EFFECTS OF MODULATORS OF THE RENIN-ANGIOTENSIN-ALDOSTERONE SYSTEM ON COUGH

Objective: To compare the incidence of cough in patients with a histor y of angiotensin converting enzyme (ACE) inhibitor-related cough who r eceived losartan [a type 1 angiotensin II (Ang II) receptor antagonist ], lisinopril (an ACE inhibitor) or hydrochlorothiazide (a diuretic). Design: An international, multicentre, randomized, double-blind, paral lel-group controlled trial. Setting: Outpatient clinics at 20 tertiary care medical centres in 11 countries. Patients: One hundred and thirt y-five patients with uncomplicated primary hypertension with a history of ACE inhibitor-related cough were randomly assigned to the double-b lind treatment phase and completed the study. Intervention: After conf irming that the cough was ACE inhibitor-related by a single-blind rech allenge, followed by a placebo washout period, patients were randomly assigned to receive 50 mg losartan, 20 mg lisinopril or 25 mg hydrochl orothiazide once a day for 8 weeks. Main outcome measures: Cough incid ence, severity and frequency were assessed by a self-administered ques tionnaire and a visual analogue scale. Results: The percentage of pati ents who complained of cough was significantly higher with lisinopril than with losartan or hydrochlorothiazide. The mean visual analogue sc ale scores for patients treated with lisinopril demonstrated that thes e patients coughed more frequently than those who received losartan or hydrochlorothiazide. Conclusion: The incidence of cough related to th e type 1 Ang II receptor antagonist losartan is significantly lower th an that observed with lisinopril, and similar to that observed with hy drochlorothiazide in patients with a rechallenged ACE inhibitor cough. Type 1 Ang II receptor antagonists represent a potential new treatmen t for hypertensive patients in whom ACE inhibitors are indicated, but who develop a cough with these agents.