Heart Failure Pharmacy
Heart Failure Pharmacy
Heart Failure Pharmacy
MANAGING HEART
FAILURE
Dr Vincent Chan
Discipline of Pharmacy
School of Health and Biomedical Sciences
RMIT University
Email: vincent.chan@rmit.edu.au
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Lecture Overview
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Learning Objectives
After this lecture, you should be able to:
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Heart Failure: Impact
• Affects about 2% of Australian and incidence & prevalence
increase with age
➢ ~1% in people aged 50-59; >50% in people aged 85
• More females than males die of heart failure because they
generally live longer (males higher if age-standardised)
• High mortality rate (although falling)
➢ In Australia: ~61,000 HF related deaths/yr
➢ Mild heart failure → ~50% mortality at 5 years
➢ Severe heart failure → ~50% mortality at 1 year
• High hospitalisation and readmission rates → Major cost!!
• Major disease burden because of high cost of care (expected
to ), symptomatic, low quality of life and premature death
• National Heart Foundation
• Australian Institute of Health and Welfare 2012. Australia’s health 2012; Chen et al. 2017 5
Heart Failure Classification
• New York Heart Association (NYHA) Classes
Class Definition Terminology
Marked limitations to
III Moderate heart failure
physical activity
This leads to
• FLUID RETENTION To maintain
• VASOCONSTRICTION perfusion, body
• INCREASED VENOUS compensates
RETURN • Renin/Angiotensin/Aldost
• INCREASED FORCE of erone
CONTRACTION • Sympathetic drive
• INCREASED RATE OF (including centrally)
CONTRACTION • + others
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Vicious Cycle / Tightrope
• Setting off this cycle leads to an acute worsening in the
condition
– Acute exacerbation of HF
– Patient becomes worse over hours – weeks
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Classification of HF
• Two ways:
diminished
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HF: 1) Classification by SIDE
• Predominantly LEFT vs RIGHT sided
• Right sided:
– Hepatic congestion
– Peripheral oedema
– Elevated venous pressure
• Left sided
– Pulmonary congestion
– Shortness of breath
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HF: 2) Classification by Ejection Fraction
• Usually: HF is a disease of systolic dysfunction due to myocardial
damage
– Leading to decreased left ventricular ejection fraction (majority)
– “Left Ventricular Systolic Dysfunction Heart Failure” (LVSD-HF)
– “HF with reduced left ventricular ejection fraction” (HFrEF)
– 2D imaging of heart
– Can show you thickening, ejection fraction etc.
• Blood test:
– Brain Natriuretic Peptide
– Secreted by ventricles when they are overstretched
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Heart Failure - management
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HF Pathophysiology: Targets for
Pharmacotherapy?
Heart is damaged &
cannot output
effectively to body
This leads to
• FLUID RETENTION To maintain
• VASOCONSTRICTION perfusion, body
• INCREASED VENOUS compensates
RETURN • Renin/Angiotensin/Aldost
• INCREASED FORCE of erone
CONTRACTION • Sympathetic drive
• INCREASED RATE OF (including centrally)
CONTRACTION • + others
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Heart Failure - management
Aim to:
• Improve symptoms
• Improve exercise tolerance
• Reverse disease progression & deterioration in
ventricular function
• Reduce hospital admissions
• Live longer (reduce mortality)
Add diuretic
+ other Inotropes??
• Aldosterone antagonists
• Digoxin
Improve symptoms
• Diuretics only
• Inotropes
+ non-pharmacological measures
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Medicines for Reduced Ejection Fraction HF
• ACE-inhibitors
– Probably the front-runner/clear winner
• Should be started ASAP after diagnosis of HF
• Evidence & recommended for all grades of HF
• Class effect – variation in duration of action
• Improves symptoms, prognosis, hospitalizations and
deaths
• In all patients with HFrEF, for all classes of the disease,
at all times
• The higher the dose of the ACE-I, the better the patient
does
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Medicines for Reduced Ejection Fraction HF
• Dosing:
– Start low, go slow
– titrate up dose every 2 weeks to maximally
tolerated dose
– Do not want to drop patient’s BP too suddenly
– Monitor: GFR and electrolytes (K+ especially)
– Can tolerate a small decrease in GFR, BP or a small
rise in K+
– HF patients are more likely to get these problems,
as they have worsened physiological capacity to
tolerate ‘insults’ to the system
• Symptomatic improvements may not be seen for weeks-
months after initiation of an ACE inhibitor
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Angiotensin Receptor Blockers (sartans/ATRAs)
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What if patient cannot have ACE-I OR ARB?
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Medicines for Reduced Ejection Fraction HF
• Beta-Blockers
– Used to be contraindicated….now standard Tx!
– Belief was: decreasing force of contraction would make
heart failure worse
– There is now unequivocal evidence that in patients with HF,
beta-blockers:
– Decrease mortality
– Decrease hospitalisations
– Improve symptoms
– However….. Caution is required!
