Angiotensin-converting enzyme inhibitor associated cough: deceptive information from the Physicians' Desk Reference

Abstract

Background: Dry cough is a common, annoying adverse effect of all angiotensin-converting enzyme (ACE) inhibitors. The present study was designed to compare the rate of coughs reported in the literature with reported rates in the Physicians' Desk Reference (PDR)/drug label.

Methods: We searched MEDLINE/EMBASE/CENTRAL for articles published from 1990 to the present about randomized clinical trials (RCTs) of ACE inhibitors with a sample size of at least 100 patients in the ACE inhibitors arm with follow-up for at least 3 months and reporting the incidence or withdrawal rates due to cough. Baseline characteristics, cohort enrolled, metrics used to assess cough, incidence, and withdrawal rates due to cough were abstracted.

Results: One hundred twenty-five studies that satisfied our inclusion criteria enrolled 198,130 patients. The pooled weighted incidence of cough for enalapril was 11.48% (95% confidence interval [CI], 9.54% to 13.41%), which was ninefold greater compared to the reported rate in the PDR/drug label (1.3%). The pooled weighted withdrawal rate due to cough for enalapril was 2.57% (95% CI, 2.40-2.74), which was 31-fold greater compared to the reported rate in the PDR/drug label (0.1%). The incidence of cough has increased progressively over the last 2 decades with accumulating data, but it has been reported consistently several-fold less in the PDR compared to the RCTs. The results were similar for most other ACE inhibitors.

Conclusion: The incidence of ACE inhibitor-associated cough and the withdrawal rate (the more objective metric) due to cough is significantly greater in the literature than reported in the PDR/drug label and is likely to be even greater in the real world when compared with the data from RCTs. There exists a gap between the data available from the literature and that which is presented to the consumers (prescribing physicians and patients).