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 diuretic to diltiazem at apparent optimum doses of each agent significantly enhances their antihypertensive effects. DESIGN: Multicenter, randomized, 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 from 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 Hg or less after 4-6 weeks in the baseline phase. Of the patients enrolled, 298 met the inclusion criteria. INTERVENTIONS: Combination therapy with DTZ SR-HCTZ 120 mg-12.5 mg, or monotherapy with DTZ SR 120 mg or HCTZ 12.5 mg, or placebo was administered twice daily. MEASUREMENTS AND MAIN RESULTS: Combination therapy with DTZ SR-HCTZ lowered both supine DBP and SBP significantly (p < 0.005) more than either single agent. The combination also lowered DBP and SBP significantly more than either monotherapy. During a 12-hour in-clinic monitoring period spanning a dosing interval, both the combination and DTZ SR therapies maintained efficacy, whereas the antihypertensive effects of HCTZ dissipated after 8 hours. Treatment-related adverse events for the combination and HCTZ were similar but slightly greater than those for DTZ SR and placebo. CONCLUSIONS: The addition of a diuretic to sustained-release diltiazem produced an enhanced antihypertensive effect compared with monotherapy with either individual agent.
RCT Entities:
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 diuretic to diltiazem at apparent optimum doses of each agent significantly enhances their antihypertensive effects. DESIGN: Multicenter, randomized, 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 from 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 Hg or less after 4-6 weeks in the baseline phase. Of the patients enrolled, 298 met the inclusion criteria. INTERVENTIONS: Combination therapy with DTZ SR-HCTZ 120 mg-12.5 mg, or monotherapy with DTZ SR 120 mg or HCTZ 12.5 mg, or placebo was administered twice daily. MEASUREMENTS AND MAIN RESULTS: Combination therapy with DTZ SR-HCTZ lowered both supine DBP and SBP significantly (p < 0.005) more than either single agent. The combination also lowered DBP and SBP significantly more than either monotherapy. During a 12-hour in-clinic monitoring period spanning a dosing interval, both the combination and DTZ SR therapies maintained efficacy, whereas the antihypertensive effects of HCTZ dissipated after 8 hours. Treatment-related adverse events for the combination and HCTZ were similar but slightly greater than those for DTZ SR and placebo. CONCLUSIONS: The addition of a diuretic to sustained-release diltiazem produced an enhanced antihypertensive effect compared with monotherapy with either individual agent.