Once-daily fixed combination of captopril and hydrochlorothiazide as first line therapy for mild to moderate hypertension

The efficacy and safety of a single daily dose of captopril combined with hydrochlorothiazide were evaluated in a double-blind, placebo-controlled, randomized, multicenter, parallel-group study. Three-hundred forty-five patients with mild to moderate hypertension (seated diastolic blood pressure [DBP], 92 to 109 mmHg) were randomly assigned to receive placebo, 25 mg of captopril, 12.5 mg of hydrochlorothiazide, 25 mg of captopril plus 12.5 mg of hydrochlorothiazide, or 50 mg of captopril plus 25 mg of hydrochlorothiazide. After a 4- to 6-week single-blind placebo lead-in, patients took medication once daily for 8 weeks. Blood pressure was measured 24 ± 3 hours after the last drug dose. Both combination regimens reduced seated DBP more than placebo, captopril, or hydrochlorothiazide (P < 0.05); the effects of the two combination regimens were similar. Neither 25 mg of captopril nor 12.5 mg of hydrochlorothiazide reduced seated DBP more than placebo. After 8 weeks, both combinations normalized seated DBP (≤90 mmHg) in approximately 60% of patients, which exceeded the 35% normalization rate in the placebo group (P < 0.05). The frequency of clinical adverse events was similar (approximately 40%) in the placebo group and the two combination groups. It is concluded that both combinations of captopril and hydrochlorothiazide studied are suitable for once-daily treatment of mild to moderate hypertension, but the lower dose is preferred as initial therapy.