Antihypertensive monotherapy with tablet (prompt-release) diltiazem: multicenter controlled trials

The tablet formulation of diltiazem has been available for the treatment of angina pectoris but has not been comprehensively evaluated in hypertension. This study's aim was to evaluate the efficacy, dose-response characteristics, and duration of action of tablet (prompt-release) diltiazem in mild to moderate hypertension. Three placebo-controlled trials were designed. The first (trial #1) evaluated the dose response of 120, 240, and 360 mg/day (q12h regimen) of diltiazem in parallel fixed-dose fashion using hourly blood pressures. The second (trial #2) evaluated a q12h titration from 240 to 360 mg/day, which could be switched to q8h. The third (trial #3) evaluated a q8h titration from 180 to 270 to 360 mg/day, followed by conversion to a q12h regimen. The goal was a supine diastolic blood pressure of less than 90 mmHg and 10 mmHg less than baseline. With doses of diltiazem increasing from 120 to 240 to 360 mg/day, there was a progressive decrease in the average mean arterial pressure, describing a dose response with 120 mg/day as the ineffective dose. The peak effect for each dose regimen was found at 6 hours, with significant reductions lasting over 10 hours in the 240 mg/day and 360 mg/day groups. Peak plasma concentrations occurred at 3 hours. The residual effect at the trough of the 240 mg/day and 360 mg/day doses was 48% and 53% of the peak effect, respectively. When titration was carried out on a q8h regimen, both systolic and diastolic blood pressures were significantly decreased. When the regimen was switched from q8h to q12h, the effect was not maintained.(ABSTRACT TRUNCATED AT 250 WORDS)