A RANDOMIZED, CONTROLLED TRIAL COMPARING DILTIAZEM, HYDROCHLOROTHIAZIDE, AND THEIR COMBINATION IN THE THERAPY OF ESSENTIAL-HYPERTENSION

Study Objectives. To compare the efficacy of combination therapy with sustained-release diltiazem and hydrochlorothiazide (DTZ SR-HCTZ) with that of monotherapy with DTZ SR, HCTZ, or placebo in the treatment of essential hypertension; and to determine whether the addition of a di uretic to diltiazem at apparent optimum doses of each agent significan tly enhances their antihypertensive effects. Design. Multicenter, rand omized, double-blind, placebo-controlled, parallel-group trial with a 6-week treatment phase. Setting. Private and university-based clinics. Patients and Participants. Subjects of either sex, ranging in age fro m 18-70 years, with a diagnosis of stable essential hypertension made from two consecutive weekly mean supine diastolic blood pressure (DBP) readings of 95 mm Hg or above to 110 mm Hg or less that varied 7 mm H g or less after 4-6 weeks in the baseline phase. Of the patients enrol led, 298 met the inclusion criteria. Interventions. Combination therap y with DTZ SR-HCTZ 120 mg-12.5 mg, or monotherapy with DTZ SR 120 mg o r HCTZ 12.5 mg, or placebo-was administered twice daily. Measurements and Main Results. Combination therapy with DTZ SR-HCTZ lowered both su pine DBP and SBP significantly (p<0.005) more than either single agent . The combination also lowered DBP and SBP significantly more than eit her monotherapy. During a 12-hour in-clinic monitoring period spanning a dosing interval, both the combination and DTZ SR therapies maintain ed efficacy, whereas the antihypertensive effects of HCTZ dissipated a fter 8 hours. Treatment-related adverse events for the combination and HCTZ were similar but slightly greater than those for DTZ SR and plac ebo. Conclusions. The addition of a diuretic to sustained-release dilt iazem produced an enhanced antihypertensive effect compared with monot herapy with either individual agent.