PLATO PLATelet inhibition and patient Outcomes Infarction
POC Point of care SWEDEHEART Swedish Web-System for Enhancement and
POPular Genetics Cost-effectiveness of CYP2C19 Genotype Development of Evidence-Based Care in Heart
Guided Treatment With Antiplatelet Drugs in Disease Evaluated According to
Patients With ST-segment-elevation Myocardial Recommended Therapies
Infarction Undergoing Immediate PCI With TALOS-AMI TicAgrelor Versus CLOpidogrel in Stabilized
Stent Implantation: Optimization of Treatment Patients With Acute Myocardial Infarction
PPCI Primary percutaneous coronary intervention TAT Triple antithrombotic therapy
ESC Guidelines 3727
TICO Ticagrelor Monotherapy After 3 Months in the The Members of this Task Force were selected by the ESC to
Patients Treated With New Generation represent professionals involved with the medical care of patients
Sirolimus Stent for Acute Coronary Syndrome with this pathology. The selection procedure aimed to include
TIMI Thrombolysis In Myocardial Infarction members from across the whole of the ESC region and from rele-
TLR Target lesion revascularization vant ESC Subspecialty Communities. Consideration was given to
TOMAHAWK Immediate Unselected Coronary Angiography diversity and inclusion, notably with respect to gender and country
Versus Delayed Triage in Survivors of of origin. The Task Force performed a critical evaluation of diag-
Out-of-hospital Cardiac Arrest Without nostic and therapeutic approaches, including assessment of the
ST-segment Elevation risk-benefit ratio. The strength of every recommendation and the
TOPIC Timing of Platelet Inhibition After Acute level of evidence supporting them were weighed and scored ac-
Coronary Syndrome cording to predefined scales as outlined below. The Task Force fol-
TOTAL Trial of routine aspiration ThrOmbecTomy lowed ESC voting procedures, and all approved recommendations
were subject to a vote and achieved at least 75% agreement among

with PCI vs. PCI ALone in patients with STEMI
TRITON-TIMI 38 TRial to Assess Improvement in Therapeutic voting members.
Outcomes by Optimizing Platelet InhibitioN The experts of the writing and reviewing panels provided declaration
with Prasugrel Thrombolysis In Myocardial of interest forms for all relationships that might be perceived as real or
Infarction 38 potential sources of conflicts of interest. Their declarations of interest
TROPICAL-ACS Testing Responsiveness to Platelet Inhibition were reviewed according to the ESC declaration of interest rules and
on Chronic Antiplatelet Treatment For Acute can be found on the ESC website (http://www.escardio.org/
Coronary Syndromes Guidelines) and have been compiled in a report published in a supple-
TTE Transthoracic echocardiography mentary document with the guidelines. The Task Force received its en-
TWILIGHT Ticagrelor With Aspirin or Alone in High-Risk tire financial support from the ESC without any involvement from the
Patients After Coronary Intervention healthcare industry.
UA Unstable angina The ESC Clinical Practice Guidelines (CPG) Committee supervises
UFH Unfractionated heparin and co-ordinates the preparation of new guidelines and is responsible
VA-ECMO Veno-arterial extracorporeal membrane for the approval process. ESC Guidelines undergo extensive review
oxygenation by the CPG Committee and external experts, including members
VALIANT VALsartan In Acute myocardial iNfarcTion from across the whole of the ESC region and from relevant ESC
VF Ventricular fibrillation Subspecialty Communities and National Cardiac Societies. After appro-
VKA Vitamin K antagonist priate revisions, the guidelines are signed off by all the experts involved
VT Ventricular tachycardia in the Task Force. The finalized document is signed off by the CPG
Committee for publication in the European Heart Journal. The guidelines
were developed after careful consideration of the scientific and medical
knowledge and the evidence available at the time of their writing. Tables
1. Preamble of evidence summarizing the findings of studies informing development
Guidelines evaluate and summarize available evidence with the aim of as- of the guidelines are included. The ESC warns readers that the technical
sisting health professionals in proposing the best diagnostic or therapeut- language may be misinterpreted and declines any responsibility in this
ic approach for an individual patient with a given condition. Guidelines are respect.
intended for use by health professionals and the European Society of Off-label use of medication may be presented in this guideline if a
Cardiology (ESC) makes its Guidelines freely available. sufficient level of evidence shows that it can be considered medically ap-
ESC Guidelines do not override the individual responsibility of health propriate for a given condition. However, the final decisions concerning
professionals to make appropriate and accurate decisions in consider- an individual patient must be made by the responsible health profes-
ation of each patient’s health condition and in consultation with that pa- sional giving special consideration to:
tient or the patient’s caregiver where appropriate and/or necessary. It is
also the health professional’s responsibility to verify the rules and reg- • The specific situation of the patient. Unless otherwise provided for
ulations applicable in each country to drugs and devices at the time of by national regulations, off-label use of medication should be limited
prescription, and, where appropriate, to respect the ethical rules of to situations where it is in the patient’s interest with regard to the
their profession. quality, safety, and efficacy of care, and only after the patient has
ESC Guidelines represent the official position of the ESC on a given been informed and has provided consent.
topic and are regularly updated. ESC Policies and Procedures for for- • Country-specific health regulations, indications by governmental
mulating and issuing ESC Guidelines can be found on the ESC website drug regulatory agencies, and the ethical rules to which health profes-
(https://www.escardio.org/Guidelines). sionals are subject, where applicable.
3728 ESC Guidelines
Table 1 Classes of recommendations
Definition Wording to use

Classes of recommendations
Class I Evidence and/or general agreement Is recommended or is indicated

that a given treatment or procedure is
beneficial, useful, effective.
Class II Conflicting evidence and/or a divergence of opinion about the usefulness/

efficacy of the given treatment or procedure.

Class IIa Weight of evidence/opinion is in Should be considered
favour of usefulness/efficacy.
Class IIb Usefulness/efficacy is less well May be considered

established by evidence/opinion.
Class III Evidence or general agreement that the Is not recommended

given treatment or procedure is not
©ESC 2023
useful/effective, and in some cases
© ESC 2023
may be harmful.
Table 2 Levels of evidence
Level of Data derived from multiple randomized clinical trials

evidence A or meta-analyses.
Level of Data derived from a single randomized clinical trial

evidence B or large non-randomized studies.
Level of Consensus of opinion of the experts and/or small studies,

evidence C retrospective studies, registries.
©ESC 2023
© ESC 2023
2. Introduction
The major aspects of the management of patients with acute coronary
syndromes described in this European Society of Cardiology (ESC)
Guideline are summarized in Figure 1.
ESC Guidelines 3729
ACS encompasses a spectrum
Unstable angina NSTEMI STEMI
1 Think ‘A.C.S.’ at initial assessment

Abnormal Clinical Stable
ECG? context? patient?
2 Think invasive management

STEMI Very high-risk NSTE-ACS High-risk NSTE-ACS
OR
Primary PCI Fibrinolysis Immediate angiography ± PCI Early (<24 h) angiography

(If timely primary PCI not feasible) should be considered
3 Think antithrombotic therapy

Antiplatelet therapy AND Anticoagulant therapy
+ OR OR OR
Aspirin P2Y12 inhibitor UFH LMWH Bivalirudin Fondaparinux
4 Think revascularization
Based on clinical status, co-morbidities, Aim for complete Consider adjunctive tests
and disease complexity revascularization to guide revascularization
OR
PCI CABG Intravascular imaging Intravascular physiology
5 Think secondary prevention
Antithrombotic Lipid lowering Smoking Cardiac Risk factor Psychosocial

therapy therapy cessation rehabilitation management considerations
Figure 1 Central illustration. ACS, acute coronary syndrome; CABG, coronary artery bypass grafting; ECG, electrocardiogram; LMWH, low molecular-
weight heparin; NSTE-ACS, non-ST-elevation acute coronary syndrome; PCI, percutaneous coronary intervention; PPCI, primary percutaneous coronary
intervention; STEMI, ST-elevation myocardial infarction; UFH, unfractionated heparin. Patients with acute coronary syndrome (ACS) can initially present with
a wide variety of clinical signs and symptoms and it is important that there is a high degree of awareness of this amongst both the general public and healthcare
providers. If ACS is suspected, think ‘A.C.S.’ for the initial triage and assessment. This involves performing an electrocardiogram (ECG) to assess for
Abnormalities or evidence of ischaemia, taking a targeted clinical history to assess the clinical Context of the presentation, and carrying out a targeted clinical
examination to assess for clinical and haemodynamic Stability. Based on the initial assessment, the healthcare provider can decide whether immediate invasive
management is required. Patients with ST-elevation myocardial infarction (STEMI) require primary percutaneous coronary intervention (PPCI) (or fibrinoly-
sis if PPCI within 120 min is not feasible); patients with non-ST-elevation ACS (NSTE-ACS) with very high-risk features require immediate angiography ± PCI
if indicated; patients with NSTE-ACS and high-risk features should undergo inpatient angiography (angiography within 24 h should be considered). A com-
bination of antiplatelet and anticoagulant therapy is indicated acutely for patients with ACS. The majority of patients with ACS will eventually undergo re-
vascularization, most commonly with PCI. Once the final diagnosis of ACS has been established, it is important to implement measures to prevent recurrent
events and to optimize cardiovascular risk. This consists of medical therapy, lifestyle changes and cardiac rehabilitation, as well as consideration of psycho-
social factors.
3730 ESC Guidelines
2.1. Definitions | Acute coronary myocardial infarction (MI) is associated with cTn release and is
syndromes and myocardial infarction made based on the fourth universal definition of MI.1 UA is defined
as myocardial ischaemia at rest or on minimal exertion in the ab-
Acute coronary syndromes (ACS) encompass a spectrum of condi- sence of acute cardiomyocyte injury/necrosis. It is characterized by
tions that include patients presenting with recent changes in clinical specific clinical findings of prolonged (>20 min) angina at rest; new
symptoms or signs, with or without changes on 12-lead electrocardio- onset of severe angina; angina that is increasing in frequency, longer
gram (ECG) and with or without acute elevations in cardiac tropo- in duration, or lower in threshold; or angina that occurs after a re-
nin (cTn) concentrations (Figure 2). Patients presenting with cent episode of MI. ACS are associated with a broad range of clinical
suspected ACS may eventually receive a diagnosis of acute myocar- presentations, from patients who are symptom free at presentation
dial infarction (AMI) or unstable angina (UA). The diagnosis of to patients with ongoing chest discomfort/symptoms and patients

The ACS spectrum
Oligo/ Increasing chest Persistent chest Cardiogenic shock/ Cardiac

asymptomatic pain/symptoms pain/symptoms acute heart failure arrest
Clinical
presentation
Normal ST segment ST segment Malignant

depression elevation arrhythmia
ECG
findings
Working
NSTE-ACS STEMI
diagnosis
Non-elevated Rise and fall

hs-cTn
levels
Final Unstable
NSTEMI STEMI
diagnosis angina
Figure 2 The spectrum of clinical presentations, electrocardiographic findings, and high-sensitivity cardiac troponin levels in patients with acute coronary
syndrome. ACS, acute coronary syndrome; ECG, electrocardiogram; hs-cTn, high-sensitivity cardiac troponin; NSTE-ACS, non-ST-elevation acute coronary
syndrome; NSTEMI, non-ST-elevation myocardial infarction; STEMI, ST-elevation myocardial infarction.
ESC Guidelines 3731
with cardiac arrest, electrical/haemodynamic instability, or cardio- Table 3 Definitions of terms related to invasive strat-
genic shock (CS) (Figure 2). egy and reperfusion therapy commonly used in this
Patients presenting with suspected ACS are typically classified based document
on ECG at presentation for the purposes of initial management. After
Term Definition
this, patients can be further classified based on the presence or absence
of cardiac troponin elevation (once these results are available), as de- First medical contact (FMC) The time point when the patient is initially
monstrated in Figures 2 and 3. These features (ECG changes and cardiac assessed by a physician, paramedic, nurse,
troponin elevation) are important in the initial triage and diagnosis of or other trained emergency medical
patients with ACS, helping to risk stratify patients and guide the initial services worker who can obtain and
management strategy. However, after the acute management and sta- interpret the ECG and deliver initial
bilization phase, most aspects of the subsequent management strategy interventions (e.g. defibrillation). FMC can
are common to all patients with ACS (regardless of the initial ECG
be either in the pre-hospital setting or
pattern or the presence/absence of cardiac troponin elevation at

upon patient arrival at the hospital (e.g.
presentation) and can therefore be considered under a common
the emergency department)
pathway. A glossary of the terms related to invasive strategies and
STEMI diagnosis The time at which a patient with ischaemic
reperfusion therapy commonly used in this document, and their
associated definitions, is provided in Table 3. symptoms is interpreted as presenting
While they are closely related, it is important to recognize that ACS with ACS and ST-segment elevation (or
is not the same as MI.1 AMI is defined as cardiomyocyte necrosis in the ST-segment elevation equivalent)
clinical setting of acute myocardial ischaemia. This includes MI due to Primary PCIa Emergent PCI with balloon, stent, or
atherothrombotic events (Type 1 MI) and also other potential causes other approved device, performed on the
of myocardial ischaemia and myocyte necrosis (Type 2–5 MI) IRA without previous fibrinolytic
(Supplementary data online, Table S1). Myocardial injury is another treatment
distinct entity, used to describe troponin release due to mechanisms Primary PCI strategya Emergency coronary angiography and PCI
other than myocardial ischaemia and not meeting the criteria for MI of the IRA if indicated
outlined in Supplementary data online, Table S1. Myocardial injury Rescue PCIa Emergency PCI performed as soon as
can be acute or chronic depending on whether there is evidence of possible in cases of failed fibrinolytic
dynamic change in the elevated troponins on serial testing. Some
treatment
causes of myocardial injury include myocarditis, sepsis, takotsubo car-
Routine early PCI strategy Coronary angiography, with PCI of the
diomyopathy, heart valve disease, cardiac arrhythmias, and heart fail-
after fibrinolysisa IRA if indicated, performed between 2 h
ure (HF).
and 24 h after successful fibrinolysis
The focus of this guideline is largely centred on the management of
patients who will eventually receive a diagnosis of Type 1 MI. Pharmaco-invasive strategya Fibrinolysis combined with rescue PCI (in
However, at every stage of the management of patients presenting cases of failed fibrinolysis) or routine early
with ACS, physicians must carefully consider other differential diag- PCI strategy (in cases of successful
noses in their clinical assessment because they are common, asso- fibrinolysis)
ciated with different underlying pathological mechanisms, have Immediate invasive strategy Emergency coronary angiography (i.e. as
different prognoses, and frequently require different treatment ap- soon as possible) and PCI/CABG of the
proaches. More information is provided in the Supplementary IRA if indicated
data online. In general, detailed information regarding the results Early invasive strategy Early coronary angiography (<24 h from
of individual trials will not be provided in the main guideline. diagnosis of ACS) and PCI/CABG of the
However, where appropriate, this information is provided in the IRA if indicated
Supplementary data online evidence tables.
© ESC 2023
Selective invasive strategy Coronary angiography ± PCI/CABG
based on clinical assessment and/or
non-invasive testing
ACS, acute coronary syndrome; CABG, coronary artery bypass grafting; ECG,
electrocardiogram; IRA, infarct-related artery; PCI, percutaneous coronary intervention;
STE-ACS, ST-segment-elevation acute coronary syndrome.
a
CABG may also be indicated instead of PCI in certain circumstances.
3732 ESC Guidelines
Clinical presentation Working diagnosisa Further investigations Final diagnosisb
hs-cTn levels

STEMI
STEMI
ECG ± Angiography NSTEMI

If a patient has
signs/symptoms
suggestive of ACS, Unstable angina
NSTE-ACS
perform an ECG
within 10 min of FMC
± Imaging
Non-ACS diagnosis
Figure 3 Classification of patients presenting with suspected acute coronary syndrome: from a working to a final diagnosis. ACS, acute coronary syndrome;
ECG, electrocardiogram; FMC, first medical contact; hs-cTn, high-sensitivity cardiac troponin; MI, myocardial infarction; NSTE-ACS, non-ST-elevation acute
coronary syndrome; NSTEMI, non-ST-elevation myocardial infarction: STEMI, ST-elevation myocardial infarction. aThe working ACS diagnosis can be clas-
sified as STEMI or NSTE-ACS on the basis of available clinical information and ECG findings. This allows for initial triage and assessment. bThe final diagnosis is
based on symptoms, ECG and troponin for the diagnosis of MI as well as the results of other tests (i.e. imaging and/or angiography) to facilitate understanding
of the mechanism and subclassification of the type of MI. Patients initially assigned a working diagnosis of STEMI or NSTE-ACS may eventually receive a final
non-ACS diagnosis.
2.2. Epidemiology of acute coronary heart disease is the most common cause of CVD death, accounting
for 38% of all CVD deaths in females and 44% in males.3
syndromes
Cardiovascular disease (CVD) is the most common cause of mortality
and morbidity worldwide, with a substantial portion of this burden
borne by low- and middle-income countries.2,3 ACS is often the first 2.3. Number and breakdown of classes of
clinical manifestation of CVD. In 2019, there were an estimated 5.8 mil- recommendations
lion new cases of ischaemic heart disease in the 57 ESC member coun- The total number of recommendations in this guideline is 193. A sum-
tries.3 The median age-standardized incidence estimate per 100 000 mary of the recommendations according to Class of Recommendation
people was 293.3 (interquartile ratio 195.8–529.5). CVD remains the and Level of Evidence (LoE) is also provided. As per Class of
most common cause of death within ESC member countries, account- Recommendation, there were 106 Class I, 70 Class II, and 17 Class III
ing for just under 2.2 million deaths in females and just over 1.9 million recommendations. As per LoE, there were 56 LoE A, 64 LoE B, and
deaths in males in the most recent year of available data. Ischaemic 73 LoE C recommendations.
ESC Guidelines 3733
2.4. What is new
Table 4 New recommendations
Recommendations Classa Levelb
Recommendations for antiplatelet and anticoagulant therapy in acute coronary syndrome

If patients presenting with ACS stop DAPT to undergo coronary artery bypass grafting, it is recommended they resume DAPT after surgery
I C
for at least 12 months.
In older ACS patients, especially if HBR, clopidogrel as the P2Y12 receptor inhibitor may be considered. IIb B
Recommendations for alternative antithrombotic therapy regimens
In patients who are event-free after 3–6 months of DAPT and who are not high ischaemic risk, single antiplatelet therapy (preferably with a

IIa A
P2Y12 receptor inhibitor) should be considered.
P2Y12 inhibitor monotherapy may be considered as an alternative to aspirin monotherapy for long-term treatment. IIb A
In HBR patients, aspirin or P2Y12 receptor inhibitor monotherapy after 1 month of DAPT may be considered. IIb B
In patients requiring OAC, withdrawing antiplatelet therapy at 6 months while continuing OAC may be considered. IIb B
De-escalation of antiplatelet therapy in the first 30 days after an ACS event is not recommended. III B
Recommendations for cardiac arrest and out-of-hospital cardiac arrest
Evaluation of neurological prognosis (no earlier than 72 h after admission) is recommended in all comatose survivors after cardiac arrest. I C
Transport of patients with out-of-hospital cardiac arrest to a cardiac arrest centre according to local protocol should be considered. IIa C
Recommendations for technical aspects of invasive strategies
In patients with spontaneous coronary artery dissection, PCI is recommended only for patients with symptoms and signs of ongoing
I C
myocardial ischaemia, a large area of myocardium in jeopardy, and reduced antegrade flow.
Intravascular imaging should be considered to guide PCI. IIa A
Intravascular imaging (preferably optical coherence tomography) may be considered in patients with ambiguous culprit lesions. IIb C
Recommendations for multivessel disease in ACS patients presenting in cardiogenic shock
Staged PCI of non-IRA should be considered. IIa C
Recommendations for multivessel disease in haemodynamically stable STEMI patients undergoing primary PCI
It is recommended that PCI of the non-IRA is based on angiographic severity. I B
Invasive epicardial functional assessment of non-culprit segments of the IRA is not recommended during the index procedure. III C
Recommendations for acute coronary syndrome complications
Implantation of a permanent pacemaker is recommended when high-degree AV block does not resolve within a waiting period of at least 5
I C
days after MI.
Cardiac magnetic resonance imaging should be considered in patients with equivocal echocardiographic images or in cases of high clinical
IIa C
suspicion of LV thrombus.
Following an acute anterior MI, a contrast echocardiogram may be considered for the detection of LV thrombus if the apex is not well
IIb C
visualized on echocardiography.
In selected patients with high-degree AV block in the context of an anterior wall MI and acute heart failure, early device implantation (cardiac
IIb C
resynchronization therapy—defibrillator/pacemaker) may be considered.
In patients with recurrent life-threatening ventricular arrhythmias, sedation or general anaesthesia to reduce sympathetic drive may be
IIb C
considered.
Recommendations for acute coronary syndrome comorbid conditions
It is recommended to base the choice of long-term glucose-lowering treatment on the presence of comorbidities, including heart failure,
I A
chronic kidney disease, and obesity.
For frail older patients with comorbidities, a holistic approach is recommended to individualize interventional and pharmacological
I B
treatments after careful evaluation of the risks and benefits.
An invasive strategy is recommended in cancer patients presenting with high-risk ACS with expected survival ≥6 months. I B
A temporary interruption of cancer therapy is recommended in patients in whom the cancer therapy is suspected to be a contributing cause
I C
of ACS.
A conservative non-invasive strategy should be considered in ACS patients with poor cancer prognosis (i.e. with expected life survival <6
IIa C
months) and/or very high bleeding risk.
Aspirin is not recommended in cancer patients with a platelet count <10 000/μL. III C
Continued
3734 ESC Guidelines
Clopidogrel is not recommended in cancer patients with a platelet count <30 000/μL. III C
In ACS patients with cancer and <50 000/μL platelet count, prasugrel or ticagrelor are not recommended. III C
Recommendations for long-term management
It is recommended to intensify lipid-lowering therapy during the index ACS hospitalization for patients who were on lipid-lowering therapy
I C
before admission.
Low-dose colchicine (0.5 mg once a day) may be considered, particularly if other risk factors are insufficiently controlled or if recurrent
IIb A
cardiovascular disease events occur under optimal therapy.
Combination therapy with a high-dose statin plus ezetimibe may be considered during index hospitalization. IIb B
Recommendations for patient perspectives in acute coronary syndrome care
Patient-centred care is recommended by assessing and adhering to individual patient preferences, needs and beliefs, ensuring that patient
I B
values are used to inform all clinical decisions.

It is recommended to include ACS patients in decision-making (as much as their condition allows) and to inform them about the risk of
I B
adverse events, radiation exposure, and alternative options. Decision aids should be used to facilitate the discussion.
It is recommended to assess symptoms using methods that help patients to describe their experience. I C
Use of the ‘teach back’ technique for decision support during the securing of informed consent should be considered. IIa B
Patient discharge information should be provided in both written and verbal formats prior to discharge. Adequate preparation and
education for patient discharge using the teach back technique and/or motivational interviewing, giving information in chunks, and checking IIa B
© ESC 2023
for understanding, should be considered.
Assessment of mental well-being using a validated tool and onward psychological referral when appropriate should be considered. IIa B
ACS, acute coronary syndrome; AV, atrioventricular; DAPT, dual antiplatelet therapy; HBR, high bleeding risk; IRA, infarct-related artery; LV, left ventricular(cle); MI, myocardial infarction;
OAC, oral anticoagulant/ation; PCI, percutaneous coronary intervention; STEMI, ST-elevation myocardial infarction.
a
Class of recommendation.
b
Level of evidence.
Table 5 Revised recommendations
Recommendations in 2017 and 2020 versions Classa LoEb Recommendations in 2023 version Classa LoEb
Recommendations for imaging for patients with suspected NSTE-ACS

In patients with no recurrence of chest pain, normal ECG In patients with suspected ACS, non-elevated (or
findings, and normal levels of cardiac troponin (preferably uncertain) hs-cTn, no ECG changes and no recurrence of
high sensitivity), but still with suspected ACS, a pain, incorporating CCTA or a non-invasive stress
I B IIa A
non-invasive stress test (preferably with imaging) for imaging test as part of the initial workup should be
inducible ischaemia or CCTA is recommended before considered.
deciding on an invasive approach.
Recommendations for timing of invasive strategy in NSTE-ACS
An early invasive strategy within 24 h is recommended in An early invasive strategy within 24 h should be
patients with any of the following high-risk criteria: considered in patients with at least one of the following
• Diagnosis of NSTEMI suggested by the diagnostic high-risk criteria:
algorithm recommended in Section 3 • Confirmed diagnosis of NSTEMI based on current
I A IIa A
• Dynamic or presumably new contiguous ST/T-segment recommended ESC hs-cTn algorithms
changes suggesting ongoing ischaemia • Dynamic ST-segment or T wave changes
• Transient ST-segment elevation • Transient ST-segment elevation
• GRACE risk score >140. • GRACE risk score >140.
Recommendations for antiplatelet and anticoagulant therapy in STEMI
A potent P2Y12 inhibitor (prasugrel or ticagrelor), or Pre-treatment with a P2Y12 receptor inhibitor may be
clopidogrel if these are not available or are contraindicated, considered in patients undergoing a primary PCI strategy.
is recommended before (or at latest at the time of) PCI, and I A IIb B
maintained over 12 months, unless there are
contraindications such as excessive risk of bleeding.
Recommendations for long-term antithrombotic therapy
After stent implantation in patients undergoing a strategy In patients who are event-free after 3–6 months of DAPT
of DAPT, stopping aspirin after 3–6 months should be and who are not high ischaemic risk, SAPT (preferably
IIa A IIa A
considered, depending on the balance between the with a P2Y12 receptor inhibitor) should be considered.
ischaemic and bleeding risks.
Continued
ESC Guidelines 3735
Recommendations for cardiac arrest and out-of-hospital cardiac arrest

Delayed as opposed to immediate angiography should be Routine immediate angiography after resuscitated cardiac
considered among haemodynamically stable patients arrest is not recommended in haemodynamically stable
IIa B III A
without ST-segment elevation successfully resuscitated patients without persistent ST-segment elevation (or
after out-of-hospital cardiac arrest. equivalents).
Targeted temperature management (also called Temperature control (i.e. continuous monitoring of core
therapeutic hypothermia), aiming for a constant temperature and active prevention of fever [i.e. >37.7°C])
temperature between 32 and 36 C for at least 24 h, is is recommended after either out-of-hospital or in-hospital
I B I B
indicated in patients who remain unconscious after cardiac arrest for adults who remain unresponsive after
resuscitation from cardiac arrest (of presumed cardiac return of spontaneous circulation.
cause).

