DOSE-RESPONSE CHARACTERISTICS OF MIBEFRADIL, A NOVEL CALCIUM-ANTAGONIST, IN THE TREATMENT OF ESSENTIAL-HYPERTENSION

The aim of this study was to determine the dose-response characteristi cs of the calcium antagonist, mibefradil, and to evaluate its antihype rtensive efficacy and safety in varying doses in patients with mild-to -moderate hypertension. Three hundred and three eligible patients were randomized to receive once-daily 6.25-, 12.5-, 25-, 50-, 100-, 150-, or 200-mg mibefradil doses or placebo for 4 weeks. Repeated blood pres sure measurements and electrocardiographic recordings were obtained fo r the 24 h following the last dose of the placebo run-in period and fo r the first and last doses of randomized treatment. A statistically si gnificant (P < .001 versus placebo) and clinically relevant drop in si tting diastolic blood pressure (SDBP) both at trough and at peak was o bserved in the 50-, 100-, 150-, and 200-mg mibefradil dose groups (tro ugh placebo-corrected reductions: -4.9, -9.1, -9.9, and -11.9 mm Hg, r espectively), with a significant dose-response relationship (P < .001) and high response rates. Trough/peak ratios for the placebo-corrected change from baseline to week 4 in SDBP were >85% for the 50- and 100- mg doses and 68% and 69% far the 150- and 200-mg doses, respectively. The full antihypertensive effect of mibefradil was achieved within 1 w eek of treatment. Reductions in sitting systolic blood pressure (SSBP) closely paralleled those in SDBP. The antihypertensive effect of mibe fradil was associated with a slight dose-dependent decrease in heart r ate and increase in the pulse rate (PR) interval. The appropriate ther apeutic dose range of mibefradil in the management of mild-to-moderate essential hypertension is 50 to 100 mg. (C) 1997 American Journal of Hypertension, Ltd.