J J Brugts1, Hisatomi Arima2, W Remme3, M Bertrand4, R Ferrari5, K Fox6, J DiNicolantonio7, S MacMahon2, J Chalmers2, F Zijlstra8, K Caliskan8, M L Simoons8, J J Mourad9, E Boersma8, K M Akkerhuis8. 1. Department of Cardiology, Erasmus University Medical Center, Thoraxcenter, Rotterdam, The Netherlands. Electronic address: j.brugts@erasmusmc.nl. 2. The George Institute for Global Health, The Royal Prince Alfred Hospital, Sydney, NSW, Australia; The George Institute for Global Health, The University of Sydney, Sydney, NSW, Australia. 3. STICARES Cardiovascular Research Institute, Rhoon, The Netherlands. 4. Lille Heart Institute, Lille, France. 5. Department of Cardiology, University of Ferrara, Salvatore Maugeri Foundation, IRCCS, Ferrara, Italy. 6. NHLI, Imperial College, ICMS, Royal Brompton Hospital, London, United Kingdom. 7. Mid-America Heart Institute, Saint Luke's Hospital, KS City, MO, USA. 8. Department of Cardiology, Erasmus University Medical Center, Thoraxcenter, Rotterdam, The Netherlands. 9. Department of Internal Medicine and Arterial Hypertension, CHJ Avicenne, APHP, Bobigny, France.
Abstract
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 naïve 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 gender (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 1.18-1.59). A simple clinical risk score composed of these 3 predictors of cough mounted to an odds ratio of 4.4 (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 1.11 95% 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. Clinical 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.
RCT Entities:
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 naïve 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 gender (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 1.18-1.59). A simple clinical risk score composed of these 3 predictors of cough mounted to an odds ratio of 4.4 (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 1.11 95% 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. Clinical 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.
Authors: Lorcan McGarvey; Bruce K Rubin; Satoru Ebihara; Karen Hegland; Alycia Rivet; Richard S Irwin; Donald C Bolser; Anne B Chang; Peter G Gibson; Stuart B Mazzone Journal: Chest Date: 2021-04-24 Impact factor: 10.262
Authors: Sungmin Lim; Eun Ho Choo; Ik Jun Choi; Sang Hyun Ihm; Hee Yeol Kim; Youngkeun Ahn; Kiyuk Chang; Myung Ho Jeong; Ki Bae Seung Journal: J Korean Med Sci Date: 2019-11-25 Impact factor: 2.153
Authors: J J Brugts; M Bertrand; W Remme; R Ferrari; K Fox; S MacMahon; J Chalmers; M L Simoons; E Boersma Journal: Cardiovasc Drugs Ther Date: 2017-08 Impact factor: 3.727