Recommendations for in-hospital management
When echocardiography is suboptimal/inconclusive, an When echocardiography is suboptimal/inconclusive,
alternative imaging method (CMR preferably) should be IIa C CMR imaging may be considered. IIb C
considered.
Recommendations for management of multivessel disease in haemodynamically stable STEMI patients undergoing primary PCI
Routine revascularization of non-IRA lesions should be Complete revascularization is recommended either
considered in STEMI patients with multivessel disease IIa A during the index PCI procedure or within 45 days. I A
before hospital discharge.
Recommendations for acute coronary syndrome comorbid conditions
Glucose-lowering therapy should be considered in ACS Glucose-lowering therapy should be considered in
© ESC 2023
patients with blood glucose >10 mmol/L (>180 mg/dL), patients with ACS with persistent hyperglycaemia, while
IIa B IIa C
with the target adapted to comorbidities, while episodes episodes of hypoglycaemia should be avoided.
of hypoglycaemia should be avoided.
ACS, acute coronary syndrome; CCTA, coronary computed tomography angiography; CMR, cardiac magnetic resonance; DAPT, dual antiplatelet therapy; ECG, electrocardiography/gram;
ESC European Society of Cardiology; GRACE, Global Registry of Acute Coronary Events; hs-cTn, high-sensitivity cardiac troponin; IRA, infarct-related artery; NSTE-ACS, non-ST-elevation
acute coronary syndrome; NSTEMI, non-ST-elevation myocardial infarction; PCI, percutaneous coronary intervention; SAPT, single antiplatelet therapy; STEMI, ST-elevation myocardial
infarction.
a
b
Level of evidence.
New/revised concepts prompting consideration of the clinical diagnosis of ACS and the initi-
ation of testing aligned with specific diagnostic algorithms (Figure 4).
• ACS should be considered a spectrum, which encompasses both
Chest pain descriptors should be classified as cardiac, possibly car-
non-ST-elevation (NSTE)-ACS and ST-elevation MI (STEMI).
diac, and likely non-cardiac. Further information on the suggested use
• A section on the management of ACS in patients with cancer is
of these terms is provided in the Supplementary data online. The use
provided.
of the descriptor ‘atypical’ should be avoided. Chest pain-equivalent
• A section on patient perspectives is provided.
symptoms include dyspnoea, epigastric pain, and pain in the left or right
arm or neck/jaw.
Misdiagnosis or delayed diagnosis is sometimes due to an incomplete
3. Triage and diagnosis history or difficulty in eliciting symptoms from the patient. In order to
understand the complexity of ACS-related symptomatology, careful
3.1. Clinical presentation and physical
history taking and comprehensive interaction with the patient are
examination crucial and may help to facilitate an early and accurate diagnosis.
3.1.1. Clinical presentation Further information is provided in the Supplementary data online, in-
Acute chest discomfort—which may be described as pain, pressure, cluding Figure S1, which outlines some of the most common symptoms
tightness, heaviness, or burning—is the leading presenting symptom of ACS in women and men.
3736 ESC Guidelines
ACS
presentation
ECG Physical examination Clinical history Vital signs hs-cTna levels
Initial A.C.S.

assessment
NSTE-ACS NSTE-ACS
STEMI
with very high-risk featuresb without very high-risk featuresb
Working
diagnosis
Immediate angiography ± Immediate angiography Consider angiography

PPCI or fibrinolysis if timely ± PCI within 24 h for NSTE-ACS
PPCI not feasible with high risk features
Early invasive
angiography
according to
patient risk PPCI ATT Fibrinolysis PCI ATT PCI ATT
Non-immediate Intravascular Non-invasive hs-cTna ECG

Echo
angiography imaging imaging levels monitoring
Further
investigations
Long-term Lifestyle Smoking

PCI CABG
medical therapy measures cessation
Further
management
Figure 4 An overview of the initial triage, management and investigation of patients who present with signs and symptoms potentially consistent with acute
coronary syndrome. ACS, acute coronary syndrome; ATT, antithrombotic therapy; CABG, coronary artery bypass grafting; ECG, electrocardiogram; hs-cTn,
high-sensitivity cardiac troponin; NSTE-ACS, non-ST-elevation acute coronary syndrome; PPCI, primary percutaneous coronary intervention; STEMI,
ST-elevation myocardial infarction. The ‘A.C.S.’ assessment is detailed in Figure 5. aResults of hs-cTn measurements are not required for the initial stratifi-
cation of ACS and the initial emergency management (i.e. for patients with a working diagnosis of STEMI or very high-risk NSTE-ACS) should not be delayed
based on this. bFor patients with NSTE-ACS with very high-risk features, immediate angiography is recommended. For patients with NSTE-ACS with high-
risk features, early invasive angiography (i.e. <24 h) should be considered and inpatient invasive angiography is recommended. See Recommendation Table 4
for details.
It is important that awareness of the symptoms associated with the public to seek urgent medical help. Continuous education, pro-
ACS is high among the general population, in particular red flag motion, and advocacy efforts are important to make sure that this
symptoms such as prolonged chest pain (>15 min) and/or recurrent information is as widely available as possible to the general
pain within 1 h, which should prompt patients or other members of population.
ESC Guidelines 3737
3.1.2. History taking and physical examination 3.2. Diagnostic tools | Electrocardiogram
Patients with suspected ACS present in a broad range of clinical scen- The resting 12-lead ECG is the first-line diagnostic tool in the assess-
arios, including in the community, at the emergency department (ED), ment of patients with suspected ACS. It is recommended that an
or in the inpatient setting. It is crucial to take a focused medical history ECG is obtained immediately upon FMC and interpreted by a qualified
and accurately characterize the presenting symptoms in order to emergency medical technician or physician within 10 min.4,5 It should
manage the patient via the appropriate care pathway as soon as be repeated as necessary, especially if symptoms have waned at FMC.
possible. Based on the initial ECG, patients with suspected ACS can be differen-
Prompt assessment of vital signs is recommended at first medical tiated into two working diagnoses:
contact (FMC), at the same time as acquisition of an initial ECG
(Figure 5). In patients presenting with suspected ACS, physical examin- • Patients with acute chest pain (or chest pain-equivalent
ation is recommended and is useful both to eliminate differential diag- signs/symptoms) and persistent ST-segment elevation
noses and to identify very high-risk and high-risk ACS features. This may (or ST-segment elevation equivalents) on ECG (working

be particularly relevant for patients presenting with cardiac arrest, signs diagnosis: ST-segment elevation MI: STEMI). The vast major-
of CS, and/or haemodynamic or electrical instability.4 Focused physical ity of these patients will sustain myocardial necrosis and troponin ele-
examination should include checking for the presence of all major vation, fulfilling the criteria for an MI, but MI will not be the final
pulses, measurement of blood pressure in both arms, auscultation of diagnosis in all patients with a working diagnosis of STEMI.
the heart and lungs, and assessing for signs of HF or circulatory • Patients with acute chest pain (or chest pain-equivalent
compromise. signs/symptoms) but without persistent ST-segment
A C S
Abnormal Clinical Stable
ECG? context? patient?
Perform an ECG to assess Consider the clinical Perform an exam to assess

for evidence of ischaemia context and available if the patient is clinically
or other abnormalities investigations and vitally stable
Figure 5 The A.C.S. assessment for the initial evaluation of patients with suspected acute coronary syndrome. ECG, electrocardiogram. This figure sum-
marizes the initial ‘A.C.S. assessment’ that can be performed for a patient presenting with suspected ACS. ‘A’ stands for ‘Abnormal ECG?’: an ECG should be
performed within 10 min of FMC and assessed for evidence of abnormalities or ischaemia. ‘C’ stands for ‘Clinical Context?’: it is important to consider the
clinical context of the patient’s presentation and the results of any investigations that are available. This should also include a targeted history with the aim of
determining the patient’s symptoms and elucidating any other relevant background information. ‘S’ stands for ‘Stable Patient?’: the patient should be quickly
assessed to determine if they are clinically stable—this should include assessment of the clinical vital signs, including heart rate, blood pressure, and oxygen
saturations, if possible, as well as checking for potential signs of CS.
3738 ESC Guidelines
elevation (or ST-segment elevation equivalents) on ECG in aVR and/or V1, suggests multivessel ischaemia or left main coronary
(working diagnosis: non-ST-elevation [NSTE]-ACS). artery obstruction, particularly if the patient presents with haemo-
These patients may exhibit other ECG alterations, including transient dynamic compromise.9–11
ST-segment elevation, persistent or transient ST-segment depres- Bundle branch block (BBB). In patients with a high clinical sus-
sion, and T wave abnormalities, including hyperacute T waves, T picion of ongoing myocardial ischaemia, the presence of LBBB, right
wave inversion, biphasic T waves, flat T waves, and pseudo- bundle branch block (RBBB), or a paced rhythm precludes an accurate
normalization of T waves. Alternatively, the ECG may be normal. assessment of the presence or absence of ST-segment elevation.
The majority of patients in this category who subsequently display Therefore, patients presenting with these ECG patterns in combination
a typical rise and fall in cardiac troponin levels (i.e. fulfilling MI criteria with signs/symptoms that are highly suspicious for ongoing myocardial
as per the fourth universal definition of MI) will receive a final diagno- ischaemia should be managed similarly to those with clear ST-segment
sis of non-ST-elevation MI (NSTEMI). In other patients, the troponin elevation, regardless of whether the BBB is previously known (see
level will remain below the 99th centile and they will receive a final Supplementary data online).4
diagnosis of UA, although with high-sensitivity troponin assays this

diagnosis has become less common. It is also important to recognize 3.2.2. Acute coronary syndrome without persistent
that NSTEMI or UA will not be the final diagnosis in all patients with ST-segment elevation (non-ST elevation acute
an initial working diagnosis of NSTE-ACS. coronary syndrome)
While the ECG in the setting of NSTE-ACS may be normal in more
than one-third of patients, characteristic ECG abnormalities are fre-
3.2.1. Acute coronary syndrome with persistent quently present and increase the diagnostic probability of ACS.12–16
ST-segment elevation (suspected ST-elevation These ECG abnormalities include ST depression and T wave changes
myocardial infarction) (especially biphasic T waves or prominent negative T waves
The priority for these patients is the implementation of reperfusion ther- [Wellens’ sign, related to severe proximal left anterior descending ar-
apy as soon as possible (see Section 5). In the appropriate clinical context, tery stenosis]), (see Supplementary data online, Figure S3).
ST-segment elevation (measured at the J-point) is considered suggestive
of ongoing coronary artery acute occlusion in the following cases:
New ST elevation at the J-point in at least two contiguous leads: Recommendation Table 1 — Recommendations for
clinical and diagnostic tools for patients with suspected
• ≥2.5 mm in men <40 years, ≥2 mm in men ≥40 years, or ≥1.5 mm acute coronary syndrome
in women regardless of age in leads V2–V3
• and/or ≥1 mm in the other leads (in the absence of left ventricular Recommendations Classa Levelb
[LV] hypertrophy or left bundle branch block [LBBB]). It is recommended to base the diagnosis and initial
short-term risk stratification of ACS on a
In patients with suspected inferior STEMI, it is recommended to re- I B
combination of clinical history, symptoms, vital signs,
cord right precordial leads (V3R and V4R) in order to assess for
other physical findings, ECG, and hs-cTn.1,17,18
ST-segment elevation.6 Posterior leads (V7–V9) can also be recorded
to investigate for posterior STEMI, particularly in patients with ongoing ECG
symptoms and an inconclusive standard 12-lead ECG. Twelve-lead ECG recording and interpretation is
The diagnosis of ongoing acute coronary artery occlusion on ECG recommended as soon as possible at the point of I B
can sometimes be challenging, and some cases may warrant prompt FMC, with a target of <10 min.5,19
management and triage for immediate reperfusion therapy despite Continuous ECG monitoring and the availability of
the absence of ST-segment elevation. It is also important to recognize defibrillator capacity is recommended as soon as
that while the most sensitive sign for ongoing acute coronary possible in all patients with suspected STEMI, in I B
artery occlusion is ST-segment elevation, there are other ECG find- suspected ACS with other ECG changes or ongoing
ings that can be suggestive of ongoing coronary artery occlusion (or
chest pain, and once the diagnosis of MI is made.20,21
severe ischaemia). If these findings are present, prompt triage for
The use of additional ECG leads (V3R, V4R, and V7–
immediate reperfusion therapy is indicated (see Supplementary data
V9) is recommended in cases of inferior STEMI or if
online, Figure S2). I B
total vessel occlusion is suspected and standard leads
ST-segment depression in leads V1–V3 (especially when the terminal
are inconclusive.22–24
T wave is positive) and/or ST-segment elevation in V7–V9 are highly
suggestive of posterior coronary artery occlusion (often the left cir- An additional 12-lead ECG is recommended in cases
I C
cumflex artery).1,7 ST-segment elevation in V3R and V4R is highly sug- with recurrent symptoms or diagnostic uncertainty.
gestive of ongoing RV ischaemia.8 ST depression ≥1 mm in ≥6 surface Continued
leads (inferolateral ST depression), coupled with ST-segment elevation
ESC Guidelines 3739
Blood sampling Some of the clinical implications of hs-cTn assays are detailed in
Supplementary data online, Table S2.
It is recommended to measure cardiac troponins
It is also important to consider that there are other clinical conditions
with high-sensitivity assays immediately after
I B apart from Type 1 MI in which elevations in cTn can be observed (see
presentation and to obtain the results within 60 min
Supplementary data online, Section 3.3.1 and Table S3).
of blood sampling.15,25–27
It is recommended to use an ESC algorithmic
3.3.2. Central laboratory vs. point of care
approach with serial hs-cTn measurements (0 h/1 h I B
The vast majority of cTn assays that run on automated platforms in the
or 0 h/2 h) to rule in and rule out NSTEMI.28–44
central laboratory are sensitive (i.e. allow for the detection of cTn in
Additional testing after 3 h is recommended if the ∼20–50% of healthy individuals) or high-sensitivity (i.e. allow for the de-
first two hs-cTn measurements of the 0 h/1 h tection of cTn in ∼50–95% of healthy individuals) assays.
algorithm are inconclusive and no alternative I B High-sensitivity assays are recommended over lower-sensitivity assays,

diagnoses explaining the condition have been as they provide higher diagnostic accuracy at an identical low
made.45,46 cost.1,12,15,25–27,57,63
The use of established risk scores (e.g. GRACE risk The majority of currently used point-of-care (POC) tests cannot be
score) for prognosis estimation should be IIa B considered high-sensitivity assays.64 The advantage of POC tests is a
considered.47–49 shorter turnaround time. However, this is counterbalanced by lower
Triage for emergency reperfusion strategy sensitivity, lower diagnostic accuracy, and lower negative predictive va-
lue (NPV). A randomized trial in low-risk chest pain patients with sus-
© ESC 2023
It is recommended that patients with suspected
pected NSTE-ACS and onset of symptoms ≥2 h before ambulance
STEMI are immediately triaged for an emergency I A
50–52
presentation reported that the use of a pre-hospital rule-out strategy
reperfusion strategy. (with a single POC conventional troponin T test) resulted in a signifi-
ACS, acute coronary syndrome; ECG, electrocardiogram; ESC, European Society of cant reduction of 30-day healthcare costs and a comparable major ad-
Cardiology; FMC, first medical contact; GRACE, Global Registry of Acute Coronary verse cardiovascular event (MACE) rate in comparison to an ED
Events; hs-cTn, high-sensitivity cardiac troponin; MI, myocardial infarction; NSTEMI, rule-out strategy (with evaluation as per standard local practice).65
non-ST-elevation myocardial infarction; STEMI, ST-elevation myocardial infarction.
a
Class of recommendation. Overall, automated assays have been more thoroughly evaluated
b
Level of evidence. than POC tests and are currently preferred.1,12–15,26,34,35,53,55–58
However, this is a rapidly developing field and it will be important to
re-evaluate this preference when more extensively validated high-
sensitivity POC tests are clinically available.66–68
3.3. Diagnostic tools | Biomarkers 3.3.3. Confounders of cardiac troponin concentration

3.3.1. High-sensitivity cardiac troponins In patients presenting with suspected NSTE-ACS, four clinical variables
After excluding clinical and ECG signs suggestive of STEMI or very high- affect hs-cTn concentrations beyond the presence or absence of MI.
risk NSTE-ACS, biomarkers play a complementary role in the diagnosis, These variables are: age (concentrations in healthy very young vs.
risk stratification, and management of patients with suspected ACS. ‘healthy’ very old individuals differ by up to 300%); renal dysfunction
Measurement of a biomarker of cardiomyocyte injury, preferably high- (differences between otherwise healthy patients with very high vs.
sensitivity cardiac troponin (hs-cTn), is recommended in all patients very low estimated glomerular filtration rate [eGFR] of up to 300%);
with suspected ACS.15,17,25–27,53,54 If the clinical presentation is com- time from chest pain onset (>300%); and, to a lesser extent, sex
patible with myocardial ischaemia, then a rise and/or fall in cTn above (≈40%).28,34,35,69–76 Despite the potential baseline differences in
the 99th percentile of healthy individuals points to a diagnosis of MI hs-cTn values based on these four variables, absolute changes in
as per the criteria in the fourth universal definition of MI.1 In patients hs-cTn levels are still of diagnostic and prognostic value. Current data
with MI, levels of cTn rise rapidly (i.e. usually within 1 h if using high- on the use of sex-specific hs-cTn values in the diagnosis of MI have
sensitivity assays) after symptom onset and remain elevated for a vari- been controversial and failed to demonstrate a clear clinical bene-
able period of time (usually several days).1,15,26,53,55–58 fit.74,75,77–80 Therefore, until automated tools (i.e. risk assessment cal-
Advances in technology have led to a refinement in cTn assays and culators) incorporating the effect of all four clinical variables (age,
have improved their accuracy in detecting and quantifying cardiomyo- eGFR, time from chest pain onset, and sex) are available, the use of uni-
cyte injury.1,12–15,18,26,34,35,53,55–60 Data from large multicentre studies form cut-off concentrations should remain the standard of care for the
have consistently shown that hs-cTn assays increase diagnostic accuracy early diagnosis of MI.28,30,31,34,35,73,81,82
for MI at the time of presentation in comparison to conventional assays,
especially in patients presenting early after chest pain onset, enabling 3.3.4. Rapid ‘rule-in’ and ‘rule-out’ algorithms
more rapid ‘rule-in’ and ‘rule-out’ of MI.1,12–15,26,34,35,53,55–58 Overall, Due to their higher sensitivity and diagnostic accuracy for the detection
hs-cTn T and hs-cTn I subunit assays appear to provide comparable of MI at presentation, the time interval to the second cTn assessment
diagnostic accuracy in the early diagnosis of MI.28,32,61,62 The use of can be shortened with the use of hs-cTn assays. This substantially re-
the terms ‘normal’ and ‘abnormal’ to describe hs-cTn levels should duces the delay to diagnosis, translating into shorter stays in the ED,
be avoided; instead, the terms ‘non-elevated’ and ‘elevated’ should be lower costs, and less diagnostic uncertainty for patients.15,83–88 It is re-
used to refer to hs-cTn levels below and above the 99th percentile. commended to use the 0 h/1 h algorithm (best option) or the 0 h/2 h
3740 ESC Guidelines
algorithm (second-best option) (Figure 6). These algorithms have been ‘rule-in’ pathway patients with diagnoses other than MI still have condi-
derived and validated in large multicentre diagnostic studies using cen- tions that require specialist cardiology input and either coronary angi-
tral adjudication of the final diagnosis for all currently available hs-cTn ography or non-invasive imaging in order to establish an accurate
assays.27–39,62,70,73,82,89–93 Optimal thresholds for rule-out were se- final diagnosis.28,30,31,34,35,73,82 Therefore, the vast majority of patients
lected to allow a sensitivity and NPV of at least 99%. Optimal thresholds triaged towards the ‘rule-in’ pathway by these algorithms will require
for rule-in were selected to allow a positive predictive value (PPV) of at hospital admission and invasive coronary angiography (ICA).
least 70%. These algorithms were developed from large derivation co-
horts and then validated in large independent validation cohorts. The
previous ESC 0 h/3 h algorithm was considered as an alternative,40,56 3.3.4.1.3. Observe. Patients who do not qualify for the ‘rule-out’ or
but three recent large diagnostic studies suggested that the ESC 0 h/ ‘rule-in’ pathways are assigned to the ‘observe’ pathway. These patients re-
3 h algorithm appears to balance efficacy and safety less well than present a heterogeneous group and have been shown to have a mortality
more rapid protocols using lower rule-out concentrations, including rate that is comparable to rule-in patients.98 Therefore, an individual as-
the ESC 0 h/1 h algorithm.41–43 The very high safety and high efficacy sessment based on the particular risk profile of the patient (i.e. risk scores)

of applying the ESC 0 h/1 h algorithm was recently confirmed in three is of paramount importance for patients in this group. Additionally, a third
real-life implementation studies, including one randomized controlled measurement of cTn at 3 h (± echocardiography) is recommended as the
trial (RCT).44,94,95 Therefore, the ESC 0 h/3 h algorithm is an alternative next step in order to guide further management.45,46
for cases where the ESC 0 h/1 h or 0 h/2 h algorithms are not available. Most patients in the observe zone with a high degree of clinical
Of note, patients assigned to the ‘rule-out’ pathway using the ESC 0 h/ suspicion of ACS (e.g. relevant increase in cTn from presentation
1 h or 0 h/2 h algorithms have a very low rate of clinical events through to 3 h) are candidates for ICA. Conversely, most patients with a
to 30 days.95,96 low to intermediate likelihood for ACS according to clinical judg-
ment are candidates for non-invasive imaging after transfer from
the ED to the ward. Computed tomography (CT) angiography can
3.3.4.1. European Society of Cardiology 0 h/1 h and 0 h/2 h
be used to aid diagnosis and, in particular, to identify patients with
algorithms
non-obstructed coronary arteries who can be discharged if other
The ESC 0 h/1 h and 0 h/2 h algorithms are based on two underlying relevant diseases have been excluded. CT angiography can also iden-
concepts: firstly, hs-cTn is a continuous variable and the probability tify patients with obstructive coronary disease in whom revascular-
of MI increases with increasing hs-cTn values.28,30,31,34,35,73,82 ization may be considered. In the appropriate clinical context, if
Secondly, early absolute changes in the levels within 1 h or 2 h can be alternative conditions have been identified that explain the cTn va-
used as surrogates for absolute changes over 3 h or 6 h and provide in- lues (i.e. rapid ventricular rate response to atrial fibrillation [AF],
cremental diagnostic value to the single cTn assessment at presenta- marked anaemia, or a hypertensive emergency), further diagnostic
tion.27,28,30,31,34,35,73,82,97 The cut-off concentrations within the 0 h/ testing (i.e. ICA) may not be required.
1 h and 0 h/2 h algorithms are assay specific (Supplementary data The same concepts apply to the 0 h/2 h algorithm. Cut-off levels for
online, Table S4).27,28,30,31,34,35,73,82 both the 0 h/1 h and 0 h/2 h algorithms are also assay specific, and these
cut-off levels are shown in Supplementary data online, Table S4.99
3.3.4.1.1. Rule-out. The NPV for MI in patients assigned to the The ESC 0 h/1 h and 0 h/2 h algorithms should always be integrated
‘rule-out’ pathway has exceeded 99% in several large validation with a detailed clinical assessment and a 12-lead ECG. Repeat blood
cohorts.28–30,34,35,73 Assignment to the rule-out pathway does not al- sampling is mandatory in cases where there is ongoing or recurrent
ways equal outpatient management. However, when used in conjunc- chest pain. Recently, artificial intelligence models that include serial
tion with clinical and ECG findings, the 0 h/1 h and 0 h/2 h algorithms hs-cTn measurements in conjunction with individual risk profiles have
will enable the identification of appropriate candidates for early dis- been proposed to be useful to facilitate a personalized diagnostic evalu-
charge and outpatient management. Even after the ruling out of MI, ation of patients with suspected MI. Similarly, risk-assessment models
elective non-invasive or invasive imaging may be appropriate according combining hs-cTn values at presentation and after early or late resam-
to clinical and risk assessment, and an alternative diagnosis to MI should pling have been developed to predict MI events during the first 30 days.
be identified. These models may facilitate alternative hs-cTn cut-offs based on the
balance between NPV and PPV best suited to individual clinical sites.27
3.3.4.1.2. Rule-in. The PPV for MI in patients meeting the ‘rule-in’ A diagnostic approach to the use of the ESC 0 h/1 h and 0 h/2 h algo-
pathway criteria in several studies has been ∼70–75%. Most of the rithms is shown in Figure 6.
ESC Guidelines 3741
Patient presents with a suspected NSTEMI and

without an indication for immediate invasive angiography

Take hs-cTn at 0 h and 1 h/2 h
Very low initial hs-cTna Patients who do not meet High initial hs-cTn
the criteria for either of OR
OR
the other two pathways
Low initial hs-cTn and no Increase in 1 h/2 h hs-cTn
increase in 1 h/2 h hs-cTn
Appropriate management can be determined

based on the hs-cTn levels and clinical situation
Rule-out pathway Observe pathway Rule-in pathway
Figure 6 The 0 h/1 h or 0 h/2 h rule-out and rule-in algorithms using high-sensitivity cardiac troponin assays in patients presenting to the emergency de-
partment with suspected NSTEMI and without an indication for immediate invasive angiography. hs-cTn, high-sensitivity cardiac troponin; NSTEMI,
non-ST-elevation myocardial infarction. Patients are classified into one of three pathways as per the results of their hs-cTn values at 0 h (time of initial blood
test) and 1 h or 2 h later. Patients with a very low initial hs-cTn value or patients with a low initial value and no 1 h/2 h change in hs-cTn are assigned to the
‘rule-out’ pathway. Patients with a high initial hs-cTn value or a 1 h/2 h change in hs-cTn are assigned to the ‘rule-in’ pathway. Patients who do not meet the
criteria for the rule-out or rule-in strategies are assigned to the ‘observe’ pathway, and these patients should have hs-cTn levels checked at 3 h ± echocar-
diography in order to decide on further management. Cut-offs are assay specific (see Supplementary material online, Table S4) and derived to meet
pre-defined criteria for sensitivity and specificity for NSTEMI. Potential management and testing options for each of the three strategies are provided in
the relevant sections of the main text.12–15,26,27,53,55–58,100,101 aOnly applicable if the chest pain onset was >3 h prior to the 0 h hs-cTn measurement.
3742 ESC Guidelines
3.3.4.2. Practical guidance on how to implement the European recommended. However, CCTA may provide added value in certain clin-
Society of Cardiology 0 h/1 h algorithm ical settings (i.e. for patients in the observe zone in whom cTn and ECG
In order to maximize the safety and feasibility of implementing the 0 h/ results remain inconclusive). A normal CCTA (ruling out both obstructive
1 h algorithm, blood samples for hs-cTn at 0 h and 1 h should be ob- and non-obstructive plaque) has a high NPV to exclude ACS and is asso-
tained irrespective of other clinical details and pending results (see ca- ciated with excellent clinical outcomes.
veats of using rapid algorithms in Supplementary data online, Section 3.3. The systematic use of CCTA in rule-out patients after hospital dis-
2.2). This may result in unnecessary cTn measurements in the ∼10– charge may identify the presence of obstructive or non-obstructive pla-
15% of patients with very low 0 h concentrations and chest pain onset que and guide preventative medical therapies.118 CCTA can also be
>3 h, but substantially facilitates the process and thereby further in- used to risk stratify selected low-risk NSTEMI patients. Such patients,
creases patient safety. Similarly, the 0 h blood sample should be ob- who are found to have normal coronary arteries, non-obstructive cor-
tained immediately after admission to the ED. onary disease, or distal obstructive disease, may then not require
ICA.119–121 Of note, the utility of CCTA may be limited in patients
with tachycardia, established coronary artery disease (CAD), previous

