A dose escalation trial comparing the combination of diltiazem SR and hydrochlorothiazide with the monotherapies in patients with essential hypertension

Abstract

A multicentre, randomised, placebo-controlled parallel group study comparing various doses of the combination diltiazem SR (DTZ SR)/hydrochlorothiazide (HCTZ) with the monotherapies was performed to delineate the optimal antihypertensive dosage of the two drug combinations. The study was carried out in 298 patients with mild to moderate essential hypertension (stable supine diastolic blood pressure, DBP, greater than or equal to 95 and less than or equal to 110 mmHg). After a single-blind placebo lead-in period lasting 4-6 weeks to establish stable baseline BP, the patients were randomised to receive either placebo (n = 75), HCTZ (n = 76), DTZ SR (n = 72), or the combination of DTZ SR/HCTZ (n = 75). There were three 4-week evaluation periods with forced escalation of therapy as follows: HCTZ (6.25, 6.25, 12.5 mg twice daily), DTZ SR (60, 90, 120 mg twice daily), and the combination of DTZ SR/HCTZ (60/6.25, 90/6.25, 120/12.5 mg twice daily). DTZ SR/HCTZ (120/12.5 mg) produced statistically significantly greater reductions in supine DBP compared with each monotherapy and placebo. The lower doses of DTZ SR/HCTZ (60/6.25 mg and 90/6.25 mg) produced statistically significantly greater supine DBP reductions compared with DTZ SR monotherapy and placebo, but not compared with HCTZ monotherapy. A comparison of reduction in supine DBP between evaluation periods demonstrated a dose-response relationship for the combination therapy in reducing BP over the dosage range studied. Adverse clinical and laboratory events were not significantly different between the therapies.(ABSTRACT TRUNCATED AT 250 WORDS)