Safety update: focus on cough.

Abstract

Overall, angiotensin-converting enzyme (ACE) inhibitors have a very low side-effect profile. However, several reports in the literature cite cough as a possible complication of ACE inhibitor therapy. These reports have prompted speculation that the risk of cough may differ among ACE inhibitors and that the risk may be greater in patients with renal impairment, perhaps because of excessive drug accumulation. However, these hypotheses have not been tested in prospective, controlled studies. Fosinopril is a long-acting ACE inhibitor with a unique chemical structure and an elimination profile that is associated with stable clearance, regardless of the degree of renal impairment. Favorable clinical experience with fosinopril led to the evaluation of this agent's cough profile in a prospective, open-label study. This study focused on the frequency of cough in patients with mild-to-moderate hypertension who had previously experienced cough while taking another ACE inhibitor. Whereas most prior controlled studies and postmarketing surveillance trials measured the frequency of cough through spontaneous adverse-event reporting, in this study a methodology previously validated in antitussive and mucolytic studies was adapted to provide accurate and sensitive measure of fosinopril's cough profile. Twenty-four patients were switched from another ACE inhibitor to fosinopril, 10 mg once daily for 6 weeks. At study end, the mean occurrence of cough, frequency of cough, and cough severity significantly changed from baseline (p < or = 0.0002). Thus, fosinopril use was associated with a less frequent, less severe cough in patients who experienced cough while taking other ACE inhibitors.