3.3.5. Other biomarkers
stents, or extensive coronary calcification.
The use of biomarkers other than cTn for the diagnosis of ACS is not
recommended (unless cTn is not available). Among the multitude of
additional biomarkers evaluated for the diagnosis of NSTEMI, only cre- 3.4.3. Cardiac magnetic resonance imaging with or
atine kinase myocardial band isoenzyme, myosin-binding protein C, and without stress testing
copeptin may have clinical relevance when used in combination with Cardiac magnetic resonance (CMR) imaging delineates cardiac struc-
(standard) cTn T/I, although in most clinical situations their incremental ture and function, and also has the ability to provide assessments of
value above and beyond cTn is limited.45,46,83,102–114 myocardial perfusion and the pattern of myocardial injury. CMR is
the imaging test of choice when poor echocardiographic windows pre-
3.4. Diagnostic tools | Non-invasive imaging clude diagnostic echocardiographic evaluation. CMR allows direct visu-
3.4.1. Echocardiography alization of infarcted regions, providing information on scarring and
In emergency rooms and chest pain units, transthoracic echocardiog- viability that can be differentiated from other forms of myocardial injury
raphy (TTE) performed or interpreted by trained healthcare profes- (e.g. myocarditis). CMR is therefore of particular clinical value in estab-
sionals should be routinely available. In cases of suspected ACS with lishing a diagnosis of AMI where there is diagnostic uncertainty. CMR
diagnostic uncertainty, TTE can be useful to identify signs suggestive of can also be useful in identifying the culprit vascular territory and in con-
ongoing ischaemia or prior MI. However, this should not result in rele- firming a diagnosis of myocarditis or takotsubo cardiomyopathy,
vant delays in transfer to the cardiac catheterization laboratory if there amongst other differentials. CMR is of particular value in establishing
is suspicion of an acute coronary artery occlusion. TTE can also be useful a diagnosis in patients presenting with a working diagnosis of myocardial
to suggest alternative aetiologies associated with chest pain (i.e. acute infarction with non-obstructive coronary arteries (MINOCA) following
aortic disease, RV signs in pulmonary embolism [PE]). All patients pre- invasive angiography and is the gold standard for the assessment of LV
senting with CS or haemodynamic instability should undergo emergency thrombus.
TTE to try to identify the underlying cause—in particular, to assess LV
and RV function and look for evidence of mechanical complications.
Recommendation Table 2 — Recommendations for
non-invasive imaging in the initial assessment of patients
3.4.2. Computed tomography with suspected acute coronary syndrome
Upon clinical presentation, CT is often the diagnostic tool of choice for
ruling out alternative potentially life-threatening differential diagnoses Recommendations Classa Levelb
of ACS, like PE or aortic dissection (this should be an ECG-gated con-
Emergency TTE is recommended in patients with
trast CT angiogram with full coverage of the thoracic aorta and the
suspected ACS presenting with cardiogenic shock or I C
proximal head and neck vessels). Generally, CT does not have a role
suspected mechanical complications.
in patients presenting with suspicion of ongoing acute coronary occlu-
sion, for whom emergency ICA is the priority. In patients with suspected ACS, non-elevated (or
Coronary CT angiography (CCTA) has been investigated in many trials uncertain) hs-cTn levels, no ECG changes and no
for the assessment of patients presenting to the ED with suspected recurrence of pain, incorporating CCTA or a IIa A
NSTE-ACS. However, trials investigating CCTA in the era of hs-cTn as- non-invasive stress imaging test as part of the initial
says may be of greater relevance for contemporary practice. The workup should be considered.116,122–127
BEACON (Better Evaluation of Acute Chest Pain with Coronary Emergency TTE should be considered at triage in
Computed Tomography Angiography) study showed no reduction of in- cases of diagnostic uncertainty but this should not
hospital duration of stay or hospital admission in the CCTA arm com- result in delays in transfer to the cardiac IIa C
pared with patients investigated with hs-cTn, with similar results to those catheterization laboratory if there is suspicion of an
observed in the ROMICAT II (Rule Out Myocardial Ischemia/Infarction by acute coronary artery occlusion.
© ESC 2023
Computer Assisted Tomography) and RAPID-CTCA (Rapid Assessment Routine, early CCTA in patients with suspected ACS
of Potential Ischaemic Heart Disease with CTCA) trials.115–117 In the lat- is not recommended.117
III B
ter study, a default approach using early non-invasive CCTA in patients
with suspected NSTE-ACS did not improve clinical outcomes at 1 year ACS, acute coronary syndrome; CCTA, coronary computed tomography angiography;
ECG, electrocardiogram; hs-cTn, high-sensitivity cardiac troponin; TTE, transthoracic
and was associated with a modest increase in the duration and cost of
echocardiography.
the hospital stay. A default approach using CCTA as the first-line imaging a
investigation in patients with suspected NSTE-ACS is therefore not b
Level of evidence.
ESC Guidelines 3743
Cardiac magnetic resonance can also assess myocardial perfusion 4.1.1. Time to treatment
with pharmacological stress. This can be used as an alternative to Time to treatment is vital for the care of patients triaged to the STEMI
CCTA in the assessment of patients in the observe zone following pathway. Components of the total ischaemic time, contributors to delays
ECG and hs-cTn assessments, particularly in those with advanced, es- in initial management, and the selection of reperfusion strategy for STEMI
tablished CAD, in whom assessments of myocardial perfusion and via- patients are shown in Figure 7. Treatment times reflect the efficiency and
bility may provide more useful information than CCTA. Some quality of care of a system taking care of patients with suspected STEMI.
additional information on CMR, single-photon emission computerized The multidisciplinary STEMI treatment pathway should be subject to
tomography (SPECT) perfusion imaging and stress echocardiography continuous clinical audit in order to assess the treatment times for indi-
is provided in the Supplementary data online. vidual patients and identify opportunities for healthcare improvement
Depending on local expertise and availability, other forms of stress through quality indicators (QIs). If projected QIs are not met, interven-
imaging (e.g. SPECT, nuclear, stress echo) can be used to assess patients tions are needed to improve the performance of the system.
in the observe zone. Recognition of ischaemic symptoms by individuals in the community

has pivotal importance in activation of the out-of-hospital pathway, and
3.5. Differential diagnosis for acute chest this is especially relevant to first responders without healthcare training.
The recommended action should be to contact the EMS rather than to
pain
self-present to an ED or primary care clinician.
Several cardiac and non-cardiac conditions that may mimic ACS should
The time from symptom onset to ‘first call for help’ is associated with
be considered in the differential diagnosis of acute chest pain as part of
socioeconomic factors and sex.128 In order to avoid delays through fail-
the clinical assessment. More information about the differential diagno-
ure to recognize and act on symptoms of a ‘heart attack’, community
sis of acute chest pain is provided in the sections on MINOCA and Type
education initiatives should target less well-served groups (i.e. those
2 MI and in the Supplementary data online, Table S5.
from deprived communities, ethnic minority groups) and use targeted
public health messaging (i.e. avoiding stereotyped messaging that under-
4. Initial measures for patients pins a negative bias based on sex, ethnicity, or social background, and
using language and images that will resonate with those groups).
presenting with suspected acute System delays are representative of the quality of care and it is recom-
coronary syndrome | Initial mended to measure these as QIs.
treatment 4.1.2. Healthcare systems and system delays

4.1. Pre-hospital logistics of care For patients with suspected STEMI, the system delay (the time from
when the patient contacts the healthcare system to reperfusion) is
Individuals experiencing acute chest pain in the community represent
amenable to improvement by organizational measures, whereas patient
an undifferentiated population, often presenting ad hoc to first med-
delay is multifactorial. System delay is a predictor of mortality in STEMI
ical responders in the pre-hospital setting. These patients should
patients treated with primary PCI (PPCI).129–131 When a working diag-
undergo immediate risk assessment and triage following local proto-
nosis of STEMI is made in the pre-hospital setting (EMS), immediate ac-
cols established within the emergency medical service (EMS)
tivation of the catheterization laboratory team reduces treatment
(Figures 7 and 8).
delays and mortality.132–136
If the first responding medical professional suspects ACS, a 12-lead
When a STEMI working diagnosis is made by the EMS in the pre-
ECG should be acquired and analysed as soon as possible. It is recom-
hospital setting and the patient is triaged for emergency invasive manage-
mended that all medical and paramedical personnel caring for ACS pa-
ment, they should bypass the ED and go straight to the catheterization
tients within the EMS setting have access to defibrillation equipment
laboratory. Bypassing the ED is associated with a significant saving in the
and are trained in basic cardiac life support. Patients with suspected
time from FMC to wire crossing and may be associated with improved
ACS are initially categorized on the basis of the 12-lead ECG and
survival.137–139 For patients presenting to a non-PCI centre with a sus-
triaged into two initial treatment pathways: (i) one for patients with
pected STEMI, the ‘door-in to door-out time’—defined as the duration
an ECG consistent with STEMI (persistent ST-segment elevation or
between arrival of the patient at the hospital to discharge of the patient
equivalent ECG patterns) (Figure 7); and (ii) one for patients without
in an ambulance ‘en route’ to the PCI centre—is also an important clinical
ST-segment elevation or equivalent ECG patterns (suspected
performance measure, and a door-in to door-out time of ≤30 min is re-
NSTE-ACS) (Figure 8). The initial ECG-guided risk stratification should
commended to expedite reperfusion therapy.140
also trigger treatment decisions in the pre-hospital setting, including the
choice of target hospital, and serve to determine the sequence of initial
investigations and interventions (including pharmacological), in particu- 4.1.3. Emergency medical services
lar, the timing of ICA. At a national level, an EMS with an easily recalled and well-publicised un-
An initial diagnosis of suspected STEMI portends a higher risk of im- ique medical dispatching number (112 for most European Union coun-
mediate, life-threatening complications (e.g. ventricular fibrillation tries) is important to speed-up system activation. Parallel circuits
[VF]). Accordingly, there is an indication for initiating an emergency re- for the referral and transport of patients with suspected STEMI that by-
perfusion strategy and direct transfer to a centre with 24/7 PCI capabil- pass the EMS should be avoided. The ambulance system plays a critical
ities. Patients who present with an ECG without ST-segment elevation role in the early management of patients with suspected STEMI, including
(or equivalent ECG patterns) but have ongoing ischaemic symptoms immediately establishing the initial diagnosis, triage, and treatment.129,141
should undergo pre-hospital triage in accordance with protocols for pa- Ambulances in the EMS must be equipped with ECG recorders, de-
tients in the STEMI pathway, since they also face immediate risks, in- fibrillators, telemetry devices, and at least one person trained in ad-
cluding ventricular arrhythmias. vanced life support. The quality of the care provided depends on the
3744 ESC Guidelines
training of the staff involved. Ambulance personnel must be trained to based on symptoms consistent with myocardial ischaemia and the signs
recognize ischaemic symptoms, administer oxygen when appropriate, on a 12-lead ECG (see Section 3.2). It is recommended to initiate ECG
secure intravenous (i.v.) access, effectively relieve pain, administer fi- monitoring as soon as possible in all patients with suspected ACS in or-
brinolysis when indicated, and provide basic life support.142 der to detect life-threatening arrhythmias and to allow prompt defibril-
Ambulance staff should record an ECG as soon as possible for diagnos- lation if indicated.
tic purposes and either interpret the ECG or transmit it so that it can be
reviewed by experienced staff to establish or refute a working diagnosis 4.2.2. Acute pharmacotherapy
of STEMI. Regular and structured training of ambulance staff is manda- 4.2.2.1. Oxygen
tory for a high-quality pre-hospital service. Oxygen supplementation is recommended in ACS patients with hypox-
aemia (oxygen saturations <90%). Oxygen supplementation in patients
4.1.4. General practitioners who are not hypoxic (oxygen saturations >90%) is not associated with
In some countries, primary care clinicians (general practitioners) play an clinical benefits and is therefore not recommended.148,149

important role in the early care of patients with suspected ACS and
may provide the FMC. Education and training of general practitioners 4.2.2.2. Nitrates
in emergency, pre-hospital care is essential for the delivery of optimal Sublingual nitrate may be helpful to relieve ischaemic symptoms.
pre-hospital care in this setting. The responsibilities of the primary However, a reduction in chest pain after nitroglycerine administra-
care clinicians may include diagnosis, activation of the EMS, risk stratifi- tion can be misleading and is not recommended as a diagnostic man-
cation, and initiation of pre-hospital treatment. However, in most set- oeuvre.150 In patients with an ECG compatible with ongoing STEMI
tings, consultation with a general practitioner instead of a direct call to and symptom relief after nitroglycerine administration, it is recom-
the EMS will increase the pre-hospital delay. Therefore, the public mended to obtain another 12-lead ECG. Complete normalization
should be educated to call the EMS directly rather than a primary of ST-segment elevation, along with relief of symptoms, after nitro-
care physician for symptoms suggestive of ACS. glycerine administration is suggestive of coronary spasm, with or
without associated MI. Nitrates should not be given to patients
4.1.5. Organization of ST-elevation myocardial with hypotension, marked bradycardia or tachycardia, RV infarction,
infarction treatment in networks known severe aortic stenosis, or phosphodiesterase 5 inhibitor use
It is recommended that a regional reperfusion strategy is established to within the previous 24–48 h.
maximize the efficiency of care for patients with a working diagnosis of
STEMI.143 The optimal treatment of patients with a working diagnosis 4.2.2.3. Pain relief
of STEMI should be based on the implementation of networks between Intravenous opioids (e.g. morphine 5–10 mg) should be considered for
hospitals with various levels of clinical service provision (the ‘hub and the relief of severe chest pain. Other forms of pain relief (e.g. nitrous
spoke’ model), linked by a prioritized and efficient ambulance service. oxide/oxygen plus i.v. acetaminophen/paracetamol) have been re-
A PCI centre is a multidisciplinary acute care centre that provides emer- ported to be inferior to morphine.151 However, morphine may en-
gency invasive management 24/7 for patients presenting with suspected hance nausea and vomiting and slow the gastrointestinal absorption
STEMI. This centre should also provide intensive care facilities, and of oral medicines, which may delay the onset of action of orally admi-
more advanced centres should offer cardio-thoracic services, advanced nistered antiplatelet therapy.152,153 Evidence from small-scale trials sug-
haemodynamic support, and surgery. gests that i.v. morphine may also reduce myocardial and microvascular
The goal of STEMI networks is to provide optimal care while minimizing damage when given to patients with ongoing acute coronary artery oc-
delays, thereby improving clinical outcomes. Cardiologists should actively clusion, though co-administration with metoclopramide appears to
collaborate with all stakeholders, particularly emergency physicians, in estab- negate this effect. Conversely, morphine has also been reported to re-
lishing such networks. The main features of such a network are detailed in duce antiplatelet activity after administration of ticagrelor, though this
Supplementary data online, Table S6. It is recommended that the EMS should effect was rescued by metoclopramide administration.154,155 The posi-
transport patients with a working diagnosis of STEMI to hospitals with a 24/7 tive effects of morphine on myocardial damage may potentially be re-
service for PCI, bypassing non-PCI-capable hospitals.144 Further information lated to reduced oxygen consumption as a result of decreased
on this topic is provided in the Supplementary data online. preload and negative inotropy and chronotropy.
Geographic areas where the expected transfer time to the primary Platelet inhibition induced by oral P2Y12 receptor antagonists may
PCI centre makes it impossible to routinely achieve the maximal allow- be delayed in patients with ongoing MI. Morphine may also further re-
able delays indicated in the recommendations should develop protocols duce absorption, delay the onset of action, and decrease the antipla-
for rapid fibrinolysis at the place of STEMI diagnosis, with the aim of telet effect of oral P2Y12 receptor inhibitors in MI patients, although
treatment within 10 min of FMC, followed by immediate transfer to this effect may vary between the different P2Y12 inhibitors.153,156–
a centre with 24/7 service for PCI. Such networks increase the propor- 158
Further research is ongoing in this area, but at present it should
tion of patients receiving reperfusion with the shortest possible treat- be noted that currently available clinical data have not demonstrated
ment delay.145–147 The quality of care, time delays, and patient any increase in the risk of adverse clinical outcomes as a result of any
outcomes should be measured and reported to the healthcare profes- interaction between morphine and antiplatelet agents in the setting of
sionals contributing to the EMS. ACS.159–161
4.2. Emergency care 4.2.2.4. Intravenous beta-blockers

4.2.1. Initial diagnosis and monitoring Few RCTs testing early i.v. beta-blockers have been performed in
Management of ACS starts from the point of FMC, when a working the era of invasive management for patients with a working diagnosis
diagnosis of ACS is established. The working diagnosis of ACS is usually of STEMI. Not all beta-blockers appear to exert the same
ESC Guidelines 3745
cardio-protective effect in the context of ongoing acute coronary oc- It is recommended that ambulance teams are trained
clusion, with metoprolol demonstrating the greatest protective effect and equipped to identify ECG patterns suggestive of
in experimental studies.162 Intravenous metoprolol is also the most acute coronary occlusion and to administer initial I C
widely tested beta-blocker in trials enrolling patients undergoing therapy, including defibrillation, and fibrinolysis when
PPCI.163,164 While the long-term clinical benefits associated with early applicable.142
i.v. metoprolol administration are not clear, it is safe when used in pa-
It is recommended that all hospitals and EMS
tients without signs of acute HF and has been consistently associated
© ESC 2023
participating in the care of patients with suspected
with a reduction in the incidence of VF and microvascular obstruction I C
STEMI record and audit delay times and work
(MVO).163–171 Based on these data, i.v. beta-blockers (preferably meto-
together to achieve and maintain quality targets.
prolol) should be considered at the time of presentation in patients
with a working diagnosis of STEMI undergoing PPCI with no signs of CCU, cardiac care unit; ECG, electrocardiogram; EMS, emergency medical services; ICU,
acute HF, a systolic blood pressure (SBP) >120 mmHg, and without intensive care unit; i.v., intravenous; PPCI, primary percutaneous coronary intervention;
SaO2, saturation of oxygen; SBP, systolic blood pressure; STEMI, ST-elevation myocardial
other contraindications.163–166,169 Administration of i.v. beta-blockers

infarction.
in patients with suspected NSTE-ACS has not been tested. a
b
Level of evidence.
5. Acute-phase management of
Recommendation Table 3 — Recommendations for the
initial management of patients with acute coronary patients with acute coronary
syndrome syndrome
Recommendations Classa Levelb 5.1. Selection of invasive strategy and
Hypoxia reperfusion therapy
Oxygen is recommended in patients with The definitions of the terms related to invasive strategy and reperfusion
I C therapy are presented in Table 3.
hypoxaemia (SaO2 <90%).
Depending on the initial assessment of the ECG, the clinical context
Routine oxygen is not recommended in patients
III A and haemodynamic stability, patients with suspected ACS should be
without hypoxaemia (SaO2 >90%).148,172
classified as either:
Symptoms
(i) Patients with a working diagnosis of STEMI. These patients should
Intravenous opioids should be considered to relieve
IIa C be triaged for immediate reperfusion therapy (i.e. a PPCI strategy
pain.
or fibrinolysis if PPCI is not possible within 120 min of diagnosis)
A mild tranquilizer should be considered in very (Figure 7).
IIa C
anxious patients. Or
Intravenous beta-blockers (ii) Patients with a working diagnosis of NSTE-ACS. For these patients:
Intravenous beta-blockers (preferably metoprolol) • An inpatient invasive strategy is recommended.
should be considered at the time of presentation in • An immediate invasive strategy is recommended when any very
patients undergoing PPCI with no signs of acute heart IIa A high-risk feature is present (Figure 8).
• An early (i.e. within 24 h) invasive strategy should be considered
failure, an SBP >120 mmHg, and no other
when any high-risk features are present (Figure 8).
contraindications.163–167,169
Pre-hospital logistics of care
5.2. Acute coronary syndrome managed
It is recommended that the pre-hospital
management of patients with a working diagnosis of
with invasive strategy
STEMI is based on regional networks designed to Invasive management strategies are time sensitive. It is recommended that
I B patients triaged to an immediate invasive strategy (those with high suspi-
deliver reperfusion therapy expeditiously and
cion of ongoing acute coronary artery occlusion [i.e. persistent
effectively, with efforts made to make PPCI available
ST-segment elevation or equivalents] or NSTE-ACS with any very high-
to as many patients as possible.145
risk characteristics) receive emergency angiography as soon as possible.
It is recommended that PPCI-capable centres deliver
High-risk NSTE-ACS patients (e.g. ruled in as NSTEMI as per the 0 h/1 h
a 24/7 service and are able to perform PPCI without I B
or 0 h/2 h ESC algorithms, with dynamic ST-segment or T wave changes,
delay.173,174 with transient ST-segment elevation, or with a Global Registry of Acute
It is recommended that patients transferred for PPCI Coronary Events [GRACE] risk score >140) should be considered for
bypass the emergency department and CCU/ICU an early invasive strategy (i.e. undergoing angiography within 24 h).
I B
and are transferred directly to the catheterization
laboratory.137,175–178 5.2.1. Primary percutaneous coronary intervention
It is recommended that EMS transfer patients with strategy for ST-elevation myocardial infarction
suspected STEMI to a PCI-capable centre, bypassing I C In patients with a working diagnosis of STEMI, a PPCI strategy (i.e. im-
non-PCI centres. mediate angiography and PCI as needed) is the preferred reperfusion
Continued strategy, provided it can be performed in a timely manner (i.e. within
3746 ESC Guidelines
120 min of the ECG-based diagnosis, Figure 7). RCTs have shown that if invasive angiography (i.e. within 2–24 h from the time of the lytic bolus
the delay to treatment is similar, PPCI is superior to fibrinolysis in reducing injection) (see Section 5.3).186
mortality, non-fatal reinfarction, and stroke.52,179 However, in some cir- Patients with a working diagnosis of STEMI who present to a
cumstances, PPCI is not an immediate option and fibrinolysis should be non-PCI centre should be immediately transferred to a PCI-capable
initiated expeditiously as part of a pharmaco-invasive strategy, provided centre (Figure 7) for a timely PPCI strategy. If PPCI is not feasible within
the patient has presented within 12 h of symptom onset (see Section 5.3). 120 min, patients should undergo immediate fibrinolysis followed by
There is a lack of contemporaneous data to inform the treatment delay transfer to a PCI centre without waiting for signs of reperfusion. For
limit at which the advantage of PCI over fibrinolysis is lost. For simplicity, an patients presenting after 12 h from symptom onset, a PPCI strategy
absolute time of 120 min from STEMI diagnosis to PCI-mediated reperfu- is preferred over fibrinolysis in all cases.
sion (i.e. wire crossing of the infarct-related artery [IRA]) rather than a rela- Emergency coronary artery bypass grafting (CABG) surgery should
tive PCI-related delay over fibrinolysis has been chosen. Given the be considered for patients with a patent IRA but with unsuitable anat-
recommended time interval of 10 min from STEMI diagnosis to administra- omy for PCI, and either a large myocardial area at jeopardy or with CS.
tion of a bolus of fibrinolytics (see below), the 120 min absolute time delay In patients with MI-related mechanical complications who require cor-

would correspond to a relative PCI-related delay in the range of 110– onary revascularization, CABG is recommended at the time of surgical
120 min. This is within the range of the times identified as the limit of delay repair. In STEMI patients with failed PCI or with an acute coronary oc-
below which PCI should be chosen in older studies and registries.176,180–184 clusion not amenable to PCI, emergency CABG is infrequently per-
For patients who undergo fibrinolysis, rescue PCI is indicated if fibrin- formed because the benefits of surgical revascularization in this
olysis fails (i.e. ST-segment resolution <50% within 60–90 min of fi- setting are less certain.185,187,188 Because there will be a delay to reper-
brinolytic administration) or in the presence of haemodynamic or fusion with CABG in this situation, the probability of myocardial salvage
electrical instability, worsening ischaemia, or persistent chest to a degree sufficient to impact on prognosis is considered low. In add-
pain.184,185 Patients with successful fibrinolysis should undergo early ition, the surgical risks of CABG in this setting may be elevated.
Total ischaemic time and Total Patient Patient

ischaemic self calls
sources of delay to reperfusion
time presents EMS
Onset of
Patient with symptoms of ACS and
symptoms ECG consistent with STEMI
Patient self presents Patient calls
to hospital EMS
Mode of or
FMC
PCI centre Non-PCI centre Ambulance
FMC or
location
PCI possible in <120 min?
YES NO
PPCI PPCI Fibrinolysis

strategy strategy strategy
Determine Aim: Aim: Aim:

therapeutic <60 min to <90 min to <10 min to
wire crossing wire crossing lytic bolus
strategy
Immediate transfer Immediate transfer
to PCI centre to PCI centre Reperfusion
for primary PCI after fibrinolysis
Patient delay
EMS delay
System delay
Total ischaemic time
Figure 7 Modes of presentation and pathways to invasive management and myocardial revascularization in patients presenting with STEMI. ACS, acute
coronary syndrome; ECG, electrocardiogram; EMS, emergency medical services; FMC, first medical contact; PCI, percutaneous coronary intervention;
PPCI, primary percutaneous coronary intervention; STEMI, ST-segment elevation myocardial infarction.
ESC Guidelines 3747
5.2.1.1. Invasive strategy in ST-elevation myocardial infarction late multivessel disease (MVD), improved co-adjuvant pharmacological
presenters therapies, and contemporary biomarker assays.
While routine immediate angiography and PCI (if indicated) are clearly
associated with clinical benefit in patients presenting within 12 h of 5.2.3.1. Early vs. delayed invasive strategy for non-ST elevation acute
symptom onset, the value of a routine PPCI strategy in STEMI patients coronary syndrome
presenting later than 12 h after symptom onset is less well established.
An early invasive strategy refers to routine invasive angiography (and
A small RCT in 347 STEMI patients presenting 12–48 h after symp-
PCI if needed) within 24 h of presentation. This should be considered
tom onset and without persistent symptoms reported that a routine
in patients with a working diagnosis of NSTE-ACS and any of the fol-
PPCI strategy improved myocardial salvage and long-term survival com-
lowing high-risk criteria:
pared with conservative treatment.189,190 This observation is supported
by a recent analysis of data from three nationwide observational studies • A confirmed diagnosis of NSTEMI based on current recommended
from the FAST-MI (French Registry of Acute ST-elevation and ESC hs-cTn algorithms.

