Effects of benazepril and hydrochlorothiazide, given alone and in low- and high-dose combinations, on blood pressure in patients with hypertension
S. G. Chrysant, T. Fagan, R. Glazer and A. Kriegman
Oklahoma Cardiovascular and Hypertension Center, University of Oklahoma, Oklahoma City, USA.
OBJECTIVE: To assess the efficacy and safety of several combinations of
benazepril, an angiotensin-converting enzyme inhibitor, and
hydrochlorothiazide, as compared with placebo, in the treatment of patients
with essential hypertension. DESIGN: A 6-week, randomized, double-blind,
parallel study conducted at 24 centers. A placebo run-in period of 1 to 4
weeks preceded the double-blind phase. PARTICIPANTS AND SETTING: Male and
female outpatients, aged 18 years and older, were eligible to participate
if their sitting diastolic blood pressure was between 95 and 114 mm Hg at
the last two consecutive visits during the placebo phase. Among the 334
patients who entered the double-blind phase, 17% were aged 65 years or
older and 26% were black. Eleven patients withdrew because of adverse
experiences, including two patients receiving placebo. INTERVENTIONS:
Patients received placebo; benazepril, 20 mg; hydrochlorothiazide, 25 mg;
or combination therapy with benazepril/hydrochlorothiazide, 5/6.25 mg,
10/12.5 mg, 20/25 mg, 20/6.25 mg, or 5/25 mg, once daily for 6 weeks. MAIN
OUTCOME MEASURES: The mean change from baseline in sitting diastolic blood
pressure at end point (last postrandomization measurement carried forward)
in the double-blind phase. Combination therapy with
benazepril/hydrochlorothiazide, 20/25 mg, was compared with benazepril, 20
mg alone, and hydrochlorothiazide, 25 mg alone. Sitting systolic blood
pressure and the effect of race and age on treatment efficacy were also
evaluated. RESULTS: Compared with placebo, all
benazepril/hydrochlorothiazide combinations produced statistically
significant reductions from baseline in sitting diastolic and systolic
blood pressures at study end point. In the benazepril/hydrochlorothiazide,
20/25 mg, group, the adjusted mean changes in sitting diastolic blood
pressure at end point were statistically significantly greater than those
in the monotherapy treatment groups (benazepril, 20 mg, P < or = .05;
hydrochlorothiazide, 25 mg, P < or = .001) alone. All therapies were
generally well tolerated. Decreases in mean serum potassium level with
hydrochlorothiazide monotherapy were reduced or eliminated with combination
therapy. CONCLUSION: Benazepril in combination with hydrochlorothiazide,
including a low-dose combination of 5/6.25 mg, is effective in reducing
sitting diastolic and systolic blood pressure in patients with
hypertension.
