Factors that favor the occurrence of cough in patients treated with ramipril – A pharmacoepidemiological study

Abstract

SummaryBackgroundDry cough is a common cause for the discontinuation of ramipril treatment. The aim of this pharmacoepidemiological study was to assess the incidence of ramipril-related cough among the Polish population and to characterize patients at risk of experiencing the adverse effect of cough during ramipril treatment.Material/MethodsThis was a prospective observational study involving 10,380 patients treated with ramipril for a period of no longer than 8 weeks, consisting of 3 visits: baseline, first follow-up (after 4–8 weeks) and second follow-up visit (after 4–8 weeks of cessation of ramipril, conducted only for evaluating coughing patients).ResultsThe incidence of ramipril-related cough was 7.1%. Logistic regression analysis identified female sex (OR=1.35), cigarette smoking (OR=2.50), chronic obstructive pulmonary disease (OR=1.70), asthma (OR=1.60) and previous history of tuberculosis (OR=6.20) to be significantly and independently associated with the onset of ramipril-related cough.Coughing subsided within a period of 2–20 days after ramipril was discontinued. In all patients reporting the appearance of cough within the first 5 days after therapy initiation, the adverse effect subsided after therapy discontinuation. If cough appeared within 6–10 days, it subsided after discontinuation in 81.6% of subjects. Cough persisted in 30.4% of those reporting later onset.Conclusions1. Female sex, cigarette smoking, COPD, asthma, and previous history of tuberculosis increase the risk of ramipril-related cough. 2. The later the cough occurs during treatment, the less often the drug is the causative agent and the cough and also less likely to disappear after discontinuation of ramipril.

Determinants of angiotensin‐converting enzyme inhibitor (ACEI) intolerance and angioedema in the UK Clinical Practice Research Datalink

“…Therefore, only an indirect comparison with the results of previous studies on ACEI‐induced cough is possible. While we confirmed the association with asthma, the association with COPD was in the opposite direction to that found in the above‐mentioned study . A potential explanation for this could be that ACEI users with COPD who already experience cough as a symptom of COPD might be less likely to attribute cough to ACEIs, and therefore less likely to be switched to ARBs.…”

“…A study by Wyskida et al . found that asthma and COPD were associated with ACEI‐related cough, with age‐adjusted ORs of 1.60 and 1.70, respectively . Based on validation of the database marker for ACEI intolerance used in our analyses, at least half of the cases of ACEI intolerance in the present study might be considered as having had ACEI‐related cough .…”

The impact of age and sex on the reporting of cough and angioedema with renin–angiotensin system inhibitors: a case/noncase study in VigiBase

“…Sex, age, fentanyl, methotrexate, nitrofurantoin, propofol, and drugs for obstructive airway diseases (OADs) – adrenergics (inhalants) and other OADs (inhalants) – were considered as possible risk factors for cough . For angioedema, sex, age, nonsteroidal anti‐inflammatory drugs, contrast agents, and opioids were considered as possible risk factors .…”

ACEI-induced cough: A review of current evidence and its practical implications for optimal CV risk reduction

“… 16 , 17 , 18 , 19 , 20 , 21 In fact, not all ACEI trials included cough as an endpoint, and these studies have been limited by smaller sample sizes and lack of long-term follow-up with a low number of events, which, in turn, has resulted in marked differences in reported incidences. 16 , 17 , 18 , 19 , 20 , 21 Moreover, the incidence of cough varies among individual ACEIs, and only a few ACEIs have real-world clinical practice data to support findings from randomized trials. In this context, perindopril is an ACEI for which extensive evidence from both randomized trials and real-world data are available.…”