non-ST-elevation Myocardial Infarction) programme, which showed a • Dynamic ST-segment or T wave changes.
significant lower rate of all-cause death at 1 month (2.1% vs. 7.2%) • Transient ST-segment elevation.
and after a median follow-up of 58 months (30.4% vs. 78.7%) with an in- • A GRACE risk score >140.
vasive strategy in comparison to conservative treatment.191 However, in
stable patients with persistent occlusion of the IRA 3–28 days after MI, Several meta-analyses have pooled data from multiple RCTs assessing
the large (n = 2166) Occluded Artery Trial (OAT) reported no clinical different timing intervals of invasive angiography among NSTE-ACS pa-
benefit from routine coronary intervention with medical management in tients. None of these studies observed superiority of early invasive strat-
comparison to medical management alone.192,193 A meta-analysis of egies compared with routine invasive strategies for death or non-fatal MI,
trials testing whether late recanalization of an occluded IRA is beneficial although early invasive strategies were associated with a lower risk
also showed no benefit of reperfusion.194 Therefore, routine PCI of an of recurrent/refractory ischaemia and a shorter duration of hospital
occluded IRA in STEMI patients presenting >48 h after onset of symp- stay.201–203 A collaborative meta-analysis comparing an early vs. a delayed
toms and without persistent symptoms is not indicated.192,193 These pa- invasive strategy using a modified individual patient data approach ob-
tients should be managed in the same way as patients with chronic total served no difference in mortality overall but a survival benefit in high-risk
occlusion according to the ESC Guidelines for the diagnosis and manage- patients, including those with a GRACE risk score >140 and those with
ment of chronic coronary syndromes (CCS).195 positive troponin, although tests for interaction were inconclusive.202
The largest meta-analysis to date (17 RCTs >10 000 patients) reported
that, in all-comers with NSTE-ACS, early ICA only significantly reduced
5.2.2. Immediate invasive strategy for non-ST
the risk of recurrent ischaemia and duration of stay, with no significant re-
elevation acute coronary syndrome
ductions in all-cause mortality, MI, admission for HF, or repeat revascular-
An immediate invasive strategy refers to emergency (i.e. as soon as pos- ization.203 The main limitation of the interpretation of meta-analyses of
sible) angiography and PCI if indicated. This is recommended for pa- these RCTs is the variability of the time to invasive angiography in the in-
tients with a working diagnosis of NSTE-ACS and any of the dividual trials: while invasive angiography was virtually always performed
following very high-risk criteria: within 24 h of randomization in the early invasive strategy groups, the
• Haemodynamic instability or CS. time from randomization to angiography was heterogeneous in the de-
• Recurrent or ongoing chest pain refractory to medical treatment. layed invasive groups. In many trials, delayed angiography was performed
• Acute HF presumed secondary to ongoing myocardial ischaemia. within 24 h of randomization (albeit later than in the early angiography
• Life-threatening arrhythmias or cardiac arrest after presentation. arm of the respective trial). Additionally, the diagnosis of NSTEMI was
• Mechanical complications. not based on the current recommended ESC hs-cTn algorithms.
• Recurrent dynamic ECG changes suggestive of ischaemia (particularly Moreover, studies assessing the value of a GRACE risk score >140 to
with intermittent ST-segment elevation). guide the timing of ICA and revascularization in the era of hs-cTn for
the diagnosis of NSTEMI are lacking. Further detail on the interaction be-
tween treatment effect according to GRACE score and its components in
5.2.3. Routine vs. selective invasive strategy individual trials is provided in the Supplementary data online. Data from
A routine invasive strategy with inpatient coronary angiography is re- observational studies is concordant with trial data, without a strong signal
commended for patients with a confirmed diagnosis of NSTEMI or a of benefit with early versus delayed coronary angiography.204
working diagnosis of NSTE-ACS and a high index of suspicion for A selective invasive approach after appropriate ischaemia testing or
UA. In patients with a working diagnosis of NSTE-ACS, multiple detection of obstructive CAD by CCTA is recommended in patients
RCTs comparing routine vs. selective invasive strategies have been without very high- or high-risk features and a low index of suspicion
conducted and their results have been pooled in several meta- for NSTE-ACS. These patients should be managed as per the ESC
analyses.196–200 The available evidence indicates that a routine invasive Guidelines for the management of CCS.195 A selective invasive ap-
strategy does not reduce all-cause mortality risk in the overall popula- proach is also appropriate for patients with NSTEMI or UA who are
tion of NSTE-ACS patients, but reduces the risk of composite ischae- not deemed good candidates for coronary angiography.
mic endpoints, particularly in high-risk patients. A routine invasive
strategy can increase the risk of peri-procedural complications and
bleeding. However, most of the available evidence is based on old 5.2.4. Summary of invasive strategies for patients
RCTs that were conducted before the implementation of several im- with non-ST elevation acute coronary syndrome
portant developments in PCI, including radial access, modern In summary, very high-risk NSTE-ACS patients are recommended to
drug-eluting stents (DES), complete functional revascularization for undergo an immediate invasive strategy with emergency angiography
3748 ESC Guidelines
FMC Patient with symptoms of ACS and ECG consistent with NSTE-ACS
Non-PCI centre Ambulance PCI centre
FMC or
location

Very high Immediate transfer Very high
riska risk
Haemodynamic instability or cardiogenic shock

Recurrent or ongoing chest pain refractory to medical treatment
Acute heart failure presumed secondary to ongoing myocardial ischaemia
Life-threatening arrhythmias or cardiac arrest after presentation
Mechanical complications
Recurrent dynamic ECG changes suggestive of ischaemia
Early/inpatient transfer
High riska High risk
Confirmed diagnosis of NSTEMI based on ESC algorithms

GRACE risk score >140
Transient ST-segment elevation
Dynamic ST-segment or T wave changes
Risk stratify Non-high Inpatient transfer Non-high

and determine risk (if required) risk
therapeutic
strategy In patients without very-high or
high-risk features and a low index Early (<24 h)
of suspicion for unstable angina invasive
strategy
(Class IIa)
Selective Inpatient Inpatient Immediate

invasive invasive invasive invasive
strategy strategy strategy strategy
(Class I) (Class I) (Class I) (Class I)
Figure 8 Selection of invasive strategy and reperfusion therapy in patients presenting with NSTE-ACS. ACS, acute coronary syndrome; CS, cardiogenic
shock; ECG, electrocardiogram; FMC, first medical contact; GRACE, Global Registry of Acute Coronary Events; hs-cTn, high-sensitivity cardiac troponin;
NSTE-ACS, non-ST-elevation acute coronary syndrome; NSTEMI, non-ST-elevation myocardial infarction; PCI, percutaneous coronary intervention; UA,
unstable angina. This figure summarizes the selection of invasive strategy and reperfusion therapy in patients presenting with ACS. aRisk criteria: Patients
who meet any one of the ‘very high-risk’ NSTE-ACS criteria should undergo an immediate invasive strategy; these very high-risk criteria include haemo-
dynamic instability or CS, recurrent or refractory chest pain despite medical treatment, life-threatening arrhythmias, mechanical complications of MI, HF
clearly related to ACS, and recurrent dynamic ST-segment or T wave changes, particularly with intermittent ST-segment elevation. Patients with
NSTE-ACS who meet any of the ‘high-risk’ criteria (confirmed NSTEMI as per the hs-cTn-based ESC algorithm, NSTE-ACS with GRACE score >140, dy-
namic ST-segment or T wave changes, or transient ST-segment elevation) should be considered for early invasive angiography (i.e. within 24 h) and should
undergo an inpatient invasive strategy. An invasive strategy during hospital admission is recommended in NSTE-ACS patients with high-risk criteria or with a
high index of suspicion for UA. In selected patients a selective invasive strategy can also be an option. See Recommendation Table 4 for full details.
and PCI if required. High-risk NSTE-ACS patients are recommended patients with clinical suspicion for NSTE-ACS and non-elevated tro-
to undergo an inpatient invasive strategy and should be considered ponins or patients with elevated troponins not meeting the criteria
for an early invasive strategy (i.e. within 24 h). For patients who do for MI), the strategy can be tailored based on the degree of clinical
not meet any of the very high-risk or high-risk criteria (generally suspicion. For patients with a high index of suspicion for UA, an
ESC Guidelines 3749
inpatient invasive strategy is recommended. Conversely, for patients trials have shown that routine early angiography with subsequent PCI
with a low index of suspicion, a selective invasive approach is (if required) after fibrinolysis reduced the rates of re-infarction and re-
recommended. current ischaemia in comparison to a ‘watchful waiting’ strategy (i.e. a
strategy in which angiography and revascularization were performed
5.3. Fibrinolysis and pharmaco-invasive only in patients with spontaneous or induced severe ischaemia or LV
dysfunction, or in patients with a positive outpatient ischaemia
strategy in patients with ST-elevation test).186,209,212–215 A network meta-analysis including 15 357 STEMI pa-
myocardial infarction tients treated with fibrinolytic therapy (n = 4212), PPCI (n = 6139), or
5.3.1. Benefit and indication of fibrinolysis fibrinolysis followed by routine immediate or early PCI (n = 5006) in-
Fibrinolytic therapy is an important reperfusion strategy for STEMI pa- vestigated whether STEMI patients should be transferred to a
tients presenting within 12 h of symptom onset when PPCI cannot be PCI-capable facility immediately (defined as a facilitated PCI approach)
performed in a timely manner; it prevents 30 early deaths per 1000 pa- or within a day (e.g. <24 h, defined as a pharmaco-invasive ap-
tients treated within 6 h of symptom onset.205 The largest absolute treat- proach).209 After PPCI, the pharmaco-invasive strategy was the second

ment benefit is seen among those patients at the highest risk, including the most favourable approach, with an odds ratio (OR) for death of 0.79
elderly. Successful reperfusion is generally associated with significant im- (95% confidence interval [CI], 0.59–1.08) compared with conventional
provement in ischaemic symptoms, ≥50% ST-segment resolution, fibrinolytic therapy. This supports the safety of transferring STEMI pa-
and haemodynamic stability. The doses of fibrinolytic agents and concomi- tients to a PCI-capable centre for angiography within 2–24 h. The bene-
tant antithrombotic therapies are given in the Fibrinolysis and Pharmaco- fit of routine early PCI after fibrinolysis was demonstrated without an
invasive Strategy provided in the Supplementary data online, Section 6.3. increased risk of adverse events (stroke or major bleeding), and across
the spectrum of the investigated patient subgroups.209,216 Therefore,
early angiography with subsequent PCI if required is the recommended
5.3.1.1. Pre-hospital fibrinolysis
standard of care after successful fibrinolysis (Figure 7). Observational
If trained medical or allied health staff can interpret the ECG on site, or
analysis of registry data has also provided some further support for
transmit the ECG for remote interpretation, it is recommended to ini-
the use of a pharmaco-invasive strategy.130
tiate fibrinolytic therapy in the pre-hospital setting. A fibrin-specific
The optimal time delay between successful fibrinolysis and PCI has
agent (i.e. tenecteplase, alteplase, or reteplase) is the preferred agent.
not been clearly defined; there has been a wide variation in this time
The goal is to start fibrinolytic therapy within 10 min of the STEMI diag-
delay in trials, ranging from a median of 1.3 to 17 h.184,185,206,215,217
nosis. Fibrinolytic therapy initiation should not be delayed by waiting for
Based on these data, a time window for PCI of 2–24 h after successful
the results of cardiac biomarker testing. In a meta-analysis of six rando-
lysis is recommended.
mized trials (n = 6434), pre-hospital fibrinolysis compared with in-
hospital fibrinolysis reduced early mortality by 17%, particularly when
5.3.1.2.1. Comparison of fibrinolytic agents. Some information on
administered in the first 2 h after symptom onset.51,206 These, and
comparisons of fibrinolytic agents is provided in the Supplementary
more recent, data support the pre-hospital initiation of fibrinolytic
data online, Section 6.3.1.
treatment when a reperfusion strategy is indicated.145,207–209 The
STREAM (Strategic Reperfusion Early After Myocardial Infarction) trial
demonstrated that pre-hospital fibrinolysis followed by an early PCI 5.3.1.2.2. Hazards of fibrinolysis and contraindications. Some infor-
strategy was associated with a similar outcome to transfer for PPCI mation regarding the hazards of, and contraindications to, fibrinolysis is
in STEMI patients presenting within 3 h of symptom onset who could provided in the Supplementary data online, Section 6.3.2.
not undergo PPCI within 1 h of FMC, although a slight excess of intra-
cranial bleeding was observed with the investigational strategy.184,210 5.4. Patients not undergoing reperfusion
This excess in intracranial bleeding was blunted by halving the dose The management of ACS patients not undergoing reperfusion is dis-
of tenecteplase in patients >75 years of age. cussed in the Supplementary data online, Section 5.2.
5.3.1.2. Angiography and percutaneous coronary intervention after 5.4.1. Patients who are not candidates for invasive
fibrinolysis (pharmaco-invasive strategy) coronary angiography
It is recommended that patients should be transferred to a PCI centre Information regarding the management of NSTE-ACS patients who are
immediately after initiation of lytic therapy (Figure 7). In cases of failed not candidates for invasive angiography is provided in the
fibrinolysis or evidence of re-occlusion or re-infarction with recurrence Supplementary data online, Section 5.2.1.
of ST-segment elevation, immediate angiography and rescue PCI are in-
dicated.185,211 In this setting, re-administration of fibrinolysis is not 5.4.2. Patients with coronary artery disease not
beneficial and is discouraged.185 Even if it is likely that fibrinolysis is suc- amenable to revascularization
cessful (e.g. ST-segment resolution >50% at 60–90 min; typical reper- Information regarding the management of ACS patients with CAD that
fusion arrhythmia; and disappearance of chest pain), routine early is not amenable to revascularization is provided in the Supplementary
angiography (i.e. within 2–24 h) is recommended. Several randomized data online, Section 5.2.2.
3750 ESC Guidelines
Recommendation Table 4 — Recommendations for re- Invasive strategy in NSTE-ACS

perfusion therapy and timing of invasive strategy
An invasive strategy during hospital admission is
Recommendations Classa Levelb recommended in NSTE-ACS patients with high-risk
I A
criteria or a high index of suspicion for unstable
Recommendations for reperfusion therapy for patients with angina.196–200
STEMI A selective invasive approach is recommended in
Reperfusion therapy is recommended in all patients patients without very high- or high-risk NSTE-ACS
I A
with a working diagnosis of STEMI (persistent criteria and with a low index of suspicion for
I A
ST-segment elevation or equivalentsc) and symptoms NSTE-ACS.196–200
of ischaemia of ≤12 h duration.51,182 An immediate invasive strategy is recommended in
A PPCI strategy is recommended over fibrinolysis if patients with a working diagnosis of NSTE-ACS and

the anticipated time from diagnosis to PCI is I A with at least one of the following very high-risk
<120 min.52,218,219 criteria:
If timely PPCI (<120 min) cannot be performed in • Haemodynamic instability or cardiogenic shock
patients with a working diagnosis of STEMI, • Recurrent or refractory chest pain despite medical
fibrinolytic therapy is recommended within 12 h of I A treatment I C
symptom onset in patients without • In-hospital life-threatening arrhythmias
contraindications.176,183 • Mechanical complications of MI
Rescue PCI is recommended for failed fibrinolysis • Acute heart failure presumed secondary to
(i.e. ST-segment resolution <50% within 60–90 min ongoing myocardial ischaemia
of fibrinolytic administration) or in the presence of I A • Recurrent dynamic ST-segment or T wave changes,
haemodynamic or electrical instability, worsening particularly intermittent ST-segment elevation.
ischaemia, or persistent chest pain.184,185 An early invasive strategy within 24 h should be
In patients with a working diagnosis of STEMI and a considered in patients with at least one of the
time from symptom onset >12 h, a PPCI strategy is following high-risk criteria:
recommended in the presence of ongoing symptoms I C • Confirmed diagnosis of NSTEMI based on current
IIa A
suggestive of ischaemia, haemodynamic instability, or recommended ESC hs-cTn algorithms
© ESC 2023
life-threatening arrhythmias.220 • Dynamic ST-segment or T wave changes
A routine PPCI strategy should be considered in • Transient ST-segment elevation
STEMI patients presenting late (12–48 h) after IIa B • GRACE risk score >140202,226–230
symptom onset.189–191,221 ACS, acute coronary syndrome; ECG, electrocardiogram; ESC, European Society of
Routine PCI of an occluded IRA is not recommended Cardiology; GRACE, Global Registry of Acute Coronary Events; hs-cTn, high-sensitivity
cardiac troponin; IRA, infarct-related artery; MI, myocardial infarction; NSTE-ACS,
in STEMI patients presenting >48 h after symptom III A
non-ST-elevation acute coronary syndrome; NSTEMI, non-ST-elevation myocardial
onset and without persistent symptoms.189,192,193 infarction; PPCI, primary percutaneous coronary intervention; STEMI, ST-elevation
myocardial infarction.
Transfer/interventions after fibrinolysis a
Transfer to a PCI-capable centre is recommended in b
Level of evidence.
c
all patients immediately after fibrinolysis.184– I A ST-segment elevation equivalents are presented in Supplementary data online, Figure S2.
186,212,213,222–224
Emergency angiography and PCI of the IRA, if

indicated are recommended in patients with
6. Antithrombotic therapy
I A
new-onset or persistent heart failure/shock after Antithrombotic treatment is an important component of the manage-
fibrinolysis.185,225 ment of all patients presenting with ACS. The specific choice and com-
Angiography and PCI of the IRA, if indicated, is bination of therapy, the time of its initiation, and the treatment duration
recommended between 2 and 24 h after successful I A depend on various patient and procedural factors. Treatment decisions
fibrinolysis.186,212,213,217,224 must be made weighing the benefits of antithrombotic therapy against
the risk of bleeding, including severe, life-threatening bleeding.231,232
Continued
Recommended anticoagulant and antiplatelet drugs and their dosing
(for use during and after ACS) are summarized in Table 6 and illustrated
in Figure 9.
ESC Guidelines 3751
Table 6 Dose regimen of antiplatelet and anticoagulant drugs in acute coronary syndrome patients
I. Antiplatelet drugs
Aspirin LD of 150–300 mg orally or 75–250 mg i.v. if oral ingestion is not possible, followed by oral MD of 75–100 mg o.d.; no specific dose adjustment in
CKD patients.
P2Y12 receptor inhibitors (oral or i.v.)
Clopidogrel LD of 300–600 mg orally, followed by an MD of 75 mg o.d.; no specific dose adjustment in CKD patients.
Fibrinolysis: at the time of fibrinolysis an initial dose of 300 mg (75 mg for patients older than 75 years of age).
Prasugrel LD of 60 mg orally, followed by an MD of 10 mg o.d. In patients with body weight <60 kg, an MD of 5 mg o.d. is recommended. In patients aged
≥75 years, prasugrel should be used with caution, but a MD of 5 mg o.d. should be used if treatment is deemed necessary. No specific dose
adjustment in CKD patients. Prior stroke is a contraindication for prasugrel.

Ticagrelor LD of 180 mg orally, followed by an MD of 90 mg b.i.d.; no specific dose adjustment in CKD patients.
Cangrelor Bolus of 30 mcg/kg i.v. followed by 4 mcg/kg/min infusion for at least 2 h or the duration of the procedure (whichever is longer).
In the transition from cangrelor to a thienopyridine, the thienopyridine should be administered immediately after discontinuation of cangrelor
with an LD (clopidogrel 600 mg or prasugrel 60 mg); to avoid a potential DDI, prasugrel may also be administered 30 min before the cangrelor
infusion is stopped. Ticagrelor (LD 180 mg) should be administered at the time of PCI to minimize the potential gap in platelet inhibition during
the transition phase.
GP IIb/IIIa receptor inhibitors (i.v.)
Eptifibatide Double bolus of 180 mcg/kg i.v. (given at a 10-min interval) followed by an infusion of 2.0 mcg/kg/min for up to 18 h.
For CrCl 30–50 mL/min: first LD, 180 mcg/kg i.v. bolus (max 22.6 mg); maintenance infusion, 1 mcg/kg/min (max 7.5 mg/h). Second LD (if PCI),
180 mcg/kg i.v. bolus (max 22.6 mg) should be administered 10 min after the first bolus. Contraindicated in patients with end-stage renal disease
and with prior ICH, ischaemic stroke within 30 days, fibrinolysis, or platelet count <100 000/mm3.
Tirofiban Bolus of 25 mcg/kg i.v. over 3 min, followed by an infusion of 0.15 mcg/kg/min for up to 18 h.
For CrCl ≤60 mL/min: LD, 25 mcg/kg i.v. over 5 min followed by a maintenance infusion of 0.075 mcg/kg/min continued for up to 18 h.
Contraindicated in patients with prior ICH, ischaemic stroke within 30 days, fibrinolysis, or platelet count <100 000/mm3.
II. Anticoagulant drugs
UFH Initial treatment: i.v. bolus 70–100 U/kg followed by i.v. infusion titrated to achieve an aPTT of 60–80 s.
During PCI: 70–100 U/kg i.v. bolus or according to ACT in case of UFH pre-treatment.
Enoxaparin Initial treatment: for treatment of ACS 1 mg/kg b.i.d. subcutaneously for a minimum of 2 days and continued until clinical stabilization. In patients
whose CrCl is below 30 mL per minute (by Cockcroft–Gault equation), the enoxaparin dosage should be reduced to 1 mg per kg o.d.
During PCI: for patients managed with PCI, if the last dose of enoxaparin was given less than 8 h before balloon inflation, no additional dosing is
needed. If the last s.c. administration was given more than 8 h before balloon inflation, an i.v. bolus of 0.3 mg/kg enoxaparin sodium should be
administered.
Bivalirudin During PPCI: 0.75 mg/kg i.v. bolus followed by i.v. infusion of 1.75 mg/kg/h for 4 h after the procedure.
In patients whose CrCl is below 30 mL/min (by Cockcroft–Gault equation), maintenance infusion should be reduced to 1 mg/kg/h.
© ESC 2023
Fondaparinux Initial treatment: 2.5 mg/d subcutaneously.
During PCI: A single bolus of UFH is recommended.
Avoid if CrCl <20 mL/min.
ACS, acute coronary syndrome; ACT, activated clotting time; aPPT, activated partial thromboplastin time; b.i.d., bis in die (twice a day); CKD, chronic kidney disease; CrCl, creatinine
clearance; DDI, drug–drug interactions; ICH, intracranial haemorrhage; i.v. intravenous; LD, loading dose; MD, maintenance dose; o.d., once a day; PPCI, primary percutaneous coronary
intervention; s.c. subcutaneous; UFH, unfractionated heparin.
3752 ESC Guidelines
Plaque rupture or
plaque erosion ADP
Eptifibatide
Tirofiban
P P
Platelet GP IIb/IIIa

