Ace Inhibitors : Comparison of Ace Inhibitors (Perindopril, Ramipril & Lisinopril) Induced Cough
Ace Inhibitors : Comparison of Ace Inhibitors (Perindopril, Ramipril & Lisinopril) Induced Cough
Ace Inhibitors : Comparison of Ace Inhibitors (Perindopril, Ramipril & Lisinopril) Induced Cough
ACE INHIBITORS;
COMPARISON OF ACE INHIBITORS (PERINDOPRIL, RAMIPRIL &
LISINOPRIL) INDUCED COUGH.
amirnazir234@yahoo.com
Dr. Amar Nazir1, Dr. Fida Muhammad Sheikh2, Dr. Shahzad Aslam3,Dr. Uzma Javaid4
1. FCPS
Assistant Professor Medicine ABSTRACT: Persistent dry cough is commonest undesirable effect of the angiotensin converting
Sargodha Medical College enzyme inhibitors. The mechanism of cough due to ACE inhibitors is uncertain, but most likely
2. FCPS
is due to the cough mediators as substance P agents & brdykinin which are degraded by
Assistant Professor Cardiology
Sargodha Medical College ACE inhibitors. Objective: To compare the incidence of cough in hypertensives which were
3. FCPS prescribed lisinopril, perindopril & ramipril. Study Design: Mainly cross sectional prospective
Assistant Professor Cardiology multicenter, open labeled study of 100 patients. Place & Duration of Study: Department of
Sargodha Medical College
4. MBBS Medicine of University Medical Diagnostic Centre & District Head Quarter Hospital Sargodha,
Lecturer period January 2016 to June 2016. Methodology: 100 Patients using three types of ACE
Sargodha Medical College inhibitors were selected and an especially designed performa was completed. In our study we
gave preference to those patients who were prescribed ACE inhibitors for the first time. The
Correspondence Address:
Dr. Amar Nazir patients were instructed (at the baseline visit) to inform during the succeeding visit about the
FCPS onset of any adverse drug reactions like cough, hypotension, headache, dizziness, fatigue,
Assistant Professor Medicine nausea, angioedema. Patients were not informed that incidence of cough was the main seek of
Sargodha Medical College
amirnazir234@yahoo.com the study, so there was no chance for Hawthorne effect. Results: The incidence of ACE inhibitor
induced cough has been reported to as: perindopril was 5.4 %, ramipril 6.89 % & lisinopril 8.82
Article received on: %. Overall incidence of dry cough was 7.0 % with three different ACE inhibitors. The onset
22/06/2016
of cough after taking ACE inhibitors ranges from within days of the first dose to months after
Accepted for publication:
17/08/2016 starting the therapy. Cough usually resolves within 1 to 4 weeks after the cessation of treatment.
Received after proof reading: Conclusion: Chronic dry cough is a general consequence of angiotensin converting enzyme
10/09/2016 inhibitors. The cough is also associated with irritating & tickling sensations in throat.
Article Citation: Nazir A, Sheikh FM, Aslam S, Javaid U. Ace Inhibitors; Comparison of ace
inhibitors (perindopril, ramipril & lisinopril) induced cough. Professional Med
J 2016;23(9):1145-1148. DOI: 10.17957/TPMJ/16.3501
INTRODUCTION proved their efficacy in treating complicated
The first angiotensin converting enzyme inhibitor situations such as CCF in diabetics with
was introduced in 1981. In treatment of different hypertension patients.3 In 1985 Sesko & Kanehoy
diseases affecting the quality of life (congestive first described ACE inhibitors induced cough in
cardiac failure, hypertension, ventricular Annals Internal Medicine.4 Even as the benefits of
dysfunction, acute coronary syndrome and ACE inhibitors are documented, coughing is their
diabetic nephropathy), ACE inhibitors have commonest side effect, occasionally entailing
brought an innovative change and their affectivity cessation of therapy.5 Cough can start even within
in endothelial problems have also been proved. In a week of starting the medication.6 Other side
patients having co morbidities like hypertension effects which influence the quality of life due to
with diabetes, the use of ACE inhibitors prevent cough have included sore throat, vomiting, voice
the worsening of renal activity and reduces changes, sleep disturbance and urinary stress
albuminuria.1 incontinence in type II diabetics.7 According to
post marketing surveys which were carried out in
ACE inhibitors act as vasodilators and 1980s, the incidence of ACE inhibitors induced
reduce peripheral vascular resistance to treat cough was 0% to 12% but Zafar Israeli & Hall
hypertension.2 These anti hypertensive’s in reviewed the literature & reported the incidence
combination with diuretics and digoxin have to range from 0.7% to 48% in their medical trials.8
