Double‐Blind Comparison of Losartan, Lisinopril, and Metolazone in Elderly Hypertensive Patients with Previous Angiotensin‐Converting Enzyme Inhibitor‐Induced Cough

Abstract
This study compared the incidence of cough with the angiotensin‐converting enzyme (ACE) inhibitor lisinopril and the diuretic metolazone with the angiotensin II receptor antagonist losartan in elderly hypertensive patients with previous histories of ACE inhibitor‐induced cough. A randomized, double‐blind, stratified, parallel‐group comparison of lisinopril at 10 mg, losartan at 50 mg, and metolazone at 1 mg, each given once daily for a maximum of 10 weeks, was performed in four hypertension clinics in four centers in two countries. Cough was detected by a questionnaire (the primary end point) given to elderly patients with hypertension, and the cough frequency was quantified by a visual analog scale (a secondary end point). A total of 84 elderly patients with hypertension, all who were nonsmokers with ACE inhibitor‐induced cough and were confirmed by lisinopril rechallenge then placebo dechallenge, were randomized to the three treatment groups. The incidence of cough with losartan (18%) was significantly lower than with lisinopril (97%) and similar to that for metolazone (21%). Cough frequency evaluated by the visual analog scale was significantly lower for losartan than for lisinopril and similar to that for metolazone. The specific, selective angiotensin II receptor antagonist losartan is associated with a decrease in the incidence of cough in patients with previous ACE inhibitor‐induced cough.