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

A multinational, randomized trial was conducted to compare the antihyp ertensive efficacy and safety of the combination therapy of the angiot ensin II receptor antagonist losartan with hydrochlorothiazide (HCTZ) (fixed-dose tablet) with that of the angiotensin-converting enzyme inh ibitor captopril with HCTZ (fixed-dose tablet) in elderly and younger patients with mild-to-moderate essential hypertension, The study consi sted of a 4-week single-masked placebo baseline period followed by a 1 2-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 ran domization 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 captopri l/HCTZ (n = 109), At each center, patients were stratified according t o age (<65 and greater than or equal to 65 years), The primary efficac y variable was the mean change from baseline to week 12 in trough SiDB P. Safety was assessed by recording adverse experiences and clinical l aboratory measurements. At week 12, mean reductions from baseline in t rough 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 combinatio ns had an equal response regardless of the age of the patient, At week 12, a similar percentage of patients in the losartan/HCTZ and captopr il/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). Significa ntly fewer patients in the losartan/HCTZ group had clinical adverse ex periences 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 de creases in serum potassium. We concluded that once-daily administratio n of losartan 50 mg and HCTZ 12.5 mg as a fixed-dose tablet is an effe ctive regimen for both elderly and younger patients with mild-to-moder ate essential hypertension. The antihypertensive efficacy of the losar tan 50 mg/HCTZ 12.5 mg combination is comparable to that of the captop ril 50 mg/HCTZ 25 mg combination, but losartan/HCTZ has a more favorab le safety, tolerability, and metabolic profile.