The incidence and clinical predictors of ACE-inhibitor induced dry cough by perindopril in 27,492 patients with vascular disease

Objectives: Our objective was to investigate the actual incidence and clinical determinants of cough leading to discontinuation of ACE-inhibitors. Cough is the most frequent reason to stop ACE-inhibitor treatment. Methods: We studied 27,492 ACE-inhibitor naive patients randomized to the ACE-inhibitor perindopril or placebo using individual data of 3 clinical trials. Multivariate logistic regression analysis was used to study the incidence of cough in relation to baseline clinical characteristics including racial background. Results: In 27,492 patients with cardiovascular disease, 1076 patients discontinued ACE-inhibitor perindopril due to cough (3.9%), 703 patients during run-in period of 4 weeks and 373 patients during a mean four years of follow-up. Significant determinants of cough were female gentler (OR 1.92 95% CI 1.68-2.18), age above 65 years (OR 1.53 95% CI 1.35-1.73), and concomitant use of lipid-lowering agents (OR 1.37; 95% CI 1.181.59). A simple clinical risk score composed of these 3 predictors of cough mounted to an odds ratio of 44 (95% CI 3.1-5.4) in the subjects with highest score (i.e all determinants present). Racial background was not related to a differential incidence of cough in patients of Caucasian or Asian descendent (OR 1.1195% CI 0.92-1.39). Conclusion: This large combined analysis of randomized clinical trials in 27,492 patients showed an overall lower incidence of cough leading to discontinuation of ACE-inhibitors (3.9%) as compared to literature. CIinical determinants of such cough are older age, female gender and concomitant use of lipid-lowering agents. In contrast, racial differences were not related to the incidence of cough. (C) 2014 Elsevier Ireland Ltd. All rights reserved.