ANTIANGINAL AND ANTIISCHEMIC EFFECTS OF MIBEFRADIL, A NEW T-TYPE CALCIUM-CHANNEL ANTAGONIST

Mibefradil is the first of a new class of calcium antagonists (CAs), t he tetralol derivatives, that selectively blocks the T-type calcium ch annel. The anti-anginal and anti-ischemic efficacy of mibefradil in pa tients with chronic stable angina pectoris was established in five pla cebo-controlled trials (2 monotherapy trials, 3 trials with background beta-blocker or long-acting nitrate therapy). At the recommended dose s of 50 and 100 mg, mibefradil treatment was associated with a signifi cant dose-related increase in exercise test variables regardless of de mographic 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 t rials compared mibefradil 100 mg with amlodipine 10 mg or diltiazem SR 120 mg b.i.d., respectively. Patients receiving mibefradil showed sig nificantly larger improvements than did those treated with amlodipine and similar improvements as those treated with diltiazem SR in all var iables measured. In both studies, treatment with mibefradil was associ ated with a greater decrease in HR and rate-pressure product. Mibefrad il was found to be well tolerated and safe; this held true for patient s on chronic anti-anginal background therapy. The overall incidences o f adverse events and premature withdrawals were only slightly higher t han those of placebo-treated patients. Asymptomatic sinus bradycardia and first-degree atrioventricular block were the most frequently occur ring mibefradil dose-related ECG changes. Mibefradil was better tolera ted than amlodipine (mainly with regard to leg edema) and similarly we ll tolerated as diltiazem CD.