Mibefradil is the first of a new class of
calcium antagonists (CAs), the
tetralol derivatives, that selectively blocks the
T-type calcium channel. The anti-anginal and anti-ischemic efficacy of
mibefradil in patients with
chronic stable angina pectoris was established in five placebo-controlled trials (2 monotherapy trials, 3 trials with background beta-blocker or long-acting
nitrate therapy). At the recommended doses of 50 and 100 mg,
mibefradil treatment was associated with a significant dose-related increase in exercise test variables regardless of demographic subpopulation or background
therapy. Significant reductions in weekly anginal attacks, silent ischemic parameters, heart rate (HR) and rate-pressure product were also observed. Two active-controlled trials compared
mibefradil 100 mg with
amlodipine 10 mg or
diltiazem SR 120 mg b.i.d., respectively. Patients receiving
mibefradil showed significantly larger improvements than did those treated with
amlodipine and similar improvements as those treated with
diltiazem SR in all variables measured. In both studies, treatment with
mibefradil was associated with a greater decrease in HR and rate-pressure product.
Mibefradil was found to be well tolerated and safe; this held true for patients on chronic anti-anginal background
therapy. The overall incidences of adverse events and premature withdrawals were only slightly higher than those of placebo-treated patients. Asymptomatic sinus
bradycardia and first-degree
atrioventricular block were the most frequently occurring
mibefradil dose-related ECG changes.
Mibefradil was better tolerated than
amlodipine (mainly with regard to leg
edema) and similarly well tolerated as
diltiazem CD.