What is the clinical evidence from this study?

Study design: Meta-Analysis. Population: Cardiovascular disease (n=65054). Intervention: Angiotensin-converting enzyme inhibitors (ACE-I) vs. Placebo. Primary outcome: Incident coughing.

January 13, 2018

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

Key Result

Angiotensin-converting enzyme inhibitors were associated with a 13.5% rate of cough versus 8.5% on placebo, indicating that 63% of cough cases on ACE inhibitors may be due to other factors.

Study Design

Type

Meta-Analysis (n=65,054)

Randomization

Randomized

Structured PICO

Does Angiotensin-converting enzyme inhibitors (ACE-I) increase cough in patients with cardiovascular disease?

Population

65,054 patients with cardiovascular disease from 22 randomized, placebo-controlled trials evaluating cough on ACE inhibitors.

Intervention

Angiotensin-converting enzyme inhibitors (ACE-I)

Comparator

Placebo

Outcome

Rate of cough (attributable fraction of cough on ACE-I accounting for rate on placebo)safety

A substantial proportion of cough cases in patients taking ACE inhibitors may be due to other factors, particularly in heart failure, suggesting other causes should be excluded before withdrawing ACE-I therapy.

Main Result

Absolute Event Rate: 13.5% vs 8.5%

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 (%) = (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.

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Cite This Study

Vukadinović et al. (Sat,) conducted a meta-analysis in Cardiovascular disease (n=65,054). Angiotensin-converting enzyme inhibitors (ACE-I) vs. Placebo was evaluated on Incident coughing. Angiotensin-converting enzyme inhibitors were associated with a 13.5% rate of cough versus 8.5% on placebo, indicating that 63% of cough cases on ACE inhibitors may be due to other factors.

synapsesocial.com/papers/6a20f1fa34bef10fdaeb2aab https://doi.org/https://doi.org/10.1002/cpt.1018

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