Effects of modulators of the renin???angiotensin???aldosterone system on cough

OBJECTIVE: To compare the incidence of cough in patients with a history of angiotensin converting enzyme (ACE) inhibitor-related cough who received 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, parallel-group controlled trial. SETTING: Outpatient clinics at 20 tertiary care medical centres in 11 countries. PATIENTS: One hundred and thirty-five patients with uncomplicated primary hypertension with a history of ACE inhibitor-related cough were randomly assigned to the double-blind treatment phase and completed the study. INTERVENTION: After confirming that the cough was ACE inhibitor-related by a single-blind rechallenge, followed by a placebo washout period, patients were randomly assigned to receive 50mg losartan, 20mg lisinopril or 25mg hydrochlorothiazide once a day for 8 weeks. MAIN OUTCOME MEASURES: Cough incidence, severity and frequency were assessed by a self-administered questionnaire and a visual analogue scale. RESULTS: The percentage of patients who complained of cough was significantly higher with lisinopril than with losartan or hydrochlorothiazide. The mean visual analogue scale scores for patients treated with lisinopril demonstrated that these patients coughed more frequently than those who received losartan or hydrochlorothiazide. CONCLUSION: The incidence of cough related to the type 1 Ang II receptor antagonist losartan is significantly lower than that observed with lisinopril, and similar to that observed with hydrochlorothiazide in patients with a rechallenged ACE inhibitor cough. Type 1 Ang II receptor antagonists represent a potential new treatment for hypertensive patients in whom ACE inhibitors are indicated, but who develop a cough with these agents.