Cough due to ace inhibitors: a case-control study using automated general practice data

Abstract

Abstract. 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 GR 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.

Identifying Existing Evidence to Potentially Develop a Machine Learning Diagnostic Algorithm for Cough in Primary Care Settings: Scoping Review

“…Although incident coughing was associated with ACE inhibitor use (OR 2.1, 95% CI 1.5-3.1), the adjusted results were not significant. Among the individual agents, only enalapril provided statistically significant results, both unadjusted (OR 2.6, 95% CI 1.6-4.2) and adjusted (OR 1.7, 95% CI 1.03-2.8), whereas the results for captopril, lisinopril, and perindopril were not statistically significant [60].…”

“…The included articles (for summarized results related to cough, refer to Multimedia Appendix 3 ) covered the following diagnoses: COPD, asthma, obstructive airway disease (OAD), influenza or influenza-like illness, respiratory tract infection (RTI), bronchial carcinoma (BC), community-acquired pneumonia, COVID-19, dyspepsia, gastroesophageal reflux disease (GERD), differential diagnosis of pulmonary embolism, heart failure, and adverse effects of angiotensin-converting enzyme (ACE) inhibitors. Of these studies, 10 were prospective studies (Vandevoorde et al [27], Freeman et al [30], Price et al [34], Eysink et al [38], Kable et al [39], Navarro-Marí et al [44], Thursky et al [45], Senn et al [46], Govaert et al [26], and Hollenz et al [59]), 8 were prospective cohort or diagnostic studies (Hamers et al [29], Schneider et al [37], Pescatore et al [40], Buffels et al [42], Schneider et al [53], Hippisley-Cox et al [54], Erkens et al [57], and Wallander et al [58]), 5 were cross-sectional studies (van Schayck et al [33], Melbye et al [36], Schneider et al [43], Kool et al [49], Hopstaken et al [52]), 4 were case-control studies (Haroon et al [35], Hamilton et al [55], Iyen-Omofoman et al [56], and Visser et al [60]), 2 were multicenter studies (Vrijhoef et al [32] and van Elden et al [47]), and 1 each was a descriptive (Thiadens et al [41]), retrospective (Nakanishi et al [51]), cohort (Geijer et al [28]), prospective case series (Bloom et al [50]), prospective, systematic sampling study (Sočan et al [48]) and comparative study (van Schayck et al…”

“…Nevertheless, the small number of results requires confirmation by further studies. Among ACE inhibitors, only enalapril was shown to be statistically significantly associated with incident cough [60]. However, this refers to only 1 study and therefore does not allow a reliable statement.…”

Drugs that may injure the respiratory system

“…As an example, angiotensin-converting enzyme (ACE) inhibitors may induce cough [38], β-blockers may induce bronchospasm [35], nonsteroidal anti-inflammatory drugs may induce bronchospasm or eosinophilic pneumonia [39], and ergoline drugs may induce chronic pleural thickening or effusion [40].…”