activation
P2Y12 receptor
TF:FVIIa Aggregation of
activated platelets
Thrombin
Rivaroxaban receptor
Apixaban Clopidogrel
Edoxaban Thromboxane Ticagrelor
receptor
Prasugrel
Fondaparinux FXa Cangrelor
UFH Aspirin
Enoxaparin
TxA2
Dabigatran
Thrombin Fibrin
Bivalirudin Fibrinogen Mature
fibrin clot
Figure 9 Antithrombotic treatments in acute coronary syndrome: pharmacological targets. ADP, adenosine diphosphate; FVIIa, Factor VIIa; FXa, Factor Xa;
GP, glycoprotein; TF, tissue factor; TxA2, thromboxane A2; UFH, unfractionated heparin. Drugs with oral administration are shown in blue and drugs with
preferred parenteral administration in red.
6.1. Antiplatelet therapy in the acute presence of one major or two minor ARC-HBR risk factors indicates
high bleeding risk (HBR). Of note, the presence of multiple major risk
phase factors is associated with a progressive increase in the bleeding risk.234
6.1.1. Oral antiplatelet therapy Aspirin treatment is started with a loading dose (LD) as soon as pos-
Antiplatelet drugs play a key role in the acute phase of treatment for sible, followed by maintenance treatment (Table 6).235 Current evi-
ACS. Table 6 summarizes the dosing regimens of the available oral dence supports an aspirin maintenance dose (MD) of 75–100 mg
and i.v. antiplatelet drugs. The choice of antiplatelet regimen should once a day (o.d.).236,237
take the bleeding risk of the patient into account. Factors associated Based on the results of the phase III PLATelet inhibition and patient
with an elevated bleeding risk have been detailed by the Academic Outcomes (PLATO) and TRial to Assess Improvement in Therapeutic
Research Consortium on High Bleeding Risk (ARC-HBR).233 The Outcomes by Optimizing Platelet InhibitioN with Prasugrel
ESC Guidelines 3753
Thrombolysis In Myocardial Infarction 38 (TRITON-TIMI 38) studies, 6.1.2.2. Pre-treatment in patients with non-ST-elevation acute
dual antiplatelet therapy (DAPT) including aspirin and a potent P2Y12 coronary syndrome
receptor inhibitor (prasugrel or ticagrelor) is recommended as the de- The randomized A Comparison of Prasugrel at the Time of
fault DAPT strategy for ACS patients.238,239 Clopidogrel, which is char- Percutaneous Coronary Intervention or as Pretreatment at the Time
acterized by less effective and more variable platelet inhibition, should of Diagnosis in Patients with Non-ST Elevation Myocardial Infarction
only be used when prasugrel or ticagrelor are contraindicated/not avail- (ACCOAST) trial not only demonstrated a lack of benefit with respect
able, or in some patients considered otherwise at HBR (e.g. ≥1 major to ischaemic outcomes with prasugrel pre-treatment, but also a sub-
or ≥2 minor ARC-HBR criteria).233,240–242 In addition, the use of clopi- stantially higher bleeding risk.247 In this study, the median time from first
dogrel may be considered in older patients (e.g. ≥70 years).242,243 LD to the start of coronary angiography in the pre-treatment group
Prasugrel should be considered in preference to ticagrelor for ACS was 4.4 h. With respect to pre-treatment data for ticagrelor, the
patients who proceed to PCI. The Intracoronary Stenting and ISAR-REACT 5 trial showed that a ticagrelor-based strategy with rou-
Antithrombotic Regimen Rapid Early Action for Coronary Treatment tine pre-treatment was inferior to a prasugrel-based strategy with a de-
(ISAR-REACT) 5 RCT is the largest head-to-head comparison of 1-year

ferred LD in NSTE-ACS patients.244 The DUBIUS (Downstream
DAPT with prasugrel vs. DAPT with ticagrelor in patients with ACS Versus Upstream Strategy for the Administration of P2Y12 Receptor
planned for invasive evaluation, >80% of whom underwent PCI.244 A Blockers) trial also attempted to address this question but was stopped
treatment strategy with prasugrel (LD given as soon as possible after ran- early for futility as there was no difference between upstream vs. down-
domization for patients undergoing PPCI and after delineation of coron- stream oral P2Y12 administration in patients with NSTE-ACS (both
ary anatomy for patients presenting with NSTE-ACS) vs. ticagrelor (LD NSTEMI and UA) scheduled for coronary angiography within 72 h of
given as soon as possible after randomization in all cases) significantly re- hospital admission.248
duced the composite endpoint of death, MI, or stroke (6.9% vs. 9.3%, P =
0.006) without any increase in bleeding complications (4.8% vs. 5.4%, P =
6.1.2.3. Summary of pre-treatment strategies
0.46). Limitations of this study include an open-label design and limited
data on medically managed or CABG-treated patients. In patients with a working diagnosis of STEMI undergoing PPCI, pre-
treatment with a P2Y12 receptor inhibitor may be considered.245 In pa-
tients with a working diagnosis of NSTE-ACS, routine pre-treatment
6.1.2. Timing of loading dose of oral antiplatelet with a P2Y12 receptor inhibitor before knowing the coronary anatomy
therapy in patients anticipated to undergo an early invasive strategy (i.e. <24 h)
Both aspirin and oral P2Y12 inhibitors achieve platelet inhibition more is not recommended.244,245,247 For patients with a working diagnosis of
rapidly following an oral LD. Pre-treatment refers to a strategy in which NSTE-ACS, where there is an anticipated delay to invasive angiography
an antiplatelet drug, usually a P2Y12 receptor inhibitor, is given before (i.e. >24 h), pre-treatment with a P2Y12 receptor inhibitor may be con-
coronary angiography and, therefore, before the coronary anatomy is sidered according to the bleeding risk of the patient. In all ACS patients
known. Although a potential benefit with pre-treatment in the setting proceeding to PCI who did not receive P2Y12 receptor inhibitor pre-
of ACS has been hypothesized, large-scale randomized trials supporting treatment, an LD is recommended at the time of PCI.
a routine pre-treatment strategy with P2Y12 receptor inhibitors are
lacking. Caution in relation to pre-treatment may be of particular rele- 6.1.3. Intravenous antiplatelet drugs
vance in patients at HBR (e.g. those receiving an oral anticoagulant Peri-interventional i.v. antiplatelet drugs include P2Y12 receptor inhibi-
[OAC]). tors (cangrelor) and glycoprotein (GP) IIb/IIIa inhibitors (eptifibatide
and tirofiban). Most of the trials evaluating GP IIb/IIIa inhibitors in
PCI-treated ACS patients pre-date the era of routine DAPT, in particu-
6.1.2.1. Pre-treatment in patients with suspected ST-elevation lar, early initiation of DAPT including an LD of a potent P2Y12 receptor
myocardial infarction inhibitor.249,250 There is no strong evidence for any additional benefit
The Administration of Ticagrelor in the Cath Lab or in the Ambulance with the routine use of GP IIb/IIIa inhibitors in ACS patients scheduled
for New ST Elevation Myocardial Infarction to Open the Coronary for coronary angiography. Nevertheless, their use should be considered
Artery (ATLANTIC) trial is the only randomized study testing the for bailout if there is evidence of no-reflow or a thrombotic complica-
safety and efficacy of different timings of P2Y12 receptor inhibitor initi- tion during PCI. Another potential use for GP IIb/IIIa inhibitors is in the
ation in patients with a working diagnosis of STEMI undergoing PPCI.245 setting of high-risk PCI in patients who have not been pre-treated with
In this trial, patients were randomized to receive a ticagrelor LD either P2Y12 receptor inhibitors.
during transfer to a PPCI centre or immediately before angiography.245 Cangrelor is a direct reversible, short-acting P2Y12 receptor inhibitor
The median difference between the timing of P2Y12 receptor inhibitor that has been evaluated during PCI for CCS and ACS in clinical trials
loading with the two treatment strategies was 31 min. In this study, the against clopidogrel, both with administration before (Cangrelor versus
pre-treatment strategy failed to meet the pre-specified primary end- Standard Therapy to Achieve Optimal Management of Platelet
point of improved ST-segment elevation resolution or Thrombolysis Inhibition [CHAMPION PCI]) and after (CHAMPION PLATFORM
In Myocardial Infarction (TIMI) flow before intervention. Rates of major and CHAMPION PHOENIX [A Clinical Trial Comparing Cangrelor
and minor bleeding events were identical in both treatment arms. to Clopidogrel Standard Therapy in Subjects Who Require
These results were supported by real-world data obtained from the Percutaneous Coronary Intervention]) PCI.251–253 A meta-analysis of
SWEDEHEART (Swedish Web-System for Enhancement and these trials showed that the benefit of cangrelor with respect to major
Development of Evidence-Based Care in Heart Disease Evaluated ischaemic endpoints was counterbalanced by an increase in minor
According to Recommended Therapies) registry in STEMI patients.246 bleeding complications.254 It is also important to note that the benefit
Prasugrel pre-treatment has not been directly investigated in patients of cangrelor with respect to ischaemic endpoints was attenuated in
with STEMI. CHAMPION PCI with upfront administration of clopidogrel, and
3754 ESC Guidelines
data for its use in conjunction with ticagrelor or prasugrel treatment are bivalirudin group.259 Based on the totality of the available data, bivalir-
limited. Due to its proven efficacy in preventing intra-procedural and udin with a full-dose post-PCI infusion should be considered as an alter-
post-procedural stent thrombosis in P2Y12 receptor inhibitor-naïve pa- native to UFH, although further studies to confirm these findings in
tients, cangrelor may be considered on a case-by-case basis in P2Y12 re- non-East Asian populations are required. Bivalirudin is also the recom-
ceptor inhibitor-naïve ACS patients undergoing PCI, including in mended alternative to UFH in patients presenting with ACS who have a
patients for whom it may not be feasible to give oral drugs in the setting history of heparin-induced thrombocytopaenia. Additional information
of emergent PCI (e.g. CS patients and/or patients on mechanical about bivalirudin, including evidence tables summarizing the relevant
ventilation). clinical trials, is provided in the Supplementary data online.
Based on the results of the OASIS-6 (The Safety and Efficacy of
6.2. Anticoagulant treatment in the acute Fondaparinux Versus Control Therapy in Patients With ST Segment
Elevation Acute Myocardial Infarction) trial, fondaparinux is not recom-
phase mended in patients with STEMI undergoing PPCI.260
Anticoagulation is an important component of the initial treatment of
To summarize, parenteral anticoagulation is recommended for pa-

ACS and of the peri-procedural treatment for ACS patients managed
tients with STEMI undergoing PPCI and UFH is the default choice of
with an invasive strategy. Therefore, parenteral anticoagulation is re-
anticoagulant at present. Enoxaparin and bivalirudin should be consid-
commended for all ACS patients at the time of diagnosis.255 Table 6
ered as alternatives to UFH in these patients but fondaparinux is not
provides an overview of the relevant anticoagulant drugs and their dos-
recommended.
ing in ACS patients.
In general, a crossover between anticoagulants should be avoided in
patients with ACS (especially between unfractionated heparin [UFH] 6.2.2. Anticoagulation in patients with
and low-molecular-weight heparin [LMWH]), with the exception of non-ST-elevation acute coronary syndrome
adding UFH to fondaparinux when a patient presenting with undergoing angiography and percutaneous coronary
NSTE-ACS proceeds to PCI after a period of fondaparinux treatment intervention if indicated
(see below for further detail).256,257 Anticoagulants should generally be
Patients with NSTE-ACS are also recommended to receive parenteral
discontinued immediately after PCI, except in specific clinical settings
anticoagulation. In patients with NSTE-ACS who are anticipated to
such as the confirmed presence of LV aneurysm with thrombus forma-
undergo immediate or early (i.e. <24 h from the time of diagnosis) in-
tion or AF requiring anticoagulation. In addition, for bivalirudin in pa-
vasive angiography and PCI if indicated, parenteral anticoagulation at
tients with STEMI undergoing PCI, a full dose post-PCI infusion is
the time of diagnosis is recommended, and UFH has been historically
recommended.
established as the anticoagulant of choice. However, in a meta-analysis
In this section of the guideline, we summarize the recommendations
of trials comparing UFH with enoxaparin, mortality and major bleeding
for anticoagulant treatment in the acute phase for patients with STEMI
was not different between both agents in patients with NSTE-ACS or
undergoing PPCI and for patients with NSTE-ACS undergoing angiog-
stable patients scheduled for PCI.261 Therefore, enoxaparin should be
raphy (and PCI if indicated).
considered as an alternative to UFH in these patients (especially in cases
where monitoring of clotting times is complex).
6.2.1. Anticoagulation in patients with ST-elevation NSTE-ACS patients who do not undergo early invasive angiography
myocardial infarction undergoing primary (i.e. within 24 h of diagnosis) will have an extended initial treatment
percutaneous coronary intervention phase consisting of only pharmacological treatment. In these patients,
Unfractionated heparin has been established as the standard of care in fondaparinux therapy is recommended in preference to enoxaparin
patients with STEMI undergoing PPCI due to its favourable risk/benefit while awaiting invasive angiography, based on the favourable outcomes
profile. In these patients, anticoagulation should be given during the in- demonstrated with fondaparinux in comparison to enoxaparin in the
vasive procedure. High-quality evidence with respect to the benefit of Fifth Organization to Assess Strategies in Acute Ischemic Syndromes
administering anticoagulation at an earlier time point in patients under- (OASIS-5) trial.262 Of note, guiding catheter thrombus formation was
going a PPCI strategy is lacking. of concern with fondaparinux and, therefore, a full-dose bolus of
Alternatives to UFH that should be considered in patients with UFH should be given if the patient proceeds to PCI. The potential im-
STEMI undergoing PPCI include enoxaparin (a LMWH) and bivalirudin pact of contemporary changes in clinical practice (including radial ac-
(a direct thrombin inhibitor). The ATOLL (STEMI Treated With cess, early catheterization, and infrequent GP IIb/IIIa inhibitor
Primary Angioplasty and Intravenous Lovenox or Unfractionated therapy) on the treatment effect observed in OASIS-5 should also be
Heparin) trial reported a reduction in the primary endpoint at 30 considered. If fondaparinux is not available, enoxaparin should be con-
days (incidence of death, complication of MI, procedure failure, or ma- sidered for these patients.
jor bleeding) with enoxaparin in comparison to UFH in patients with Intravenous enoxaparin should also be considered as an anticoagu-
STEMI undergoing PPCI.258 lant for PCI in patients with NSTE-ACS in whom subcutaneous (s.c.)
In the BivaliRudin with prolonged full-dose Infusion durinG primary enoxaparin was used while awaiting coronary angiography.261
PCI versus Heparin Trial 4 (BRIGHT-4), 6016 patients with STEMI In summary, parenteral anticoagulation is recommended for patients
undergoing PPCI were randomized to either bivalirudin (with a full with NSTE-ACS. For patients with NSTE-ACS undergoing immediate
dose post-PCI infusion) or UFH.259 The use of GP IIb/IIIa inhibitors or early angiography (± PCI if indicated), UFH is recommended but en-
was restricted to patients who experienced thrombotic complications. oxaparin should be considered as an alternative to UFH. For patients
The primary endpoint (a composite of all-cause mortality or Bleeding with NSTE-ACS who are not anticipated to undergo early angiography,
Academic Research Consortium [BARC] type 3–5 bleeding at 30 fondaparinux (with a UFH bolus at time of PCI) is recommended in
days), the individual components of the primary endpoint, and definite preference to enoxaparin, although enoxaparin should be considered
or probable stent thrombosis were all significantly reduced in the if fondaparinux is not available.
ESC Guidelines 3755
6.3. Maintenance antithrombotic therapy generally recommended for 12 months, irrespective of the stent
type, unless there are contraindications.236,238,239,244,263 In specific clin-
after revascularization ical scenarios, the default DAPT duration can be shortened (<12
While continuation of anticoagulation after PCI is not necessary in the
months), extended (>12 months), or modified (switching DAPT,
vast majority of patients (i.e. those without an indication for long-term
DAPT de-escalation). The recommended default antithrombotic treat-
OAC), post-interventional antiplatelet treatment is mandatory in ACS
ment options for ACS patients without an indication for OAC are
patients. Following PCI, a default DAPT regimen consisting of a potent
shown in Figure 10.
P2Y12 receptor inhibitor (prasugrel or ticagrelor) and aspirin is
STEMI NSTE-ACS

PPCI PPCI PPCI PPCI Angiography Angiography Angiography
<24 h <24 h >24 h
Anticoagulation UFH Enoxaparin Bivalirudin Fondaparinux UFH Enoxaparin Fondaparinuxa
(Class I) (Class IIa) (Class IIa) (Class III) (Class I) (Class IIa) (Class I)
ACS PPCI NSTE-ACSb

Routine Aspirin P2Y12 inhibitor P2Y12 inhibitor
antiplatelet
(Class I) (Class IIb) (Class III)
pretreatment
Invasive Coronary Angiography
ACS
Prasugrel
Proceeding to PCI
Ticagrelor
Choice of If prasugrel and ticagrelor Prasugrel > Ticagrelor
P2Y12 inhibitorc are unavailable, contraindicated,
or cannot be tolerated (Class IIa)
Clopidogrel
(Class I)
Aspirin
1
+
3
Default DAPT P2Y12 inhibitor
Time
strategy for the 6
(months)
first 12 months (Class I)
after ACSc 9
12
Aspirin
Default strategy
beyond the first (Class I)
12 months
after ACS
Figure 10 Recommended default antithrombotic therapy regimens in acute coronary syndrome patients without an indication for oral anticoagulation.
ACS, acute coronary syndrome; DAPT, dual antiplatelet therapy; HBR, high bleeding risk; NSTE-ACS, non-ST-elevation acute coronary syndrome; PCI, per-
cutaneous coronary intervention; PPCI, primary percutaneous coronary intervention; UFH, unfractionated heparin. Algorithm for antithrombotic therapy in
ACS patients without an indication for oral anticoagulation undergoing invasive evaluation. aFondaparinux (plus a single bolus of UFH at the time of PCI) is
recommended in preference to enoxaparin for NSTE-ACS patients in cases of medical treatment or logistical constraints for transferring the NSTE-ACS
patient to PCI within 24 h of symptom onset. bRoutine pre-treatment with a P2Y12 receptor inhibitor in NSTE-ACS patients in whom coronary anatomy
is not known and early invasive management (<24 h) is planned is not recommended, but pre-treatment with a P2Y12 receptor inhibitor may be considered in
NSTE-ACS patients who are not expected to undergo an early invasive strategy (<24 h) and do not have HBR. cClopidogrel is recommended for 12 months
DAPT if prasugrel and ticagrelor are not available, cannot be tolerated, or are contraindicated, and may be considered in older ACS patients (typically defined
as older than 70–80 years of age).
3756 ESC Guidelines
6.3.1. Shortening dual antiplatelet therapy adverse cardiac or cerebral events were comparable between the
Several RCTs and meta-analyses have compared standard 12-month groups, whereas major or clinically relevant non-major bleeding events
DAPT with ≤6 months DAPT followed by aspirin monotherapy in were significantly reduced in the abbreviated therapy group.
ACS patients.264–267 In some of these trials, the reduction in bleeding
events associated with abbreviated DAPT regimens came at the cost
of an increase in the rates of ischaemic complications. In a large-scale 6.3.2. De-escalation from potent P2Y12 inhibitor to
network meta-analysis, 3-month DAPT but not 6-month DAPT was as- clopidogrel
sociated with higher rates of MI or stent thrombosis in ACS patients.264 The need to switch between oral P2Y12 receptor inhibitors is not
A number of large RCTs have investigated DAPT duration further uncommon as a consequence of bleeding complications (or concern re-
shortened to 1–3 months followed by P2Y12 receptor inhibitor mono- garding bleeding), non-bleeding side effects (e.g. dyspnoea on ticagrelor,
therapy in patients with and without ACS.268–271 In general, low to allergic reactions), and socioeconomic factors.277,278 As such, switching
intermediate ischaemic risk patients were included, and early mono- between oral P2Y12 receptor inhibitors may be considered in selected

therapy with clopidogrel or ticagrelor was used. Some trials included cases.
a comparison with more prolonged DAPT than usual in the control P2Y12 receptor inhibitor de-escalation (i.e. switching from prasugrel/
arm. Patients with STEMI tended to be excluded or under-represented. ticagrelor to clopidogrel) in ACS patients may be considered as an al-
The TWILIGHT (Ticagrelor With Aspirin or Alone in High-Risk ternative strategy to the default treatment regimen in order to reduce
Patients After Coronary Intervention) trial examined the effect of tica- the risk of bleeding events. However, it is important to note that there
grelor monotherapy vs. ticagrelor plus aspirin for 1 year after 3 months is a potential risk of increased ischaemic events with de-escalation and
of DAPT (ticagrelor and aspirin) on clinically relevant bleeding. This this strategy is not recommended in the first 30 days after the index
study enrolled ‘high-risk’ patients as per the trial inclusion criteria, ACS event. In the TROPICAL-ACS (Testing Responsiveness to
which meant that the enrolled patients had at least one clinical feature Platelet Inhibition on Chronic Antiplatelet Treatment For Acute
and one angiographic feature associated with a high risk of ischaemic or Coronary Syndromes) trial (44% NSTE-ACS, 56% STEMI), an approach
bleeding events. However, in order to be randomized the patients were of DAPT de-escalation from prasugrel to clopidogrel (at 2 weeks after
also required to have not experienced a major bleeding or ischaemic ACS) was guided by platelet function testing and was non-inferior to
event in the 3 months following hospital discharge.271 STEMI patients standard treatment with prasugrel at 1 year after PCI in terms of net
were excluded from this study. Bleeding events (BARC type 2, 3, or clinical benefit.279 In the Cost-effectiveness of CYP2C19 Genotype
5 bleeding) were significantly reduced by omitting aspirin after 3 Guided Treatment With Antiplatelet Drugs in Patients With
months, without a signal of increased ischaemic risk. A dedicated sub- ST-segment-elevation Myocardial Infarction Undergoing Immediate
group analysis suggested these findings were consistent in 4614 patients PCI With Stent Implantation: Optimization of Treatment (POPular
with NSTEMI/UA.272 In the TICO (Ticagrelor Monotherapy After 3 Genetics) trial, DAPT de-escalation from ticagrelor/prasugrel to clopi-
Months in the Patients Treated With New Generation Sirolimus dogrel guided by CYP2C19 genotyping in ACS patients undergoing
Stent for Acute Coronary Syndrome) trial, ticagrelor monotherapy PPCI within the previous 48 h was non-inferior to standard treatment
vs. ticagrelor plus aspirin for up to 1 year after 3 months of DAPT (ti- with ticagrelor or prasugrel at 12 months with respect to thrombotic
cagrelor and aspirin) was tested in 3056 ACS patients (36% STEMI).273 events and resulted in a lower incidence of bleeding.280
Net adverse clinical events and major bleeding events were significantly The single-centre TOPIC (Timing of Platelet Inhibition After Acute
reduced with ticagrelor monotherapy, and major adverse cardiac and Coronary Syndrome) trial used an unguided de-escalation approach in
cerebrovascular events were not significantly different. Limitations of 645 ACS patients (60% NSTE-ACS, 40% STEMI) from ticagrelor/prasu-
this study included the selected population assessed and the lower grel to clopidogrel after 1 month of DAPT with ticagrelor/prasugrel
than expected event rates. A study-level meta-analysis of outcomes and aspirin. Net adverse clinical events and bleeding events were reduced,
in a population of patients (with both ACS and CCS) fitted with a whereas the rate of ischaemic endpoints was unchanged.281 The
DES also reported a beneficial effect of shortened DAPT for 1–3 TALOS-AMI (TicAgrelor versus CLOpidogrel in Stabilised Patients with
months on major bleeding events, as well as a neutral effect on death, Acute Myocardial Infarction) trial investigated unguided de-escalation in
MI, and stroke.274 2697 ACS patients (46% NSTEMI/UA, 54% STEMI) from ticagrelor to clo-
The STOPDAPT-2-ACS (ShorT and OPtimal Duration of Dual pidogrel after 1 month of DAPT with ticagrelor and aspirin.282 This uni-
AntiPlatelet Therapy-2 Study for the Patients With ACS) trial investi- form unguided de-escalation strategy led to significant 12-month
gated a short DAPT strategy in ACS patients.275 At 1–2 months, pa- reductions in net adverse clinical events and bleeding events. The
tients were randomized to either clopidogrel monotherapy or HOST-REDUCE-POLYTECH-ACS (Harmonizing Optimal Strategy for
continued DAPT for 12 months. Non-inferiority of the investigational Treatment of Coronary Artery Diseases Trial—Comparison of
strategy for the composite endpoint of cardiovascular (CV) or bleeding REDUCTION of PrasugrEl Dose & POLYmer TECHnology in ACS
events was not proven, suggesting that systematic very short duration Patients) trial tested a different method of de-escalation—a reduction
DAPT (i.e. <3 months) followed by clopidogrel monotherapy is not a in prasugrel dose rather than switching to clopidogrel. In this trial, 2338
useful strategy in ACS patients. low-risk ACS patients <75 years of age (14% STEMI, 25% NSTEMI, and
The MASTER DAPT (Management of High Bleeding Risk Patients Post 61% UA) were randomized to low-dose prasugrel (5 mg daily) or
Bioresorbable Polymer Coated Stent Implantation With an Abbreviated standard-dose prasugrel (10 mg daily) after 1 month of DAPT with
Versus Prolonged DAPT Regimen) trial examined a strategy of abbre- standard-dose prasugrel.283 Prasugrel dose de-escalation was associated
viated DAPT (1 month) followed by either aspirin or P2Y12 inhibitor with fewer net adverse clinical events and bleeding events, mainly by re-
monotherapy vs. DAPT ≥3 months (standard therapy) in a cohort of ducing bleeding events without an increase in ischaemic events. It should
4579 HBR patients (49% ACS, 12% STEMI) undergoing PCI with a bioab- be noted that the TALOS-AMI and HOST-REDUCE-POLYTECH-ACS
sorbable polymer-coated stent.276 Net adverse clinical events and major trials only included East Asian populations.
ESC Guidelines 3757
6.3.3. Summary of alternative antiplatelet strategies 12 months DAPT. From a practical perspective, this means that these
to reduce bleeding risk in the first 12 months after strategies should not be employed as a default strategy in the wider
acute coronary syndrome ACS population but can be considered when there is a specific motiv-
Considering the totality of evidence from the scientific literature, alterna- ation for their use (i.e. aiming to reduce the risk of bleeding events in
tives to the default strategy of 12 months DAPT in patients with ACS in- HBR patients or if there are other specific concerns regarding a
clude shortening the DAPT duration to 1 or 3–6 months (depending on 12-month potent P2Y12 inhibitor-based DAPT regimen).
the balance of bleeding and ischaemic risks) and de-escalating DAPT from De-escalation of antiplatelet therapy in the first 30 days is not recom-
prasugrel/ticagrelor-based DAPT to clopidogrel-based DAPT. However, mended, but de-escalation of P2Y12 receptor inhibitor therapy may be
it should be noted that much of the evidence on these strategies in ACS considered as an alternative strategy beyond 30 days after an ACS, in
patients is derived from trials powered primarily for bleeding outcomes, order to reduce the risk of bleeding events. DAPT abbreviation strat-
many of which had a non-inferiority design and were, therefore, not pow- egies (followed preferably by P2Y12 inhibitor monotherapy within the
ered to detect potentially relevant differences in ischaemic outcomes. The first 12 months post-ACS) should be considered in patients who are
event-free after 3–6 months of DAPT and who are not high ischaemic

patient populations enrolled in these studies were also often relatively se-
lected, often excluding or under-representing the highest risk ACS pa- risk, with the duration of DAPT guided by the ischaemic and bleeding
tients. As such, it is important to reflect that even meta-analyses of the risks of the patient. For HBR patients, aspirin or P2Y12 receptor inhibi-
available randomized evidence cannot overcome the potential selection tor monotherapy after 1 month of DAPT may be considered. Please
bias at the point of entry in the relevant randomized trials. see Recommendation Table 6 for full details. These alternative antipla-
These important limitations explain why these strategies should at telet strategies to reduce bleeding risk in the first 12 months after ACS
present remain considered as alternative strategies to the default of are also summarized in Figure 11.
Antiplatelet strategies to reduce bleeding risk in the first 12 months after ACS
Abbreviated DAPT strategies DAPT de-escalation strategies
In HBR
In HBR and
patients Potent P2Y12 inhibitor-based DAPT
non-HBR patients
only
0
1 month Aspirin + Prasugrel OR Aspirin + Ticagrelor
DAPT
1
3 month
DAPT De-escalation
6 month Change from potent P2Y12