Professional Med J 2016;23(9): 1145-1148. www.theprofesional.com 1145
ACE INHIBITORS 2
of treatment. Generally cough resolves within a observational time period the dry cough was
week after termination of medication, but it may reported only in 3.0% of patients. To evaluate
persist for as 4-5 weeks.6,12 our results, we selected 29 patients taking
ramipril, the percentage of cough Incidence was
During current clinical trial a self-administered 6.89 % which was relatively high as compare to
complaint evaluation survey was carried out at CARE study. The results were not comparable
every visit to calculate the cough incidence. The and this incidence of CARE study might have
evaluation Performa for this study was tailored underestimated due to short time span of only
from assessment questionnaires of previous few weeks.15
mucolytic and antitussive surveys. Estimation
of symptoms occurring in these hypertensive Our results regarding Lisinopril also are
patients gave a precise gauge of ACE inhibitors comparable to one study which showed a high
related cough. rate of withdrawal of ACE inhibitor therapy due
to raised incidence of cough among black as
Outcome of this study sustain the premise that compare to nonblack patients (9.5% : 2.3%).
arid grating cough is a well-known effect caused Lisinopril induced undesirable effects were noted
by ACE inhibitors. These results are relatively as, cough most frequent (1.5 % - 10%), raised level
analogous to one study conducted in Ireland of creatinine (7%) and rihinitis (up to 1%). Other
by Brugett’s-JJ & Arima-H in which patients very unusual effects were eosinophilic pulmonary
were clinically judged for perindopril induced disease, bronchospasm, rhino sinusitis and
cough by using multivariate logistic regression fibrosing alveolitis.16
analysis. Randomized clinical trials were done in
27,492 patients and analysis of results revealed The outcomes of our study support the hypothesis
a low incidence of cough (about 4%). This type that all ACE inhibitors can cause dry annoying
of cough has strong association with advanced and troublesome cough.
age, female gender & simultaneous use of statins.
However, cough incidence was not related to CONCLUSION
ethnic differences.13 ACE inhibitors should be considered as entirely
or partly causative, In a patient with persistent
Regarding ramipril our study results also resemble cough. Patients suffering from congestive cardiac
with one study conducted by Katarzyna Wyskida failure, diabetic nephropathy and hypertension
& Edyta jura – Szoltys in 2010. In this study the are being treated with ACE inhibitors which
enrolled number of patients taking ramipril was usually have a low incidence of adverse effects
10,380. Among these 50.8% were males and and are exceedingly well tolerated.
49.2% females. A total of 869 patients (8.3%)
presented with the complain of dry cough in their On the whole frequency of cough due to
routine visits and it occurred usualy 14±8 days ACE inhibitors was 8% in this study which is a
(from 1 to 8 weeks) following ramipril therapy.14 bothersome consequence of these medicines
but it is tolerable as compare to those serious
One big population based study done by Kaplan- side effects which occur with other alternative anti
NM is the CARE study. The aim of study was to hypertensive agents. Therefore if the cough is not
verify the security and effectiveness of ramipril inconvenient then the use of ACE inhibitors may
and to get the outcomes of clinical trials. The be carried on. So it is very important for treating
initial dose of ramipril was 2.5mg once daily and physician to diagnose if it is ACE inhibitor induced
was titrated to gain normal blood oressure. In cough otherwise patient may be considered to
this study huge number (11,100) of American undergo expensive and needless assessments,
hypertensive patients were assessed for ramipril investigations and consultations. The subsequent
induced adverse effects and during 8 weeks of use of antibacterials, bronchodilators,
theophylline, anticholenergics and cough 9. Gianpaolo Reboldi, Giorgio Gentile Choice of ACE
suppressants may add the cost of treatment. So inhibitor combinations in hypertensive patients with
type 2 diabetes: update after recent clinical trials
the end of therapy is the only evenly effective cure Vasc. Health Risk Manag. 2009; 5: 411 – 427.
for cough due to ACE inhibitors.
Copyright© 17 Aug, 2016. 10. Lain c, Macdougall The role of ACE inhibitors and
angiotensin II receptor blockers in the response to
epoetin: Nephrology Dialysis Transplantation 1999:
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