title: The incidence and clinical predictors of ACE-inhibitor induced dry cough by perindopril in 27,492 patients with vascular disease.
abstract: OBJECTIVE
  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).
  
  
  CONCLUSIONS
  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.affiliation: Department of Cardiology, Erasmus University Medical Center, Thoraxcenter, Rotterdam, The Netherlands. Electronic address: j.brugts@erasmusmc.nl.
authors.forename: J J
authors.initials: JJ
authors.lastname: Brugts
authors.affiliation: 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.
authors.forename: Hisatomi
authors.initials: H
authors.lastname: Arima
authors.affiliation: STICARES Cardiovascular Research Institute, Rhoon, The Netherlands.
authors.forename: W
authors.initials: W
authors.lastname: Remme
authors.affiliation: Lille Heart Institute, Lille, France.
authors.forename: M
authors.initials: M
authors.lastname: Bertrand
authors.affiliation: Department of Cardiology, University of Ferrara, Salvatore Maugeri Foundation, IRCCS, Ferrara, Italy.
authors.forename: R
authors.initials: R
authors.lastname: Ferrari
authors.affiliation: NHLI, Imperial College, ICMS, Royal Brompton Hospital, London, United Kingdom.
authors.forename: K
authors.initials: K
authors.lastname: Fox
authors.affiliation: Mid-America Heart Institute, Saint Luke's Hospital, KS City, MO, USA.
authors.forename: J
authors.initials: J
authors.lastname: DiNicolantonio
authors.affiliation: 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.
authors.forename: S
authors.initials: S
authors.lastname: MacMahon
authors.affiliation: 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.
authors.forename: J
authors.initials: J
authors.lastname: Chalmers
authors.affiliation: Department of Cardiology, Erasmus University Medical Center, Thoraxcenter, Rotterdam, The Netherlands.
authors.forename: F
authors.initials: F
authors.lastname: Zijlstra
authors.affiliation: Department of Cardiology, Erasmus University Medical Center, Thoraxcenter, Rotterdam, The Netherlands.
authors.forename: K
authors.initials: K
authors.lastname: Caliskan
authors.affiliation: Department of Cardiology, Erasmus University Medical Center, Thoraxcenter, Rotterdam, The Netherlands.
authors.forename: M L
authors.initials: ML
authors.lastname: Simoons
authors.affiliation: Department of Internal Medicine and Arterial Hypertension, CHJ Avicenne, APHP, Bobigny, France.
authors.forename: J J
authors.initials: JJ
authors.lastname: Mourad
authors.affiliation: Department of Cardiology, Erasmus University Medical Center, Thoraxcenter, Rotterdam, The Netherlands.
authors.forename: E
authors.initials: E
authors.lastname: Boersma
authors.affiliation: Department of Cardiology, Erasmus University Medical Center, Thoraxcenter, Rotterdam, The Netherlands.
authors.forename: K M
authors.initials: KM
authors.lastname: Akkerhuis
mesh_terms: D000367:Age Factors; D000368:Aged; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000009:adverse effects*; D003371:Cough / Q000139:chemically induced* / Q000175:diagnosis / Q000453:epidemiology*; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D015994:Incidence; D008297:Male; D008875:Middle Aged; D020913:Perindopril / Q000009:adverse effects*; D011237:Predictive Value of Tests; D012737:Sex Factors; D014652:Vascular Diseases / Q000188:drug therapy* / Q000453:epidemiology*
chemical_list: D000806:Angiotensin-Converting Enzyme Inhibitors; D020913:Perindopril
keywords: ACE-inhibitor; Cough; Intolerance; Perindopril