MIBEFRADIL - A NEW T-CHANNEL SELECTIVE CALCIUM-ANTAGONIST

Mibefradil is a pharmacologically distinct calcium antagonist (CA) tha t selectively blocks T-type calcium ion channels. The results from 4 p lacebo-controlled studies demonstrated that mibefradil at recommended doses is effective in the treatment of essential hypertension, inducin g a gradual and sustained decrease in both diastolic and systolic bloo d pressure without a first-dose effect, regardless of age. The overall response rate was high, and treatment was associated with a slight po tentially beneficial reduction in heart rate. In 4 active-controlled s tudies in which mibefradil was compared to other commonly used CAs for the treatment of hypertension, mibefradil was shown to be more effect ive than diltiazem CD or nifedipine SR and similar in efficacy to amlo dipine or nifedipine GITS. The findings of 5 placebo-controlled studie s indicated that mibefradil at recommended doses is an effective antia nginal and antiischemic drug given either as monotherapy or in combina tion with chronic beta-blocker therapy. Moreover, mibefradil's lack of negative inotropic effect observed in preclinical and initial clinica l studies, along with its ability to decrease cardiac workload and myo cardial oxygen demand, might prove to be especially useful in patients with impaired cardiac function. This hypothesis is currently being ev aluated in patients with congestive heart failure (1). In a comparativ e trial against amlodipine in patients with chronic stable angina pect oris, mibefradil treatment resulted in significantly larger improvemen ts in exercise performance. Similarly, larger decreases in weekly angi nal episodes and in 48-hour silent ischemia burden were observed in pa tients treated with mibefradil compared with those treated with amlodi pine. Mibefradil and diltiazem SR were found to be equally effective i n improving exercise performance and anginal diary parameters. The ext ensive safety and tolerability data collected from patients treated wi th mibefradil 50 and 100 mg confirmed that the drug is safe and very w ell tolerated. Overall, mibefradil treatment was associated with lower incidences of leg edema than amlodipine or the extended release formu lations of nifedipine and was as well tolerated as diltiazem SR/CD.