• Not a class effect
• Evidence: combined -blocker/ACEI is better than ACEI alone
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Beta blockers for HF
• Recommendation:
– Add a Beta blocker to ACE-I therapy
– For patients with HF
– With STABLE disease without recent exacerbations
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Beta blockers in HF – Dosing Strategy
• ABSOLUTELY
CRITICAL to start low
and go slow
• Like ACE-I, aim for
target doses as high as
possible
o BUT DO NOT be
overly aggressive • Taken from NPS News 75 – Systolic Heart Failure: Improving
Treatment
signs of worsening HF
• Dose increase every 2-
4 weeks if patient stable
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Beta Blockers in HF
• Which beta-blockers to use?
– Not all have evidence (some no improvement, some
worst)
– Only four currently have evidence:
▪ Metoprolol Slow/Extended Release
– (Normal release metoprolol is commonly used for
HT & for other things, but effectiveness in HF ??)
▪ Carvedilol (also an alpha blocker)
▪ Bisoprolol
▪ Nebivolol (newest of the four – thus least evidence)
– All PBS-Restricted
• Benefits not immediately apparent (Persevere!! -
Symptomatic improvements may not be seen for months)
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Carvedilol
• Non-specific
– 1-blocker What might you expect with
– 1-blocker the additional 1-blockade??
– 2-blocker
– “Antioxidant” effects
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Medicines for Reduced Ejection Fraction HF
• Aldosterone antagonists
• eg. Spironolactone & Eplerenone
• Improve symptoms and mortality when added to 1st
line therapy in patients with ongoing symptoms
• Add in to patients who still have symptoms on ACE-I & β-
blocker
• Significant risks: Hyperkalaemia!!
– eg. ACE-I + K+-sparing diuretic in combination
• EVIDENCE: Significant benefit in decreasing
hospitalisations, mortality and morbidity
• Eplerenone is PBS-A (HF after acute MI)
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Aldosterone antagonists
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Three other drugs for HF….
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Newer Drug…. (“ARNI”)
• Entresto®
• Combines the moieties of an ARB (valsartan) and a
neprilysin inhibitor (sacubitril)
• New ACE inhibitor alternative; PBS-A listed mid 2017
– More effective than enalapril [PARADIGM-HF trial]
– Better for kidneys
• Evidence currently insufficient to recommend as first-line
• Seems to have similar risks and adverse effects as ACE
inhibitors (probably less)
– Hypotension, hyperkalaemia and angiodema
• Need to cease ACEI or sartan before commencing
• Valsartan dose in this fixed dose combo NOT equivalent
to valsartan dose in other products
• Keep watching this space!!
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Ivabradine
• Coralan® ; PBS-A for HF only
• Inhibits cardiac pacemaker (If) current to HR
• SHIFT trial showed decreased HF hospitalisation and CV
death
• Added to therapy if HR remains high despite maximal
beta-blocker therapy, and:
– Patient must have sinus rhythm and a resting heart rate 77 bpm
at the time ivabradine treatment is initiated
– Patient must receive concomitant optimal standard chronic heart
failure treatment, which must include the maximum tolerated dose
of a beta-blocker, unless contraindicated or not tolerated
• Aldosterone antagonists
• Digoxin
Improve symptoms
• Diuretics only
• Inotropes
+ non-pharmacological measures
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Symptomatic Management - Diuretics
• In HF diuretics are used to remove fluid
• They are for symptomatic relief (oedema)
• Loop diuretics are most effective diuretics (eg. Furosemide)
• Not used as monotherapy but combined with standard
therapy
• High doses are sometimes needed (eg. renal impairment)
• Patients with severe acute HF may require intravenous
diuretics
• Monitor: Creatinine – will probably worsen renal function
(can tolerate a bit of worsening)
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Loop diuretics – patient counselling/issues
• Produce rapid & intense diuresis (Onset within 1 hour (oral);
4-6 hour duration of action)
• Take in the morning – can keep patients up at night going to
toilet
– BD doses often given at 0800 and 1200 for this reason
• In practice:
– STOP thiazides if patient commences loop diuretic
– Occasionally combo used intentionally with difficult to treat
oedema
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Digoxin
• Digoxin’s actions are:
– POSITIVE inotrope
– Increase FORCE of contraction
– NEGATIVE chronotrope
– Decrease RATE of contraction
– Decrease sympathetic tone?
• By injection
• Dobutamine IV infusion is most common
• These will increase the force of contraction, and improve
symptoms in the short term
• In the long term, will shorten the lifespan of the heart
• Hence, use is for:
– End of life symptomatic management
– Short term use in patients who are severely ill or awaiting transplant
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Heart Failure: Contraindicated drugs
• NSAIDs (including COX-2 selective)
• Will cause constriction of afferent arteriole in
kidney
– Decrease perfusion to kidney
– Fluid retention, RAAS activation, hypertension etc.
etc. etc.
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Heart Failure: Contraindicated drugs
• Verapamil or Diltiazem
• These will depress cardiac contractility (like
beta-blockers)
– Therefore they can worsen heart failure
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