COUGH DUE TO ACE-INHIBITORS - A CASE-CONTROL STUDY USING AUTOMATED GENERAL-PRACTICE DATA

Objectives: To determine the risk of coughing as an adverse reaction t o ACE inhibitors under everyday circumstances in a large population, a nd 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 consult ations, morbidity and medical interventions, including drugs prescribe d, were registered over the 18 month period from 1st September, 1992 t o 1st March, 1994. Subjects: 1458 patients with incident coughing and up to four controls per case were obtained (total 4182 controls), matc hed for GP. All cases and controls were 20 years or older and had no r ecord of respiratory infection, influenza, tuberculosis, asthma, chron ic bronchitis, emphysema, congestive heart failure, sinusitis, laryngi tis, haemoptysis or respiratory neoplasms during the study period. Res ults: Cases were 2.1-times more likely than controls to have been expo sed 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 lisi nopril 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 lis inopril 1.7 (95% CI 0.4-7.9). For patients who had been on ACE inhibit or treatment for no longer than 2 months the odds ratio was 4.8 (95% C I 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 s everal confounding factors. The risk of developing cough due to ACE-in hibitors declines with the duration of treatment, possibly due to depl etion of susceptible persons.