TY - JOUR AU - Brugts J. AU - Akkerhuis K. AU - Remme W. AU - Fox K. AU - Ferrari R. AU - Zijlstra F. AU - Boersma E. AU - Bertrand M. AU - Simoons M. AU - Arima Hisatomi AU - DiNicolantonio J. AU - Caliskan K. AU - Mourad J. AU - Chalmers J. AU - Macmahon S AB -

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 4weeks 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 65years (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.

AD - Department of Cardiology, Erasmus University Medical Center, Thoraxcenter, Rotterdam, The Netherlands. Electronic address: j.brugts@erasmusmc.nl.
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.
STICARES Cardiovascular Research Institute, Rhoon, The Netherlands.
Lille Heart Institute, Lille, France.
Department of Cardiology, University of Ferrara, Salvatore Maugeri Foundation, IRCCS, Ferrara, Italy.
NHLI, Imperial College, ICMS, Royal Brompton Hospital, London, United Kingdom.
Mid-America Heart Institute, Saint Luke's Hospital, KS City, MO, USA.
Department of Cardiology, Erasmus University Medical Center, Thoraxcenter, Rotterdam, The Netherlands.
Department of Internal Medicine and Arterial Hypertension, CHJ Avicenne, APHP, Bobigny, France. AN - 25189490 BT - International Journal of Cardiology DP - NLM ET - 2014/09/06 [epub ahead of print] IS - 3 LA - Eng LB - UK
PDO
NMH N1 - Brugts, J J
Arima, Hisatomi
Remme, W
Bertrand, M
Ferrari, R
Fox, K
DiNicolantonio, J
MacMahon, S
Chalmers, J
Zijlstra, F
Caliskan, K
Simoons, M L
Mourad, J J
Boersma, E
Akkerhuis, K M
Int J Cardiol. 2014 Aug 1. pii: S0167-5273(14)01318-7. doi: 10.1016/j.ijcard.2014.07.108. N2 -

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 4weeks 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 65years (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.

PY - 2014 SN - 1874-1754 (Electronic)
0167-5273 (Linking) SP - 718 EP - 23 T2 - International Journal of Cardiology TI - The incidence and clinical predictors of ACE-inhibitor induced dry cough by perindopril in 27,492 patients with vascular disease VL - 176 ER -