3 DAPT inhibitor to clopidogrel
Aspirin + Clopidogrel
Time
(Months) 6
P2Y12 inhibitor
or
aspirin monotherapy
12
Figure 11 Alternative antiplatelet strategies to reduce bleeding risk in the first 12 months after an ACS. ACS, acute coronary syndrome; DAPT, dual
antiplatelet therapy; HBR, high bleeding risk; PFT, platelet function test.
3758 ESC Guidelines
To summarise, antiplatelet strategies to reduce bleeding risk in the first Pre-treatment with a P2Y12 receptor inhibitor may
12 months after an ACS can be divided into abbreviated DAPT strategies be considered in patients undergoing a primary PCI IIb B
and DAPT de-escalation strategies. Twelve-month DAPT (preferably strategy.244,245
with prasugrel or ticagrelor) remains the default strategy for patients Pre-treatment with a P2Y12 receptor inhibitor may
with ACS (Figure 10) and these strategies should only be used as alterna- be considered in NSTE-ACS patients who are not
tives to this strategy, in general driven by a motivation to reduce the risk IIb C
expected to undergo an early invasive strategy
of bleeding events (i.e. if the patient is HBR or if there are other specific
(<24 h) and do not have HBRc.263
concerns regarding 12-month potent P2Y12 inhibitor-based DAPT).
Pre-treatment with a GP IIb/IIIa receptor antagonist
The specific alternative antiplatelet strategies employed (i.e. choice III A
is not recommended.292
of P2Y12 inhibitor, duration of DAPT, choice of SAPT agent) to reduce
bleeding risk should be chosen based on the bleeding risk of the patient Routine pre-treatment with a P2Y12 receptor
(HBR or not) and these recommendations are summarized in inhibitor in NSTE-ACS patients in whom coronary
Recommendation Table 6. anatomy is not known and early invasive III A

management (<24 h) is planned is not
Recommendation Table 5 — Recommendations for recommended.244,247,248,293–295
antiplatelet and anticoagulant therapy in acute coronary Anticoagulant therapy
syndrome
Parenteral anticoagulation is recommended for all
I A
Recommendations Classa Levelb patients with ACS at the time of diagnosis.255,296
Routine use of a UFH bolus (weight-adjusted i.v.
Antiplatelet therapy bolus during PCI of 70–100 IU/kg) is recommended I C
Aspirin is recommended for all patients without in patients undergoing PCI.
contraindications at an initial oral LD of 150–300 mg Intravenous enoxaparin at the time of PCI should be
I A
(or 75–250 mg i.v.) and an MD of 75–100 mg o.d. for considered in patients pre-treated with IIa B
long-term treatment.284,285 subcutaneous enoxaparin.256,261,297
In all ACS patients, a P2Y12 receptor inhibitor is Discontinuation of parenteral anticoagulation should
recommended in addition to aspirin, given as an initial be considered immediately after an invasive IIa C
I A
oral LD followed by an MD for 12 months unless procedure.
there is HBRc.238,239,263,286
Patients with STEMI
A proton pump inhibitor in combination with DAPT
Enoxaparin should be considered as an alternative to
is recommended in patients at high risk of I A IIa A
287,288 UFH in patients with STEMI undergoing PPCI.258,261,298
gastrointestinal bleeding.
Bivalirudin with a full-dose post PCI infusion should
Prasugrel is recommended in P2Y12 receptor
be considered as an alternative to UFH in patients IIa A
inhibitor-naïve patients proceeding to PCI (60 mg
I B with STEMI undergoing PPCI.259,299,300–303
LD, 10 mg o.d. MD, 5 mg o.d. MD for patients aged
Fondaparinux is not recommended in patients with
≥75 years or with a body weight <60 kg).239 III B
STEMI undergoing PPCI.260
Ticagrelor is recommended irrespective of the
treatment strategy (invasive or conservative) I B Patients with NSTE-ACS
(180 mg LD, 90 mg b.i.d. MD).238 For patients with NSTE-ACS in whom early invasive
Clopidogrel (300–600 mg LD, 75 mg o.d. MD) is angiography (i.e. within 24 h) is not anticipated, I B
recommended when prasugrel or ticagrelor are not fondaparinux is recommended.262,304
I C
available, cannot be tolerated, or are For patients with NSTE-ACS in whom early invasive
contraindicated.263,289 angiography (i.e. within 24 h) is anticipated, enoxaparin IIa B
If patients presenting with ACS stop DAPT to should be considered as an alternative to UFH.256
undergo CABG, it is recommended they resume I C Combining antiplatelets and OAC
DAPT after surgery for at least 12 months. As the default strategy for patients with atrial
Prasugrel should be considered in preference to fibrillation and CHA2DS2-VASc score ≥1 in men and
ticagrelor for ACS patients who proceed to IIa B ≥2 in women, after up to 1 week of triple
PCI.244,290 antithrombotic therapy following the ACS event,
I A
GP IIb/IIIa receptor antagonists should be considered dual antithrombotic therapy using a NOAC at the
if there is evidence of no-reflow or a thrombotic IIa C recommended dose for stroke prevention and a
complication during PCI. single oral antiplatelet agent (preferably clopidogrel)
In P2Y12 receptor inhibitor-naïve patients for up to 12 months is recommended.305–310
IIb A
undergoing PCI, cangrelor may be considered.251–254 During PCI, a UFH bolus is recommended in any of
In older ACS patients,d especially if HBR,c clopidogrel the following circumstances:
I C
as the P2Y12 receptor inhibitor may be IIb B • if the patient is on a NOAC
considered.242,243,291 • if the INR is <2.5 in VKA-treated patients.
Continued Continued
ESC Guidelines 3759
In patients with an indication for OAC with VKA in Further information regarding long-term antithrombotic strategies (i.e.
combination with aspirin and/or clopidogrel, careful beyond 12 months) is provided in the Supplementary data online.
regulation of the dose intensity of VKA with a target IIa B
INR of 2.0–2.5 and a time in the therapeutic range 6.4.1. Prolonging antithrombotic therapy beyond 12
>70% should be considered.305–308,311 months
When rivaroxaban is used and concerns about HBR Prolonged antithrombotic therapy options: See
prevail over ischaemic stroke, rivaroxaban 15 mg o.d. Supplementary data online, Figure S4; Tables S7 and S8 for additional in-
should be considered in preference to rivaroxaban IIa B formation.314–319
20 mg o.d. for the duration of concomitant SAPT or
DAPT.307 Recommendation Table 6 — Recommendations for
In patients at HBR,c dabigatran 110 mg b.i.d. should alternative antithrombotic therapy regimens
be considered in preference to dabigatran 150 mg

IIa B
b.i.d. for the duration of concomitant SAPT or Recommendations Classa Levelb
DAPT, to mitigate bleeding risk.305
Shortening/de-escalation of antithrombotic therapy
In patients requiring anticoagulation and treated
In patients who are event-free after 3–6 months of
medically, a single antiplatelet agent in addition to an IIa B
308,312 DAPT and who are not high ischaemic risk, single
OAC should be considered for up to 1 year.
antiplatelet therapy (preferably with a P2Y12 IIa A
In patients treated with an OAC, aspirin plus
receptor inhibitor) should be considered.264,268–
clopidogrel for longer than 1 week and up to 1 271,273,274,276,313,320
month should be considered in those with high
IIa C De-escalation of P2Y12 receptor inhibitor treatment
ischaemic risk or with other anatomical/procedural
(e.g. with a switch from prasugrel/ticagrelor to
characteristics that are judged to outweigh the IIb A
clopidogrel) may be considered as an alternative
bleeding risk.e 279–282,321,322
DAPT strategy to reduce bleeding risk.
In patients requiring OAC, withdrawing antiplatelet
In HBR patients, aspirin or P2Y12 receptor inhibitor
therapy at 6 months while continuing OAC may be IIb B
monotherapy after 1 month of DAPT may be IIb B
considered.313
© ESC 2023
considered.276,313
The use of ticagrelor or prasugrel as part of triple
III C De-escalation of antiplatelet therapy in the first 30
antithrombotic therapy is not recommended. III B
days after an ACS event is not recommended.238,323
ACS, acute coronary syndrome; b.i.d., bis in die (twice a day); CHA2DS2-VASc, Congestive
Prolonging antithrombotic therapy
heart failure, Hypertension, Age ≥75 years, Diabetes mellitus, Stroke or transient ischaemic
attack, Vascular disease; DAPT, dual antiplatelet therapy; GP, glycoprotein; HBR, high Discontinuation of antiplatelet treatment in patients
bleeding risk; INR, international normalized ratio; i.v., intravenous; LD, loading dose; MD,
treated with an OAC is recommended after 12 I B
maintenance dose; NOAC, non-vitamin K antagonist oral anticoagulant; NSTE-ACS,
non-ST-elevation acute coronary syndrome; OAC, oral anticoagulant; PPCI, primary months.324,325
percutaneous coronary intervention; SAPT, single antiplatelet therapy; STEMI, Adding a second antithrombotic agent to aspirin for
ST-elevation myocardial infarction; UFH, unfractionated heparin; VKA, vitamin K
extended long-term secondary prevention should be
antagonist. IIa A
a
Class of recommendation. considered in patients with high ischaemic risk and
b
Level of evidence. without HBR . c 314–318
c
HBR should be assessed in a structured manner, e.g. presence of a single major or two
minor characteristics as defined by ARC-HBR (see section 8.2.2.3 in Supplementary data Adding a second antithrombotic agent to aspirin for
online). extended long-term secondary prevention may be
d
The definition of older patients varies across trials, ranging from 70 to 80 years of age. IIb A
considered in patients with moderate ischaemic risk
Frailty and comorbidities should also be taken in consideration.
e
See Antiplatelet therapy in patients requiring oral anticoagulation Section 6.2 in and without HBRc.314–318
Supplementary data online for more information on high-risk features of stent-driven P2Y12 inhibitor monotherapy may be considered as © ESC 2023
recurrent events.
an alternative to aspirin monotherapy for long-term IIb A
treatment.326,327
ACS, acute coronary syndrome; DAPT, dual antiplatelet therapy; HBR, high bleeding risk;
6.4. Long-term treatment OAC, oral anticoagulant.
a
By default, DAPT consisting of a potent P2Y12 receptor inhibitor in add- b
Level of evidence.
ition to aspirin is recommended for a minimum of 12 months after an c
The evidence supporting this approach (prolonged treatment with a second
ACS event; exceptions include patients for whom surgery is urgently antithrombotic agent) is based on trials in which the duration of prolonged treatment
was as follows: mean of 23 months (COMPASS), mean of 18 months (DAPT trial), and
needed, patients in whom OAC is indicated, and patients in whom the
median of 33 months (PEGASUS-TIMI 54). Therefore, the benefits and risks associated
risk of bleeding is too high for other reasons.238,239,263 After PCI for with continuation of these respective treatments beyond these time points is at present
ACS, ischaemic and bleeding events both markedly decrease over time. unclear.
3760 ESC Guidelines
6.5. Antiplatelet therapy in patients OAC was safe with respect to ischaemic events in patients taking clin-
ically indicated long-term OAC therapy.313
requiring oral anticoagulation In patients with ACS, the indication for OAC should be re-assessed
6.5.1. Acute coronary syndrome patients requiring and treatment continued only if a compelling indication exists (e.g. par-
anticoagulation oxysmal, persistent, or permanent AF with a CHA2DS2-VASc
In 6–8% of patients undergoing PCI, long-term OAC is indicated [Congestive heart failure, Hypertension, Age ≥75 years, Diabetes mel-
and should also be continued during the invasive procedure. litus, Stroke or transient ischaemic attack, Vascular disease] score ≥1 in
Interruption of the long-term OAC and bridging with parenteral antic- men and ≥2 in women; mechanical heart valve; or recent/a history of
oagulants may lead to an increase in thrombo-embolic episodes and recurrent or unprovoked deep vein thrombosis or PE). Although
bleeds.328–330 In patients undergoing PCI, it is unknown whether it is they have been tested in a minority of patients in the major RCTs, in
safer to bridge non-vitamin K antagonist (VKA) OACs (NOACs) with the absence of robust safety and efficacy data, the use of prasugrel or
parenteral anticoagulants or to continue NOACs without additional ticagrelor as part of TAT is not recommended. The intensity of OAC
parenteral anticoagulation. In VKA-treated patients, no parenteral antic- should be carefully monitored, with a target INR of 2.0–2.5 in patients

oagulation is needed if the international normalized ratio (INR) is treated with VKA (with the exception of individuals with a mechanical
>2.5.311,331,332 Strategies to minimize PCI-related complications in pa- prosthetic valve in the mitral position).
tients on OAC are listed in Table 7. Overall, in patients with AF without mechanical prosthetic valves or
Evidence on the management of ACS patients with an indication for moderate to severe mitral stenosis, the evidence supports the use of
long-term OAC undergoing PCI is derived from subgroups of NOACs over VKAs as they reduce bleeding risk. DAT with a NOAC
RCTs.305–309,333 Patients with STEMI (who generally carry a higher at the recommended dose for stroke prevention and SAPT (preferably
atherothrombotic risk) were under-represented (∼10% of the study clopidogrel, which was used in >90% of patients in the major RCTs) is
populations) in the major RCTs.305,307–309 Pivotal trials testing the recommended as the default strategy for up to 12 months after up to 1
benefit of NOACs as part of the antithrombotic regimen in patients week of TAT (with NOAC and DAPT consisting of aspirin and clopido-
with an indication for long-term anticoagulation undergoing PCI are dis- grel) (Figure 12)—the up to 1 week duration of TAT is based on the
cussed in the Supplementary data online. median treatment duration in the investigational arm of the
All of these trials were individually powered to address the safety of AUGUSTUS trial.308 Although none of the available RCTs were de-
the tested strategy with regard to bleeding events, but not to reliably assigned to detect differences in ischaemic events, the numerically higher
sess differences in individual ischaemic endpoints. In a meta-analysis of all risk of stent thrombosis and MI is offset by the lower risk of bleeding,
four NOAC-based RCTs comparing dual antithrombotic therapy (DAT) with a resultant neutral effect on total mortality.310,336–338
with triple antithrombotic therapy (TAT) in AF patients undergoing PCI
(encompassing 10 234 patients), the primary safety endpoint Table 7 Suggested strategies to reduce bleeding risk
(International Society on Thrombosis and Haemostasis major or clinically related to percutaneous coronary intervention
relevant non-major bleeding) was significantly lower with DAT vs. TAT
• Anticoagulant doses adjusted to body weight and renal function,
(relative risk [RR] 0.66, 95% CI, 0.56–0.78; P <0.001).310 There were
especially in women and older patients
no significant differences in all-cause and CV death, stroke, or trial-
defined major adverse cardiovascular events (MACE). However, DAT • Radial artery approach as default vascular access
was associated with a borderline increased risk of MI (RR 1.22, 95% • Proton pump inhibitors in patients on dual antiplatelet therapy at
CI, 0.99–1.52; P = 0.07) and a significant increase in stent thrombosis higher-than-average risk of gastrointestinal bleeds (i.e. history of
(RR 1.59, 95% CI, 1.01–2.50; P = 0.04). This translates into an absolute gastrointestinal ulcer/haemorrhage, anticoagulant therapy, chronic
reduction in major bleeding events of 2.3% compared with an absolute non-steroidal anti-inflammatory drug/corticosteroid use), or two or
increase in stent thrombosis of 0.4%, without an effect on overall more of:
MACE. When interpreting the results of these studies, an important gen- (a) Age ≥65 years
eral point is that the treatment effect is confounded by the use of
(b) Dyspepsia
NOACs in the DAT treatment arms and VKAs in the TAT arms.
(c) Gastro-oesophageal reflux disease
Secondary analyses from the AUGUSTUS (An Open-Label, 2 × 2
(d) Helicobacter pylori infection
Factorial, Randomized Controlled, Clinical Trial to Evaluate the Safety
(e) Chronic alcohol use
of Apixaban Versus Vitamin K Antagonist and Aspirin Versus Aspirin
Placebo in Patients With Atrial Fibrillation and Acute Coronary • In patients on OAC:
Syndrome or Percutaneous Coronary Intervention) trial indicate that (a) PCI performed without interruption of VKAs or NOACs
the stent thrombosis rate was highest within the first 30 days after ran- (b) In patients on VKAs, do not administer UFH if INR >2.5
domization, with higher rates in the non-aspirin group.334 Aspirin treat- (c) In patients on NOACs, regardless of the timing of the last
ment reduced ischaemic events (CV death, MI, stroke, stent administration of NOACs, add low-dose parenteral
thrombosis) but also increased major bleeding events in the first 30 anticoagulation (e.g. enoxaparin 0.5 mg/kg i.v. or UFH 60 IU/kg)
days. Aspirin treatment did not impact on ischaemic event rates after • Aspirin is indicated but avoid pre-treatment with P2Y12 receptor
30 days and for up to 6 months, but did increase the bleeding risk during inhibitors
© ESC 2023
this time period.334,335 In the MASTER DAPT trial, 4579 HBR patients • GP IIb/IIIa receptor inhibitors only for bailout or peri-procedural
were allocated to 1 month vs. 6 months of DAPT after implantation of a complications
biodegradable-polymer sirolimus-eluting stent; half of the patients pre-
sented with ACS and a third were on OAC treatment.276 A sub-analysis GP, glycoprotein; INR, international normalized ratio; i.v., intravenous; NOAC, non-vitamin
K antagonist oral anticoagulant; OAC, oral anticoagulation/anticoagulant; PCI,
of this study reported that stopping DAPT after 1 month and stopping percutaneous coronary intervention; UFH, unfractionated heparin; VKA, vitamin K
single antiplatelet therapy (SAPT) after 6 months while maintaining antagonist.
ESC Guidelines 3761
Patients with ACS and an indication for OAC
Strategy to reduce
Default strategy
ischaemic riska
Time from ACS
0 weeks
TAT: (N)OAC + DAPT
(Class I) TAT: (N)OAC + DAPT
up to 1 week
(Class IIa)

up to 1 month
DAT: (N)OAC + SAPT
(Class I)
3 months
DAT: (N)OAC + SAPT

6 months
(Class I)
DAT: (N)OAC
(N)OAC + SAPT monotherapy
9 months
(Class I) (Class IIb)
12 months
(N)OAC monotherapy (N)OAC monotherapy
(Class I) (Class I)
Beyond
12 months
Figure 12 Antithrombotic regimens in patients with acute coronary syndrome and an indication for oral anticoagulation. ACS, acute coronary syndrome;
ARC-HBR, Academic Research Consortium for High Bleeding Risk; DAPT, dual antiplatelet therapy; DAT, dual antithrombotic therapy; NOAC, non-vitamin
K antagonist oral anticoagulant; OAC, oral anticoagulation/anticoagulant; SAPT, single antiplatelet therapy; TAT, triple antithrombotic therapy; VKA, vitamin K
antagonist. OAC: preference for a NOAC over VKA for the default strategy and in all other scenarios if no contraindications. For both TAT and DAT regimens,
the recommended doses for the NOACs are as follows: Apixaban 5 mg b.i.d., Dabigatran 110 mg or 150 mg b.i.d., Edoxaban 60 mg o.d., Rivaroxaban 15 mg or 20
mg o.d. NOAC dose reductions are recommended in patients based on certain criteria for each of the NOACs (including renal function, body weight, concomi-
tant medications and age). SAPT: preference for a P2Y12 receptor inhibitor (usually clopidogrel) over aspirin. See Bleeding risk assessment in Supplementary data
online, Section 8.2.2.3 for details on the ARC-HBR criteria. In addition, patients with a PRECISE-DAPT score of ≥25 are regarded as high bleeding risk. aSee
Supplementary material online, Table S9 for examples of high-risk features of stent-driven recurrent events.
At variance with the default strategy, DAT may be shortened to 6 in comparison to placebo, led to more bleeding events but no significant
months by withdrawing the antiplatelet therapy in certain patients; differences in death, hospitalization, or ischaemic events were observed.308
for example, in patients with multiple HBR factors. In patients with Regarding the need to continue with any antiplatelet agent beyond
high ischaemic risk or other anatomical/procedural characteristics 12 months after ACS and/or PCI in patients with an indication for
that outweigh the bleeding risk, TAT should be prolonged for up to OAC, the AFIRE (Atrial Fibrillation and Ischemic Events With
1 month, followed by DAT for up to 12 months. Rivaroxaban in Patients With Stable Coronary Artery Disease) trial
There is currently limited evidence to support the use of OAC with randomized 2236 AF patients treated with PCI or CABG more than
ticagrelor or prasugrel as DAT after ACS and/or PCI as an alternative to 1 year earlier or with documented CAD to receive either rivaroxaban
TAT; ticagrelor was used in 5–12% and prasugrel in 1–2% of patients, monotherapy or combination therapy with rivaroxaban plus a single
respectively, in the four pivotal RCTs.305,307–309,339 antiplatelet agent.324 Rivaroxaban monotherapy was non-inferior to
In medically managed ACS patients, current data support DAT over combination therapy for the primary efficacy composite endpoint of
TAT, with a single antiplatelet agent (most commonly clopidogrel) for at stroke, systemic embolism, MI, UA requiring revascularization, or over-
least 6 months.308 In the AUGUSTUS trial, ∼24% of enrolled patients pre- all death, and superior with regard to the primary safety endpoint of
sented with medically managed ACS.308 In these patients, apixaban signifi- major bleeding. This trial and another prematurely terminated trial sup-
cantly reduced bleeding events compared with a VKA, while no significant port the recommendation to stop antiplatelet therapy after 12 months
differences were observed in death or ischaemic events. The use of aspirin, and continue with OAC monotherapy in most patients.325
3762 ESC Guidelines
6.5.2. Patients requiring vitamin K antagonists or Recommendation Table 7 — Recommendations for

undergoing coronary artery bypass surgery fibrinolytic therapy
In patients for whom a VKA is mandated (e.g. patients with mechanical
prosthetic valves), DAT with a VKA and SAPT (preferably clopidogrel)
is indicated after an up to 1-week period of TAT (with aspirin and clo- Fibrinolytic therapy
pidogrel).306 A network meta-analysis has reported that compared
When fibrinolysis is the reperfusion strategy, it is
with TAT (consisting of VKA plus aspirin and clopidogrel), DAT
recommended to initiate this treatment as soon as
(VKA plus clopidogrel) was associated with a trend towards a reduction I A
possible after diagnosis in the pre-hospital setting
in TIMI major bleeding, with no significant difference observed in
(aim for target of <10 min to lytic bolus).206,353–355
MACE.336
In ACS patients undergoing CABG with an established indication for A fibrin-specific agent (i.e. tenecteplase, alteplase, or
I B
OAC, anticoagulation in combination with SAPT should be resumed reteplase) is recommended.356,357

after CABG as soon as possible and TAT should be avoided. A half-dose of tenecteplase should be considered in
IIa B
patients >75 years of age.184
6.6. Antithrombotic therapy as an adjunct Antiplatelet co-therapy with fibrinolysis
to fibrinolysis Aspirin and clopidogrel are recommended.340–342 I A

