Rate of Cough During Treatment With Angiotensin‐Converting Enzyme Inhibitors: A Meta‐Analysis of Randomized Placebo‐Controlled Trials

Abstract

Use of protective angiotensin‐converting enzyme inhibitors (ACE‐I) in patients with cardiovascular disease (CVD) is sometimes limited by incident coughing. In clinical trials, cough occurred also on placebo. We performed a meta‐analysis including randomized, placebo‐controlled trials reporting cough on ACE‐I in patients with CVD. We evaluated the attributable fraction of cough on ACE‐I accounting rate on placebo: placebo‐adjusted ACE‐I (%)\u2009=\u2009(ACE‐I (%) – Placebo (%)) / ACE‐I (%). In total, 65,054 patients from 22 included studies were analyzed. Placebo‐adjusted ACE‐I cough was 37% of 13.5% reported cases on ACE‐I, while 8.5% reported cases on placebo were equivalent to 63% of cases on ACE‐I, indicating potential other factors for cough than ACE‐I in a substantial number of cough cases on ACE‐I. Placebo‐adjusted ACE‐I cough had the highest rates of arterial hypertension (85%) and the lowest of heart failure (29%). Therefore, other causes of cough, particularly in heart failure, should be excluded before ACE‐I withdrawal.