Objectives: To determine the risk of coughing as an adverse reaction to ACE inhibitors under everyday circumstances in a large population, and to study whether this adverse effect was duration or dose dependent. Design: A population-based case-control study. Setting: Ten general practices of 14 Dutch general practitioners (GP), in which all consultations, morbidity and medical interventions, including drugs prescribed, were registered over the 18 month period from 1st September, 1992 to 1st March, 1994. Subjects: 1458 patients with incident coughing and up to four controls per case were obtained (total 4182 controls), matched for GP. All cases and controls were 20 years or older and had no record of respiratory infection, influenza, tuberculosis, asthma, chronic bronchitis, emphysema, congestive heart failure, sinusitis, laryngitis, haemoptysis or respiratory neoplasms during the study period. Results: Cases were 2.1-times more likely than controls to have been exposed to ACE inhibitors (95% CI 1.5-3.1), but after adjustment the odds ratio was 1.4 (95% CI 0.9-2.1). The crude odds ratio for captopril was 1.3 (95% CI 0.7-2.5), for enalapril 2.6 (95% CI 1.6-4.2) and for lisinopril 2.0 (95% CI 0.5-9.3). The adjusted odds ratio for captopril was 0.9 (95% CI 0.4-1.7), for enalapril 1.7 (95% CI 1.03-2.8) and for lisinopril 1.7 (95% CI 0.4-7.9). For patients who had been on ACE inhibitor treatment for no longer than 2 months the odds ratio was 4.8 (95% CI 1.7-13.3). The odds ratio declined to 2.0 (95% CI 1.1-3.8) for those who had taken an ACE inhibitor for 2-6 months, and to 1.6 (95% CI 0.9-2.7) for those on ACE-inhibitors for more than 6 months. Conclusion: The risk of coughing was increased twofold among ACE inhibitor users, but the odds ratios were no longer significant after controlling for several confounding factors. The risk of developing cough due to ACE-inhibitors declines with the duration of treatment, possibly due to depletion of susceptible persons.

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doi.org/10.1007/s002280050047, hdl.handle.net/1765/62002
European Journal of Clinical Pharmacology
Department of Medical Informatics

Visser, L.E, Vlug, A.E, van der Lei, J, & Stricker, B.H.Ch. (1996). Cough due to ace inhibitors: A case control study using automated general practice data. European Journal of Clinical Pharmacology, 49(6), 439–444. doi:10.1007/s002280050047