ISIS-2 (Second International Study Of Infarct Survival) demonstrated Anticoagulation co-therapy with fibrinolysis
that the benefits of aspirin and fibrinolytics (i.e. streptokinase) were Anticoagulation is recommended in patients treated
additive.340 The first dose of aspirin (162–325 mg) should be chewed with fibrinolysis until revascularization (if performed)
or given i.v. and a low dose (75–100 mg) given orally daily from the I A
or for the duration of hospital stay (up to 8
next day thereafter. Clopidogrel added to aspirin reduces the risk of days).260,347,348,350,357–360
CV events and overall mortality in patients treated with fibrinolysis
Enoxaparin i.v. followed by s.c. is recommended as
and should be added to aspirin following lytic therapy.341,342 Based I A
the preferred anticoagulant.347,348,357–360
on the available RCTs, there is insufficient evidence to support or refute
When enoxaparin is not available, UFH is
improved outcomes with ticagrelor or prasugrel in patients with STEMI
treated with thrombolytics.343–345 There is no evidence that adminis- recommended as a weight-adjusted i.v. bolus, I B
tration of GP IIb/IIIa receptor inhibitors improves myocardial perfusion followed by infusion.357
© ESC 2023
or outcomes in patients treated with fibrinolysis, and it may increase In patients treated with streptokinase, an i.v. bolus of
the risk of bleeding events.346 fondaparinux followed by an s.c. dose 24 h later IIa B
Parenteral anticoagulation is recommended until revascularization, if should be considered.260
performed. Despite an increased risk of major bleeding, the net clinical
i.v., intravenous; s.c, subcutaneous; UFH, unfractionated heparin.
benefit favoured enoxaparin over UFH in the ASsessment of the a
Safety and Efficacy of a New Thrombolytic 3 (ASSENT 3) trial (n = b
Level of evidence.
6095).347 In the large Enoxaparin and Thrombolysis Reperfusion for
Acute myocardial infarction Treatment–Thrombolysis In Myocardial
Infarction 25 (ExTRACT–TIMI 25) trial (n = 20 506), a lower dose 6.7. Antithrombotic therapy in patients
of enoxaparin was given to patients ≥75 years old and to those not undergoing reperfusion
with impaired renal function (estimated creatinine clearance Patients with a final diagnosis of ACS who do not undergo reperfusion
<30 mL/min). Enoxaparin was associated with a reduction in the should receive a P2Y12 receptor inhibitor in addition to aspirin, maintained
risk of death and re-infarction at 30 days when compared with a over 12 months unless there is HBR. Among ACS patients who are med-
weight-adjusted UFH dose, but at the cost of a significant increase ically managed without revascularization, the combination of aspirin and ti-
in non-cerebral bleeding complications. The net clinical benefit (i.e. ab- cagrelor for up to 12 months has demonstrated a benefit in comparison to
sence of death, non-fatal infarction, and intracranial haemorrhage) fa- aspirin and clopidogrel.238,361 The combination of aspirin and prasugrel can
voured enoxaparin.348,349 In the large OASIS-6 trial, fondaparinux was also be justified in preference to aspirin and clopidogrel if coronary angiog-
superior to placebo or UFH in preventing death and re-infarction, es- raphy has been performed and CAD is confirmed.239,362 As such, potent
pecially in patients who received streptokinase.260,350 In a large trial P2Y12 inhibitor-based DAPT is a reasonable option for patients with a final
with streptokinase, significantly fewer re-infarctions were seen with bi- diagnosis of ACS not undergoing reperfusion, unless concerns over the
valirudin given for 48 h compared with UFH, although at the cost of a bleeding risk prevail (e.g. based on ARC-HBR criteria).238,361 A DAPT regi-
modest non-significant increase in non-cerebral bleeding complica- men based on clopidogrel and aspirin may provide a good net clinical bene-
tions.351 Bivalirudin has not been studied with fibrin-specific agents, fit among older ACS patients.242,363 Further information regarding
and there is no evidence to support direct thrombin inhibitors as an antithrombotic therapy in ACS patients who do not undergo reperfusion
adjunct to fibrinolysis.260,350 is provided in the Supplementary data online.
Weight-adjusted i.v. tenecteplase, low-dose aspirin, clopidogrel given
orally, and enoxaparin i.v. followed by s.c. administration until the time
of PCI (revascularization) represents the most extensively studied 7. Acute coronary syndrome with
antithrombotic regimen as part of a pharmaco-invasive strat-
egy.184,186,213,346,352 Further information on fibrinolytic therapy, includ-
unstable presentation
ing antithrombotic co-therapies and contraindications is provided in In some cases, ACS patients can present with haemodynamic com-
Supplementary data online, Tables S10 and S11. promise (i.e. out-of-hospital cardiac arrest [OHCA] and/or CS).
ESC Guidelines 3763
7.1. Out-of-hospital cardiac arrest in acute respect to the primary endpoint (death, severe disability, or coma) at
90 days.384 In all comatose survivors, evaluation of neurological progno-
coronary syndrome sis no earlier than 72 h after admission is recommended.367,378–383,386
While a small minority of all patients with ACS present as OHCA, ACS
is the most common cause of OHCA.364–366 In patients with OHCA,
resuscitation efforts should follow the European Resuscitation 7.1.1. Systems of care
Council Guidelines.367 The majority of adult cardiac arrest cases are There is increasing evidence suggesting that specialized hospitals for pa-
associated with obstructive CAD and ACS should be included in the tients following OHCA (referred to as cardiac arrest centres) may be
differential diagnosis.365,368 Therefore, ICA can be part of the post- associated with clinical benefits.367 See Supplementary data online,
resuscitation management for patients who are estimated to have a Section 7.1.1 for expanded information on this topic.
high probability of acute coronary occlusion (e.g. persistent
ST-segment elevation or equivalents and/or haemodynamic and/or
electrical instability).367,369 Neurological status (e.g. comatose vs. non- Recommendation Table 8 — Recommendations for

cardiac arrest and out-of-hospital cardiac arrest
comatose) and survival probability (i.e. favourable benefit/risk ratio vs.
futility) should also be included in the decision-making algorithm.
Despite the lack of dedicated trials, patients with return of spontan-
eous circulation (ROSC) and persistent ST-segment elevation should, in Cardiac arrest and OHCA
general, undergo a PPCI strategy (immediate ICA and PCI if indicated), A PPCI strategy is recommended in patients with
based on the overall clinical situation and a reasonable benefit/risk ratio.
resuscitated cardiac arrest and an ECG with
Based on registry reports, emergent ICA and PCI are associated with I B
persistent ST-segment elevation (or
good outcomes in this setting, particularly in patients who are non-
equivalents).368,387,388
comatose at initial assessment.368,370,371
Routine immediate angiography after resuscitated
The management of patients with ROSC without evidence of
ST-segment elevation should be individualized according to haemo- cardiac arrest is not recommended in
III A
dynamic and neurological status. In OHCA with an initial shockable haemodynamically stable patients without persistent
373–377
rhythm and without ST-segment elevation or equivalents and without ST-segment elevation (or equivalents).
CS, routine immediate ICA is not superior to a delayed invasive strategy Temperature control
based on data from the COACT (Coronary Angiography after Cardiac Temperature control (i.e. continuous monitoring of
Arrest) and TOMAHAWK (Immediate Unselected Coronary core temperature and active prevention of fever [i.e.
Angiography Versus Delayed Triage in Survivors of Out-of-hospital >37.7°C]) is recommended after either
Cardiac Arrest Without ST-segment Elevation) RCTs.372,373 Smaller, I B
out-of-hospital or in-hospital cardiac arrest for adults
underpowered trials (EMERGE [EMERGEncy versus delayed coronary
who remain unresponsive after return of
angiogram in survivors of out-of-hospital cardiac arrest with no obvious
spontaneous circulation.378–385,389
non-cardiac cause of arrest], PEARL [A Pilot Randomized Clinical Trial
of Early Coronary Angiography Versus No Early Coronary Systems of care
Angiography for Post-Cardiac Arrest Patients Without ECG ST It is recommended that healthcare systems
Segment Elevation], and COUPE [Coronariography in OUt of implement strategies to facilitate transfer of all
hosPital Cardiac arrEst]) have also pointed to the same conclu- patients in whom ACS is suspected after resuscitated I C
sion.372–377 Further detail on these trials is provided in the cardiac arrest directly to a hospital offering 24/7 PPCI
Supplementary data online, Evidence Tables. via one specialized EMS.390–392
Based on data from the COACT and TOMAHAWK trials, it appears Transport of patients with OHCA to a cardiac arrest
reasonable to delay ICA in haemodynamically stable patients with re- centre according to local protocols should be IIa C
suscitated OHCA without ST-segment elevation or equivalents. Initial
considered.391,393
evaluation in the ED or intensive cardiac care unit (ICCU) should focus
on excluding non-coronary causes (cerebrovascular events, respiratory Evaluation of neurological prognosis
failure, non-cardiogenic shock, PE, or intoxication). Echocardiography is
© ESC 2023
Evaluation of neurological prognosis (no earlier than
also useful in the evaluation of these patients. The decision to perform 72 h after admission) is recommended in all I C
selective coronary angiography (and PCI if indicated) should also con- comatose survivors after cardiac arrest.386
sider factors associated with poor neurological outcome and the likeli-
ACS, acute coronary syndrome; ECG, electrocardiogram; EMS, emergency medical
hood of ACS. services; OHCA, out-of-hospital cardiac arrest; PPCI, primary percutaneous coronary
In patients who remain unresponsive after ROSC, monitoring of intervention.
a
core temperature and actively preventing fever (defined as a tempera- b
Level of evidence.
ture >37.7°C) is recommended to improve neurological out-
come.367,378–385 A recent study compared device-based temperature
control of 36°C for 24 h followed by targeting of 37°C for either 12
or 48 h (for total intervention times of 36 and 72 h, respectively) or un- 7.2. Cardiogenic shock complicating acute
til the patient regained consciousness in 789 patients with OHCA of a coronary syndrome
presumed cardiac cause (∼45% with ST segment elevation on ECG; im- Early revascularization with either PCI or CABG is recommended for
mediate coronary angiography performed in 92% and PCI in 43%). This patients with AMI complicated by CS, based on the results of the
study reported comparable outcomes with both strategies with SHOCK (Should We Emergently Revascularize Occluded Coronaries
3764 ESC Guidelines
for Cardiogenic Shock) trial.394–396 While most patients will proceed to In patients with ACS and severe/refractory CS,
PCI at the time of diagnostic angiography if myocardial revascularization short-term mechanical circulatory support may be IIb C
is indicated, surgical revascularization represents a valuable treatment considered. 402
option in patients in whom attempted PCI of the IRA has failed or if
© ESC 2023
The routine use of an IABP in ACS patients with CS
the coronary anatomy is not amenable to PCI.395,397,398 In the presence and without mechanical complications is not III B
of CS due to AMI-related mechanical complications, surgical or percu-
recommended.399,405–407
taneous treatment may also be indicated and the strategy should be
decided based on discussion between members of the Heart Team. ACS, acute coronary syndrome; CABG, coronary artery bypass grafting; CS, cardiogenic
shock; IABP, intra-aortic balloon pump; IRA, infarct-related artery; PPCI, primary
In the IABP-SHOCK II (Intraaortic Balloon Pump in Cardiogenic Shock
percutaneous coronary intervention; STEMI, ST-elevation myocardial infarction.
II) trial, intra-aortic balloon pump (IABP) use was not associated with a
lower 30-day mortality.399 Therefore, in the absence of mechanical com- b
Level of evidence.
plications, the routine use of an IABP is not recommended for CS com-
plicating AMI. The role of mechanical circulatory devices (veno-arterial

extracorporeal membrane oxygenation [VA-ECMO], micro-axial 8. Management of acute coronary
pump) in the AMI setting is not well established and large-scale rando-
mized trials are warranted.400,401 The Extracorporeal Membrane syndrome during hospitalization
Oxygenation in the Therapy of Cardiogenic Shock trial randomized
122 patients (51% with STEMI) with rapidly deteriorating or severe CS
8.1. Coronary care unit/intensive cardiac
to either immediate implementation of VA-ECMO or an initially conser- care unit
vative strategy (which allowed for downstream use of VA-ECMO).402 Following reperfusion, it is recommended to admit high-risk ACS pa-
The immediate implementation of VA-ECMO did not result in improved tients (including all STEMI patients) to a coronary care unit (CCU) or
clinical outcomes.402 However, the interpretation of this trial is challen- ICCU. Conditions in patients with ACS that act as acute risk modifiers
ging because of the ∼40% crossover rate to VA-ECMO in the conserva- include ongoing myocardial ischaemia (e.g. failed reperfusion), acute HF
tive arm, the inclusion of heterogenous phenotypes of CS, and inclusion and/or hypoperfusion, CS, cardiac arrest with coma, malignant (life-
of crossover in the combined primary endpoint. As a result of these lim- threatening) cardiac arrhythmias, high-degree atrioventricular block,
itations, this trial cannot adequately answer if mechanical circulatory sup- and acute renal failure (with oliguria). All ICCUs must have appropriate
port (MCS) is able to reduce mortality in this setting. diagnostic facilities to guide the delivery of pharmacological and invasive
It is important to note that while there is still a lack of high-quality treatment. The staff should be thoroughly familiar with the manage-
randomized data supporting the use of MCS in ACS patients presenting ment of all aspects of ACS, including: arrhythmias, HF, mechanical
with CS, some recent observational analyses have reported that the use circulatory support, invasive and non-invasive haemodynamic monitor-
of intravascular LV assist devices may be associated with an increased ing (arterial and pulmonary artery pressures), respiratory monitoring,
risk of adverse events in comparison to IABP in this setting, including mechanical ventilation, and temperature control.408 The CCU/ICCU
mortality and bleeding.401,403 Therefore, while MCS may be considered should also be able to manage patients with renal and pulmonary dis-
in selected patients with ACS and severe/refractory CS, caution should ease. The desirable organization, structure, and criteria of CCU/
be exercised in this regard until further randomized data are available. ICCUs have been detailed in an ESC–Acute CardioVascular Care
The management of patients with CS complicating AMI and MVD is Association position paper.408
presented in Section 10.
8.1.1. Monitoring
It is recommended to initiate ECG monitoring as soon as possible in all
patients with ACS in order to detect life-threatening arrhythmias and al-
Recommendation Table 9 — Recommendations for low prompt defibrillation if indicated. ECG monitoring for arrhythmias
cardiogenic shock and new ST-segment elevation/depression is recommended for at least
24 h after symptom onset in all high-risk patients with ACS, including
Recommendations Classa Levelb all STEMI patients.409 Longer monitoring could be considered in patients
at intermediate to high risk of cardiac arrhythmias (i.e. those with more
Immediate coronary angiography and PCI of the IRA
than one of the following criteria: haemodynamically unstable, presenting
(if indicated) is recommended in patients with CS I B
with major arrhythmias, left ventricular ejection fraction [LVEF] <40%,
complicating ACS.394,396,404
failed reperfusion, additional critical coronary stenoses of major vessels,
Emergency CABG is recommended for ACS-related or complications related to PCI). Further monitoring for arrhythmias will
I B
CS if PCI of the IRA is not feasible/unsuccessful.394,395 be dependent on the estimated risk. When a patient leaves the ICCU or
In cases of haemodynamic instability, emergency equivalent, monitoring may be continued by telemetry. It is recom-
surgical/catheter-based repair of mechanical mended that personnel adequately equipped and trained to manage life-
I C
complications of ACS is recommended, based on threatening arrhythmias and cardiac arrest accompany patients who are
Heart Team discussion. transferred between facilities during the time window in which they re-
Fibrinolysis should be considered in STEMI patients quire continuous rhythm monitoring.409
presenting with CS if a PPCI strategy is not available
IIa C
within 120 min from the time of STEMI diagnosis and 8.1.2. Ambulation
mechanical complications have been ruled out.184,354 Early ambulation (i.e. out of bed on day 1) is recommended in the ma-
Continued jority of patients with ACS. This is facilitated by using radial access for
ESC Guidelines 3765
invasive management. Patients with extensive myocardial damage, HF, 8.2.2.2. Imaging risk assessment
hypotension, or arrhythmias may initially rest in bed before assessment LV dysfunction is a key prognostic factor for patients with ACS.426 It is
of myocardial function and clinical stabilization. Prolongation of bed rest recommended that the LVEF is determined before hospital discharge in
and limitation of physical activity may occasionally be required in pa- all patients with ACS. Routine echocardiography after PPCI is recom-
tients with large infarcts or severe complications. mended to assess resting LV, RV, and valvular function. In addition,
echocardiography can be used to exclude early post-infarction mechan-
ical complications and LV thrombus. In the limited number of cases in
8.1.3. Length of stay in the intensive cardiac care unit which echocardiography is suboptimal or inconclusive, CMR may be
The optimal length of stay in the ICCU and hospital should be individua- a valuable alternative.427–431
lized according to the patient’s clinical situation, taking into account In patients presenting days after an acute ACS event with a com-
their baseline cardiac risk and comorbidities, baseline mental/functional pleted MI, the presence of recurrent angina or documented ischaemia
status, and social support.410,411 Of note, the majority of adverse in- and proven viability in a large myocardial territory may help to guide the
hospital events occur early after admission and the initiation of

strategy of planned revascularization of an occluded IRA.192,432,433
treatment. In patients with a pre-discharge LVEF of ≤40%, re-evaluation of the
LVEF 6–12 weeks after complete revascularization and optimal medical
therapy is recommended to assess the potential need for primary pre-
8.2. In-hospital care vention implantable cardioverter defibrillator (ICD) implantation.434
8.2.1. Length of hospital stay Additional parameters that are measured by imaging in these patients
The impact of both successful reperfusion and knowledge of the coron- and that have been used as endpoints in clinical trials include: (i) infarct
ary anatomy (due to increasing rates of ICA) has resulted in progressive size (CMR, SPECT, and positron emission tomography); (ii) myocar-
reductions in the length of stay after ACS, alongside significant reduc- dium at risk (SPECT, CMR); (iii) MVO (CMR); and (iv) intra-myocardial
tions in 30-day mortality, suggesting that discharge within 72 h is not as- haemorrhage (CMR). Infarct size, MVO and intra-myocardial haemor-
sociated with late mortality.411–417 Candidates for early discharge after rhage are predictors of both long-term mortality and HF in STEMI sur-
PCI can be identified using simple criteria.413,414 In one study, patients vivors.435–438
meeting the following criteria were considered to be ‘low risk’ and suit-
able for early discharge: age <70 years, LVEF >45%, one- or two-vessel
8.2.2.3. Biomarkers for risk assessment
disease, successful PCI, and no persistent arrhythmias.413 A recently
published consensus document also presents a template and flow chart Beyond diagnostic utility, initial cTn levels add prognostic information in
to support reasonable decision-making regarding post-procedural addition to clinical and ECG variables in terms of predicting the risk of
length of stay for a broad spectrum of patients undergoing PCI.418 short- and long-term mortality. While hs-cTn T and I have comparable
Early (i.e. same day) transfer to a local hospital following successful diagnostic accuracy, hs-cTn T has slightly greater prognostic accuracy
PPCI is routine practice. This can be done safely under adequate mon- regarding mortality.61,439–441 Serial measurements are useful to identify
itoring and supervision in selected patients (i.e. patients without signs or peak levels of cTn for risk stratification purposes in patients with estab-
symptoms consistent with ongoing myocardial ischaemia, without ar- lished MI. The higher the hs-cTn levels, the greater the risk of
rhythmias, who are haemodynamically stable, who are not requiring death.31,55,442 However, evidence is limited regarding the optimal
vasoactive or mechanical support, and who are not scheduled for fur- time points of serial hs-cTn measurement. Serum creatinine and
ther revascularization).419 eGFR should also be determined in all patients with ACS because
they affect prognosis and are key elements of the GRACE risk score.443
Similarly, natriuretic peptides (brain natriuretic peptide [BNP] and
8.2.2. Risk assessment N-terminal pro-BNP [NT-pro BNP]) provide prognostic information
Early and late risk stratification soon after presentation is useful to aid in addition to cTn regarding the risk of death and acute HF, and the de-
decision-making in patients presenting with ACS. velopment of AF.444 Additional information on the use of biomarkers
for this purpose is presented in the Supplementary data online.
8.2.2.1. Clinical risk assessment 8.2.2.4. Bleeding risk assessment

All patients with ACS (in particular, patients with STEMI) should have
Major bleeding events are associated with increased mortality in pa-
an early assessment of short-term risk, including an evaluation of the ex-
tients with ACS.231 Further detail on scores that may be considered
tent of myocardial damage, the achievement of successful reperfusion,
for estimation of bleeding risk is provided in the Supplementary data
and the presence of clinical markers of high risk of further events (i.e.
online, including Table S12.
older age, tachycardia, hypotension, Killip class >I, anterior MI, previous
MI, elevated initial serum creatinine, history of HF, peripheral arterial
disease or anaemia). Several risk scores have been developed based 8.2.2.5. Integrating ischaemic and bleeding risks
on readily identifiable parameters in the acute phase before reperfu- Major bleeding events affect prognosis in a similar way to spontaneous
sion.420,421 A number of prognostic models that aim to estimate the ischaemic complications.445,446 Given the trade-off between ischaemic
longer-term risk of all-cause mortality, or the combined risk of all-cause and bleeding risks for any antithrombotic regimen, risk scores may be
mortality or MI, have also been developed. These models have been useful to tailor antithrombotic duration and intensity, in order to maxi-
formulated into clinical risk scores and, among these, the GRACE risk mize ischaemic protection and minimize bleeding risk in the individual
score offers the best discriminative performance and is therefore re- patient. Specific risk scores have been developed for patients on
commended for risk assessment.48,421–425 Additional information re- DAPT following PCI, in the settings of both CCS and ACS. Further de-
garding the GRACE score is provided in the Supplementary data online. tail on available scores is provided in the Supplementary data online.
3766 ESC Guidelines
Recommendation Table 10 — Recommendations for associated with an increased bleeding risk, which affects prognosis
in-hospital management at least as much as ischaemic complications and is associated with im-
paired survival.448,449 Among patients undergoing PCI, access-related
Recommendations Classa Levelb bleeding accounts for 30–70% of total bleeding events.450 There is
strong evidence demonstrating that reducing access-site bleeding
Logistical issues for hospital stay
events with the use of radial access translates into significant clinical
It is recommended that all hospitals participating in benefits.448,449 The largest randomized trials on this topic in patients
the care of high-risk patients have an ICCU/CCU with ACS are the RadIal Vs femorAL access for coronary intervention
equipped to provide all required aspects of care, I C (RIVAL) trial with 7021 ACS patients and the Minimizing Adverse
including treatment of ischaemia, severe heart failure, Haemorrhagic Events by TRansradial Access Site and Systemic
arrhythmias, and common comorbidities. Implementation of angioX (MATRIX) trial with 8404 ACS patients
It is recommended that high-risk patients (including all (47.6% with STEMI).451,452 These trials have demonstrated signifi-
cantly lower rates of access site-related bleeding, surgical access

STEMI patients and very high-risk NSTE-ACS I C
patients) have ECG monitoring for a minimum of 24 h. site repair, and blood transfusion with radial compared with femoral
It is recommended that high-risk patients with access. In the MATRIX trial, no significant interaction was observed
successful reperfusion therapy and an uncomplicated between the type of ACS and the benefit associated with the radial
clinical course (including all STEMI patients and very approach, suggesting that the results of this trial can be extended
high-risk NSTE-ACS patients) are kept in the CCU/ I C to patients across the entire spectrum of ACS.453 In a cost-
ICCU for a minimum of 24 h whenever possible, after
effectiveness analysis of the MATRIX trial, radial access was also as-
sociated with significant savings in terms of quality-adjusted life years
which they may be moved to a step-down monitored
and PCI-related costs.454 Therefore, radial access is recommended as
bed for an additional 24–48 h.
the preferred approach in ACS patients undergoing invasive assess-
Discharge of selected high-risk patients within 48–
ment with or without PCI. However, femoral access may still be se-
72 h should be considered if early rehabilitation and IIa A
lectively chosen instead of radial access in certain patients (i.e.
adequate follow-up are arranged.411,413,415,447 depending on the haemodynamic situation and other technical as-
Same-day transfer in selected stable patients after pects during the index PCI procedure).
successful and uneventful PCI should be IIa C
considered.419
Imaging
9.1.2. Intravascular imaging/physiology of the
Routine echocardiography is recommended during infarct-related artery
hospitalization to assess regional and global LV
I C 9.1.2.1. Intravascular imaging
function, detect mechanical complications, and As a diagnostic tool, intravascular imaging is useful in ACS patients
exclude LV thrombus.
© ESC 2023
without significant obstructive CAD on coronary angiography.

When echocardiography is suboptimal/inconclusive, Excluding an atherothrombotic cause in the main coronary arteries
IIb C
CMR imaging may be considered. for the ACS may have important clinical implications, not only for im-
mediate invasive management but also for potentially lifelong
ACS, acute coronary syndrome; CCU, cardiac care unit; CMR, cardiac magnetic resonance;
ECG, electrocardiogram; ICCU, intensive cardiac care unit; LV, left ventricular; NSTE-ACS, antithrombotic therapies. Intravascular imaging is also useful in cases
non-ST-segment elevation acute coronary syndrome; PCI, percutaneous coronary where there is ambiguity regarding the culprit lesion. Culprit lesion
intervention; STEMI, ST-elevation myocardial infarction. ambiguity can be present in more than 30% of patients with sus-
a
b
Level of evidence.
pected NSTE-ACS and over 10% of patients may have multiple cul-
prit lesions.455,456 The recommendations for intravascular imaging
in ACS are presented in Figure 13.
9. Technical aspects of invasive The role of intravascular imaging is well established as a tool to guide
and optimize PCI. Evidence in support of intravascular ultrasound
strategies (IVUS) guidance in ACS generally derives from subgroup analyses of all-
comers trials. Meta-analysis of available randomized trials confirms the
9.1. Percutaneous coronary intervention superiority of IVUS guidance in the reduction of MACE, although a de-
9.1.1. Vascular access finitive, large-scale, multinational trial is missing.457–459 Smaller RCTs
Timely PCI with concomitant antithrombotic drugs has reduced the have evaluated the role of optical coherence tomography (OCT)
ischaemic risk in patients with ACS. However, this strategy is also (see Supplementary data online).460
ESC Guidelines 3767
Working diagnosis: ACS
Coronary angiography

