A randomized, double-masked comparison of the antihypertensive efficacy and safety of combination therapy with losartan and hydrochlorothiazide versus captopril and hydrochlorothiazide in elderly and younger patients

Abstract

A multinational, randomized trial was conducted to compare the antihypertensive efficacy and safety of the combination therapy of the angiotensin II receptor antagonist losartan with hydrochlorothiazide (HCTZ) (fixed-dose tablet) with that of the angiotensin-converting enzyme inhibitor captopril with HCTZ (fixed-dose tablet) in elderly and younger patients with mild-to-moderate essential hypertension. The study consisted of a 4-week single-masked placebo baseline period followed by a 12-week double-masked, parallel comparison of once-daily administration of losartan 50 mg/HCTZ 12.5 mg or captopril 50 mg/HCTZ 25 mg (2:1 randomization ratio). Patients with a mean trough sitting diastolic blood pressure (SiDBP) of 95 to 115 mm Hg after the placebo baseline period were randomly assigned to receive losartan/HCTZ (n = 216) or captopril/HCTZ (n = 109). At each center, patients were stratified according to age (<65 and ⩾65 years). The primary efficacy variable was the mean change from baseline to week 12 in trough SiDBP. Safety was assessed by recording adverse experiences and clinical laboratory measurements. At week 12, mean reductions from baseline in trough sitting systolic blood pressure and SiDBP were comparable in the losartan/HCTZ (21.5 and 12.6 mm Hg, respectively) and captopril/HCTZ (20.6 and 13.4 mm Hg, respectively) groups. Both fixed-dose combinations had an equal response regardless of the age of the patient. At week 12, a similar percentage of patients in the losartan/HCTZ and captopril/HCTZ groups had a trough SiDBP less than 90 mm Hg or a 10 mm Hg or greater reduction from baseline (71% and 75%, respectively). Significantly fewer patients in the losartan/HCTZ group had clinical adverse experiences that were considered drug related by the investigator (9% vs 18%). The incidences of cough and headache also were much less in the losartan/HCTZ group. Captopril/HCTZ was associated with significantly greater mean elevations in serum creatinine and uric acid and mean decreases in serum potassium. We concluded that once-daily administration of losartan 50 mg and HCTZ 12.5 mg as a fixed-dose tablet is an effective regimen for both elderly and younger patients with mild-to-moderate essential hypertension. The antihypertensive efficacy of the losartan 50 mg/HCTZ 12.5 mg combination is comparable to that of the captopril 50 mg/HCTZ 25 mg combination, but losartan/HCTZ has a more favorable safety, tolerability, and metabolic profile.