Potential ambiguous
angiographic findings
Clear culprit lesion,
No clear culprit lesion Multivessel disease
suitable for PCI
Hazy lesion/calcification
Tortuosity/eccentricity
Intravascular imaging
Potential intravascular
IVUS or OCT Intravascular imaging
imaging findings
Intravascular imaging (preferably OCT) in
to guide PCI patients with ambiguous Coronary plaque pathology
(Class lla) culprit lesions Erosion Nodule Rupture
(Class llb)
SCAD No lesion
Treat as per
imaging findings
Potential further
investigations
Consider further Left ventriculography
PCI of culprit lesion
investigations as required
Echocardiography
Cardiac MRI
Figure 13 A practical algorithm to guide intravascular imaging in acute coronary syndrome patients. ACS, acute coronary syndrome; IVUS, intravascular
ultrasound; MRI, magnetic resonance imaging; OCT, optical coherence tomography; PCI, percutaneous coronary intervention; SCAD, spontaneous coronary
artery dissection.
9.1.2.2. Intravascular physiology role of intracoronary physiology in the IRA is presented in the
Intracoronary physiology is increasingly being used in patients with Supplementary data online.
ACS to assess the haemodynamic significance of intermediate severity
non-IRA stenoses (see Section 10). However, PCI of the IRA should
not be deferred based on invasive epicardial functional assessment 9.1.3. Timing of revascularization with percutaneous
in patients with ACS. The coronary microcirculation begins to re- coronary intervention
cover within 24 h of PPCI and acute functional assessment of the In some patients with ACS undergoing ICA, an initial conservative man-
IRA may underestimate the true haemodynamic severity of the cor- agement strategy with optimized guideline-directed medical therapy
onary stenosis.461 Beyond 1 week from the acute event, fractional may be considered on a case-by-case basis. The specific circumstances
flow reserve (FFR) measurement has been reported to reliably predict include ACS patients with small calibre vessels, an occluded small side
abnormal nuclear imaging results.462 Additional information about the branch, or concerns regarding non-compliance with antithrombotic
3768 ESC Guidelines
therapy. In the context of complex CAD and anticipated complex PCI, aspiration is not recommended, but in cases of large residual thrombus
an initial conservative strategy in medically stabilized patients without burden after opening the vessel with a guide wire or a balloon, throm-
ongoing symptoms allows time for Heart Team discussion regarding bus aspiration may be considered.
the optimal revascularization strategy.
9.1.5.2. Interventions to protect the microcirculation
9.1.4. Balloons and stents The damage inflicted on the myocardium during AMI is the result of is-
New-generation DES are associated with superior safety and improved chaemia and subsequent reperfusion (ischaemia/reperfusion injury). In
efficacy compared with bare metal stents (BMS) and first-generation patient-level pooled analyses, infarct size and MVO are independent
DES. The Norwegian Coronary Stent Trial (NORSTENT)—the largest predictors of long-term mortality and HF in survivors of
clinical trial comparing outcomes of patients treated with new- STEMI.436,478 Strategies to reduce ischaemia/reperfusion injury in gen-
generation DES or BMS—reported that the primary endpoint of death eral (and MVO in particular) remain an unmet clinical need. Further in-
or MI was comparable in both treatment groups. Both target lesion re- formation regarding interventions to protect the microcirculation that

vascularization (TLR) and stent thrombosis were reduced in the DES are under clinical or experimental investigation is presented in the
group and there was no treatment effect by ACS presentation inter- Supplementary data online.
action for the primary endpoint.463 The COMFORTABLE-AMI
(Comparison of Biolimus Eluted From an Erodible Stent Coating 9.2. Coronary artery bypass grafting
With Bare Metal Stents in Acute ST-Elevation Myocardial Infarction) 9.2.1. Indication and timing of coronary artery bypass
and EXAMINATION (Everolimus-Eluting Stents Versus Bare-Metal grafting in acute coronary syndrome patients
Stents in ST Segment Elevation Myocardial Infarction) trials have also
There are no dedicated RCTs comparing percutaneous vs. surgical re-
reported the clinical superiority of DES over BMS in terms of lower
vascularization in patients with ACS. In the setting of STEMI, CABG
rates of re-infarction, target lesion revascularization, and stent throm-
should be considered only when PPCI is not feasible, particularly in
bosis.464,465 This clinical benefit was preserved at longer-term follow-
the presence of ongoing ischaemia or large areas of jeopardized
up.466–468
myocardium.479
A strategy of drug-coated balloon (DCB) angioplasty without
In patients requiring immediate revascularization in the setting of
stenting has also been proposed for patients with NSTE-ACS. In the
very high-risk NSTE-ACS, PCI is usually preferred for reasons of time-
small, prospective, randomized, single-centre REVELATION
liness, unless concomitant mechanical complications dictate a prefer-
(REVascularization With PaclitaxEL-Coated Balloon Angioplasty
ence for surgical intervention.
Versus Drug-Eluting Stenting in Acute Myocardial InfarcTION) trial,
In other patients with ACS, the choice of revascularization modality
DCB PCI vs. DES PCI was investigated in 120 patients undergoing
should be made according to the number of diseased vessels and the gen-
PPCI. The primary endpoint of target vessel FFR at 9 months was
eral principles of myocardial revascularization.250 In patients with MVD,
not significantly different between the two groups.469 In the small
the choice of revascularization modality will be influenced by the overall
PEPCAD NSTEMI (Bare Metal Stent Versus Drug Coated Balloon
anatomical disease complexity and the presence of comorbidities (includ-
With Provisional Stenting in Non-ST-Elevation Myocardial Infarction)
ing diabetes) in patients with low predicted surgical risk and mortality who
trial, 210 patients were randomized to compare a DCB with primary
are considered suitable for either modality. This is based on data from two
stent treatment (BMS or DES).470 During a mean follow-up period of
large-scale individual patient meta-analyses.480,481
9.2 months, DCB treatment was non-inferior to treatment with a stent,
with a target lesion failure (primary study endpoint) rate of 3.8% vs.
6.6% (P = 0.53). Given the limitations of these studies (in particular, 9.2.2. Technical considerations specific to acute
the relatively small sample sizes), the use of DCB in NSTE-ACS requires coronary syndrome patients
further investigation in order to better inform future guideline The patient profile, including the need for emergency or extremely ex-
recommendations.471 peditious revascularization, may influence both the technique of CABG
(including on-pump beating heart CABG) and the choice and use of
CABG conduits. The need for prompt surgical revascularization in
9.1.5. Embolic protection and microvascular salvage
emergency circumstances does not facilitate the use of full arterial re-
strategies
vascularization due to the prolonged period required for graft harvest-
9.1.5.1. Thrombus aspiration
ing. Accordingly, the use of total venous graft-based CABG or the use
Large RCTs have failed to demonstrate a clinical benefit with routine of single left internal mammary artery plus additional venous grafts may
manual thrombus aspiration in comparison to conventional PPCI.472– be useful in this setting.397
474
In an individual patient data meta-analysis, thrombus aspiration
was associated with fewer CV deaths and with more strokes or transi-
ent ischaemic attacks in the subgroup of patients with high thrombus 9.3. Spontaneous coronary artery
burden (TIMI thrombus Grade 3).475 However, in a sub-analysis from dissection
TOTAL (a Trial of routine aspiration ThrOmbecTomy with PCI vs. Spontaneous coronary artery dissection (SCAD) is an infrequent cause
PCI ALone in patients with STEMI), routine thrombus aspiration did of ACS in general but accounts for a significant proportion of ACS cases
not improve outcomes at 1 year and was also associated with an in- in young/middle-aged women.482 The pathophysiology underlying SCAD
creased rate of stroke in patients with high thrombus burden.476 In pa- is different to that of Type 1 MI and there are some differences in its man-
tients with NSTE-ACS and thrombus-containing lesions, PCI with agement and outcomes. For these reasons, it is of paramount importance
adjunctive thrombus aspiration was not associated with a reduction that an accurate diagnosis is established. Until evidence from ongoing
in MVO 4 days after the index procedure or with fewer MACE after prospective trials becomes available, patients with SCAD should receive
up to 1 year of follow-up.477 Based on these data, routine thrombus the same pharmacological therapy as other ACS patients.483
ESC Guidelines 3769
9.3.1. Intravascular imaging Drug-eluting stents are recommended in preference

I A
There are no RCTs to guide management strategies in patients with to bare metal stents in all cases.463,466,468
SCAD. The use of intravascular imaging is based on observations re- In patients with spontaneous coronary artery
ported from clinical cohort studies and expert opinion.482,484,485 In dissection, PCI is recommended only for patients
cases of diagnostic uncertainty after angiography, the use of intracor- with symptoms and signs of ongoing myocardial I C
onary imaging with OCT or IVUS has to be carefully considered. ischaemia, a large area of myocardium in jeopardy,
There should be sufficient diagnostic uncertainty to justify coronary and reduced antegrade flow.
instrumentation, and even if this is the case, other factors like vessel
Intravascular imaging should be considered to guide
tortuosity, vessel diameter, and a distal lesion location may prohibi- IIa A
PCI.495–499
tively increase the risk.482 If the decision is made to perform intravas-
Coronary artery bypass grafting should be
cular imaging, it is imperative to ensure the guide wire is located within
considered in patients with an occluded IRA when
the true lumen of the coronary artery before advancing the imaging IIa C
PPCI is not feasible/unsuccessful and there is a large

catheter.482 In patients with a diagnosis of SCAD on angiography
and a plan for medical therapy, additional coronary instrumentation area of myocardium in jeopardy.
and intravascular imaging is not recommended on safety Intravascular imaging (preferably optical coherence
grounds.482,484,485 tomography) may be considered in patients with IIb C
ambiguous culprit lesions.
© ESC 2023
9.3.2. Revascularization The routine use of thrombus aspiration is not
III A
Conservative medical management, as opposed to PCI, is generally re- recommended.472–474
commended for patients with SCAD.482 In an international case series, IRA, infarct-related artery; PCI, percutaneous coronary intervention; PPCI, primary
coronary complications following PCI occurred in >30% of pa- percutaneous coronary intervention.
a
tients.486–488 In a pooled analysis of three SCAD-PCI cohorts including b
Level of evidence.
215 patients (94% female) drawn from Dutch, Spanish, and UK regis-
tries, and a matched cohort of conservatively managed SCAD patients
(n = 221), PCI was associated with complications in ≈40% of cases (in-
cluding 13% with serious complications). PCI is recommended only for
10. Management of patients with
SCAD with associated symptoms and signs of ongoing myocardial is- multivessel disease
chaemia, a large area of myocardium in jeopardy, and reduced ante-
Approximately half of ACS patients have coronary MVD.500
grade flow. Useful strategies for these patients may include minimal
Management of non-IRA disease varies depending on the clinical
plain balloon angioplasty to restore flow, followed by a conservative
setting.
strategy, targeted stenting to seal the proximal and distal ends of the
dissection, and/or extended stent lengths to prevent propagation of
the haematoma. In patients with SCAD, CABG is recommended 10.1. Management of multivessel disease in
when dissection affects the left main or two proximal vessels, if PCI acute coronary syndrome complicated by
is not feasible or unsuccessful, and if there are symptoms and signs of cardiogenic shock
ongoing myocardial ischaemia. In a small observational study, patients
Cardiogenic shock may occur in up to 4–11% of ACS patients, and oc-
with SCAD treated with CABG had favourable early clinical outcomes,
curs more frequently in the presence of complete coronary occlu-
with an event rate up to 5 years similar to that of patients treated con-
sion.501,502 Ischaemia-related HF, acute severe mitral regurgitation,
servatively, despite a significant (68%) rate of graft occlusion at 5
and mechanical complications are the major precipitating causes of
years.486 The rate of graft occlusion over time can be explained by
CS in ACS. Irrespective of the mode of presentation (i.e. with or with-
the fact that CABG in these patients may be technically challenging as
out ST-segment elevation or equivalent ECG patterns), these patients
the dissected coronary artery is more prone to anastomosis failure,
should be transferred as soon as possible to a tertiary care centre (e.g. a
and because spontaneous healing over time may restore the flow in
shock centre) where ICA can be performed, supported by specialists
the anastomosed vessel.486,489 For this reason, vein grafts should be
with relevant experience (the Shock Team).503,504
considered in these patients in order to preserve arterial conduits for
In the SHOCK trial, which compared emergency revascularization
future use.485
with initial medical stabilization in 302 patients with acute MI compli-
cated by CS, ∼60% had anterior MI and 85% had MVD.394 Among
Recommendation Table 11 — Recommendations for the patients assigned to emergency revascularization, 64% underwent
technical aspects of invasive strategies PCI and 36% underwent CABG. There were no differences in mortality
at 30 days (primary endpoint), but at 6 months mortality was lower in
Recommendations Classa Levelb the group assigned to revascularization than in the group assigned to
medical therapy. Based on this evidence, immediate coronary angiog-
Radial access is recommended as the standard
raphy, and PCI if feasible, is recommended in patients with acute MI
approach, unless there are overriding procedural I A
complicated by CS. In patients with coronary anatomy unsuitable for
considerations.451,452
PCI, emergency CABG is recommended.394
PCI with stent deployment in the IRA during the Nearly 80% of ACS patients with CS have MVD. Based on the Culprit
index procedure is recommended in patients I A Lesion Only PCI versus Multivessel PCI in Cardiogenic Shock
undergoing PPCI.490–494 (CULPRIT-SHOCK) trial including ACS patients (both with and with-
Continued out ST-segment elevation or equivalent), PCI during the index
3770 ESC Guidelines
procedure should be restricted to the IRA only.404 In the 10.2. Patients with multivessel coronary
CULPRIT-SHOCK trial, IRA-only PCI was associated with a significant
reduction in all-cause death or renal replacement therapy at 30-day
artery disease undergoing primary
follow-up (RR 0.83, 95% CI, 0.71–0.96).404 At 1-year follow-up, mortal- percutaneous coronary intervention
ity did not differ significantly between the two groups.505 Multivessel disease is evident in approximately half of patients undergo-
For patients undergoing emergency CABG, appropriate peri- ing PPCI and is associated with an adverse prognosis.506,507
operative strategies (particularly in relation to prophylactic or on- Over the past decade, a series of RCTs have provided clinical evidence
demand mechanical circulatory support) may be considered based on that supports preventive revascularization of non-IRA after successful
pre-operative clinical status (e.g. age, comorbidities, electrical instability, PPCI of the IRA. The pivotal clinical trials (in chronological order) include
the extent of jeopardized myocardium, the duration of ischaemia from PRAMI (Preventive Angioplasty in Myocardial Infarction), CvLPRIT
the time of symptom onset, right ventricular involvement, and the feasi- (Complete versus Lesion-only Primary PCI Trial), DANAMI-3–
bility of cardiac surgery from technical/logistical perspectives). Figure 14 PRIMULTI (Third Danish Study of Optimal Acute Treatment of
shows the algorithm for the management of patients with ACS and Patients with ST-Segment Elevation Myocardial Infarction—Primary

MVD. PCI in Multivessel Disease), COMPARE-ACUTE (Comparison
Patient with ACS undergoing PCI of IRA with an angiographically significant stenosis in ≥ 1 non-IRA
Cardiogenic shock STEMI NSTE-ACS
Immediate PCI of IRA only Complete revascularizationb

(Class I) Complete revascularization, (Class IIa)
either during the index
procedure or within Functional invasive
Staged complete 45 daysa evaluation of the non-IRA
revascularization (Class I) during the index procedure
(Class IIa) (Class IIb)
Figure 14 Algorithm for the management of acute coronary syndrome patients with multivessel coronary artery disease. CABG, coronary artery bypass
grafting; IRA, infarct-related artery; MVD, multivessel disease; NSTE-ACS, non-ST-elevation acute coronary syndrome; PCI, percutaneous coronary inter-
vention; STEMI, ST-elevation myocardial infarction; TIMI, Thrombolysis In Myocardial Infarction.aIn patients presenting with STEMI and MVD without CS,
complete revascularization either during the index PCI procedure or within 45 days, with PCI of non-IRA based on angiographic severity, is recommended.
b
In patients presenting with NSTE-ACS and MVD, complete revascularization, preferably during the index procedure should be considered. Functional in-
vasive evaluation of non-IRA severity during the index procedure may be considered.
ESC Guidelines 3771
Between FFR Guided Revascularization Versus Conventional Strategy in Angiography for Multivessel Evaluation) trial reported that 65% of lesions
Acute STEMI Patients With MVD), and COMPLETE (Complete vs. in the angiographic severity range of 50–70% diameter stenosis, and 20% of
Culprit-only Revascularization to Treat Multivessel Disease After Early lesions in the range 71–90%, have an FFR value above 0.80.521
PCI for STEMI) (further details on these trials is provided in the The PRIME-FFR registry included 533 ACS patients and reported that
Supplementary data online evidence tables).508–511 systematic FFR measurement led to a change in the management strategy
In a systematic review of 10 randomized trials that included 7030 pain 38% of cases (e.g. from CABG to PCI or to medical treatment), without
tients with STEMI and MVD, complete revascularization was associated an impact on MACE, death/MI, or angina symptoms at 1 year.522 A sub-
with reduced CV mortality compared with IRA-only PCI.512 All-cause group analysis of the FAME trial in 328 patients with ACS (UA or
mortality was comparable in both groups. Complete revascularization NSTEMI) and MVD reported that the adoption of FFR to guide PCI re-
was also associated with a reduced composite of CV death or new MI, sup- sulted in similar risk reductions of MACE compared with patients with
porting complete revascularization in patients with STEMI and MVD.512 stable angina, with a lower number of stents implanted and less contrast
media use.523 The FAMOUS-NSTEMI (Fractional Flow Reserve Versus
Angiographically Guided Management to Optimise Outcomes in
10.3. Timing of non-infarct-related artery

Unstable Coronary Syndromes) trial randomized 350 patients with
revascularization in acute coronary NSTE-ACS and at least one coronary stenosis (with diameter stenosis
syndrome >30%) to either angiography-guided or FFR-guided management (medical
10.3.1. Patients presenting with ST-elevation therapy, PCI, or CABG), and demonstrated that a higher proportion of
myocardial infarction and multivessel coronary patients in the FFR-guided management group were initially treated
artery disease with medical therapy. The FLOWER-MI (Flow Evaluation to Guide
The previous ESC STEMI Guidelines recommended non-IRA PCI dur- Revascularization in Multivessel ST-Elevation Myocardial Infarction) study
ing the index procedure. The primary rationale for this recommenda- randomized 1171 patients undergoing PPCI with MVD to complete re-
tion was that all trials available until then had performed MVD PCI in vascularization guided by FFR or angiography. Compared with an
that time frame. However, in the COMPLETE trial, non-IRA PCI in pa- angiography-guided approach, an FFR-guided strategy did not reduce
tients allocated to complete revascularization was performed either the risk of death, MI, or urgent revascularization at 1 year.524 PCI was per-
during hospitalization (67% of cases) or after discharge (33% of cases), formed in 66.2% of patients in the FFR-guided group and in 97.1% of the
at a mean time of 23 days after discharge but always within 45 days.511 angiography-guided group. In FLOWER-MI, complete revascularization
No treatment effect by timing of PCI interaction was observed. Given during the index procedure was only performed in 4% of patients in
that the optimal timing of revascularization (immediate vs. staged) has both groups, and functional evaluation was mainly undertaken at the
still not been investigated in adequately sized randomized trials with a time of the second procedure.524 However, based on the study design,
superiority design, no recommendation in favour of an immediate vs. complete revascularization could also be performed during a separate
a staged (i.e. either during index hospitalization or within 45 days of dis- staged procedure as early as possible before hospital discharge and within
charge) non-IRA PCI strategy can be formulated. No surgical studies 5 days of the initial procedure.
have specifically investigated non-IRA revascularization. A meta-analysis of 10 RCTs (including 3031 patients undergoing PPCI)
assessed outcomes in patients with complete revascularization vs.
IRA-only PCI according to whether the decision to carry out non-IRA
10.3.2. Patients presenting with non-ST-elevation preventive PCI was based on angiography alone or on angiography plus
acute coronary syndrome and multivessel coronary FFR.525 Preventive PCI of the non-IRA was associated with a significant
artery disease reduction in cardiac death and non-fatal MI only when the decision to
While there are a large number of studies providing evidence for patients proceed with non-IRA PCI was based solely on angiography. Similar find-
presenting with STEMI and MVD, there are fewer data guiding the man- ings were reported in another meta-analysis of seven RCTs including a
agement of patients presenting with NSTE-ACS and MVD.513 Currently, total of 6597 patients undergoing PPCI.526 In patients randomised to
there is no dedicated trial comparing complete revascularization against the complete revascularization arm, an angiography-guided strategy
IRA-only PCI for these patients. Observational studies and meta-analyses (≥70% diameter stenosis) for non-IRA lesions was associated with lower
of non-randomized studies suggest that complete revascularization is as- rates of recurrent MI, whereas an FFR-guided (≤0.80 for lesions with
sociated with fewer deaths and MACE during follow-up in comparison to ≤90% diameter stenosis) guided approach was not. In another
IRA-only PCI.514,515 However, given that these are analyses of treatment meta-analysis, which pre-dated the FLOWER-MI trial, there was no het-
effects based on non-randomized studies, the results should be consid- erogeneity in the primary outcome when complete revascularization was
ered as hypothesis-generating at best and this remains a gap in evidence. performed using an FFR-guided strategy (OR 0.78, 95% CI, 0.43–1.44) or
an angiography-guided strategy (OR 0.61, 95% CI, 0.38–0.97; P = 0.52 for
10.4. Evaluation of non-infarct-related interaction).512 A pooled post-hoc patient-level analysis of three RCTs
(FAME, DANAMI-3–PRIMULTI, and FAMOUS-NSTEMI) in ACS pa-
artery stenosis severity (angiography vs. tients treated with a functionally complete revascularization strategy
physiology) (i.e. PCI of the stenosis with FFR ≤0.80, deferral to medical therapy sten-
Overestimation of the severity of non-IRA lesions during the PPCI proced- osis with FFR >0.80) reported that the residual SYNTAX score (a proxy
ure when assessed by quantitative coronary angiography as compared of the residual coronary stenosis deferred to medical therapy) was not
with a repeated angiogram performed within 9 months has been re- associated with MACE at 2 years, suggesting that it may be safe to defer
ported.516 Microvascular constriction may also occur in the non-IRAs, the management of functionally non-significant stenoses in the
leading to some variation in functional measurements between baseline non-IRA.527 The FRAME AMI (FFR Versus Angiography-Guided
and follow-up, although the impact on decision-making may be mo- Strategy for Management of AMI With Multivessel Disease) trial com-
dest.517–520 A sub-analysis of the FAME (Fractional Flow Reserve versus pared selective PCI guided by FFR (PCI if FFR ≤0.80) to routine PCI
3772 ESC Guidelines
guided by angiography (PCI if diameter stenosis >50%) of the non-IRA(s) Multivessel disease in haemodynamically stable STEMI patients
in patients presenting with AMI who had undergone successful PCI of the undergoing PPCI
IRA (47% STEMI, 53% NSTEMI).528 This study reported that at a median
Complete revascularization is recommended either
follow-up of 3.5 years, the primary endpoint (death, MI, or repeat revas-
during the index PCI procedure or within 45 I A
cularization) occurred less frequently in patients randomized to the 508–511,531
days.
FFR-guided strategy, mainly driven by differences in patients presenting
with NSTEMI. However, the trial was terminated early, with only 562 It is recommended that PCI of the non-IRA is based
I B
out of an intended 1292 patients enrolled, and there was a relatively small on angiographic severity.511,524
number of primary outcome events. Invasive epicardial functional assessment of
non-culprit segments of the IRA is not III C
recommended during the index procedure.
10.5. Hybrid revascularization Multivessel disease in haemodynamically stable NSTE-ACS

Hybrid coronary revascularization (HCR) is defined as combined or patients undergoing PCI
consecutive procedures consisting of an internal mammary artery graft In patients presenting with NSTE-ACS and MVD,
to the left anterior descending artery (LAD) and PCI to the other complete revascularization should be considered, IIa C
non-LAD vessels for the treatment of MVD.529 The preferred surgical preferably during the index procedure.513,514
technique for HCR is a minimally invasive left anterior mini-
© ESC 2023
Functional invasive evaluation of non-IRA severity
thoracotomy or robotic-assisted left internal mammary artery
during the index procedure may be IIb B
(LIMA)-LAD. The rationale for HCR is to combine the prognostic ben-
considered.518,527,528,532
efits of a LIMA for grafting of the LAD with the potential benefits of
contemporary PCI with DES for disease in arteries that would other- ACS, acute coronary syndrome; CABG, coronary artery bypass grafting; IRA,
wise be revascularized using vein grafts (which are prone to occlu- infarct-related artery; MVD, multivessel disease; NSTE-ACS, non-ST-elevation acute
coronary syndrome; PCI, percutaneous coronary intervention; PPCI, primary
sion).530 There is limited evidence from RCTs to support hybrid percutaneous coronary intervention; STEMI, ST-elevation myocardial infarction.
revascularization. Clinical decision-making in this regard should involve a
the Heart Team. Clinical criteria supporting an HCR strategy in ACS pa-
b
Level of evidence.
c
Based on ischaemia, symptoms, patient comorbidities, and clinical condition.
tients with an indication for CABG may include MVD with LAD suitable
for CABG and non-LAD lesions suitable for PCI, atheroma in the as-
cending aorta, an unprotected left main coronary artery that is unsuit-
able for PCI, complex LAD disease, advanced age, low LVEF (≤30%),
frailty, diabetes mellitus, renal failure, prior sternotomy, and the lack
of available bypass conduits. 11. Myocardial infarction with
Recommendation Table 12 — Recommendations for non-obstructive coronary arteries
management of patients with multivessel disease Myocardial infarction with non-obstructive coronary arteries
(MINOCA) refers to the clinical situation when a patient presents
with symptoms suggestive of ACS, demonstrates troponin elevation,
It is recommended to base the revascularization and has non-obstructive coronary arteries at the time of coronary angi-
strategy (IRA PCI, multivessel PCI/CABG) on the ography (defined as coronary artery stenosis <50% in any major epicar-
patient’s clinical status and comorbidities, as well as dial vessel). The reported prevalence of MINOCA varies widely across
I B studies (from around 1% to 14% of patients with ACS undergoing angi-
their disease complexity, according to the principles
of management of myocardial ography).533 MINOCA can be considered as an umbrella term that en-
revascularization.480,481 compasses a heterogeneous group of underlying causes. This includes
both coronary and non-coronary pathologies, with the latter including
Multivessel disease in ACS patients presenting in cardiogenic
both cardiac and extra-cardiac disorders (Figure 15).4,18,534–537
shock
IRA-only PCI during the index procedure is
I B
recommended.404,505
Staged PCI of non-IRA should be considered.c IIa C
Continued

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European Heart Journal (2023) 44, 3720–3826 ESC GUIDELINES

2023 ESC Guidelines for the management

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Table of contents 3.3.2. Central laboratory vs. point of care .......................................

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CCTA Coronary computed tomography angiography ESC European Society of Cardiology

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Table 1 Classes of recommendations

Definition Wording to use

Class I Evidence and/or general agreement Is recommended or is indicated

Class II Conflicting evidence and/or a divergence of opinion about the usefulness/

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Class IIb Usefulness/efficacy is less well May be considered

Class III Evidence or general agreement that the Is not recommended

Table 2 Levels of evidence

Level of Data derived from multiple randomized clinical trials

Level of Data derived from a single randomized clinical trial

Level of Consensus of opinion of the experts and/or small studies,

ACS encompasses a spectrum

Unstable angina NSTEMI STEMI

1 Think ‘A.C.S.’ at initial assessment

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2 Think invasive management

Primary PCI Fibrinolysis Immediate angiography ± PCI Early (<24 h) angiography

3 Think antithrombotic therapy

Aspirin P2Y12 inhibitor UFH LMWH Bivalirudin Fondaparinux

PCI CABG Intravascular imaging Intravascular physiology

5 Think secondary prevention

Antithrombotic Lipid lowering Smoking Cardiac Risk factor Psychosocial

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Oligo/ Increasing chest Persistent chest Cardiogenic shock/ Cardiac

Normal ST segment ST segment Malignant

Non-elevated Rise and fall

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Clinical presentation Working diagnosisa Further investigations Final diagnosisb

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ECG ± Angiography NSTEMI

2.4. What is new

Table 4 New recommendations

Recommendations Classa Levelb

Recommendations for antiplatelet and anticoagulant therapy in acute coronary syndrome

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Table 5 Revised recommendations

Recommendations for imaging for patients with suspected NSTE-ACS

Recommendations for cardiac arrest and out-of-hospital cardiac arrest

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ECG Physical examination Clinical history Vital signs hs-cTna levels

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Immediate angiography ± Immediate angiography Consider angiography

Non-immediate Intravascular Non-invasive hs-cTna ECG

Long-term Lifestyle Smoking

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