MIBEFRADIL IN THE TREATMENT OF
HYPERTENSION: The
antihypertensive efficacy of
mibefradil, a new selective transient (T)-channel
calcium antagonist, was studied in eight randomized, double-blind, parallel-design trials: four placebo-controlled and four active
drug-controlled versus other
calcium antagonists. These studies established that at doses of 50 and 100 mg,
mibefradil is an effective, well tolerated and safe treatment for
high blood pressure. The
antihypertensive effect of
mibefradil was achieved gradually, with the full activity reached within 1-2 weeks. The decrease in arterial pressure was smooth and sustained over the entire 24-h dosing interval. The
antihypertensive action was associated with a dose-related reduction in the heart rate. The efficacy results were similar across all demographic subpopulations studied, including high-risk groups: individuals with
chronic renal failure; the elderly; and
hydrochlorothiazide-treated patients. In studies comparing
mibefradil with other
calcium antagonists at their recommended doses, 100 mg
mibefradil demonstrated significantly better
antihypertensive efficacy than controlled-dose (CD)
diltiazem at 360 mg or slow release (SR)
nifedipine at 40 mg twice a day, and similar efficacy to that of 10 mg
amlodipine or 60 mg
nifedipine gastrointestinal therapeutic system (GITS).
MIBEFRADIL IN THE TREATMENT OF
ANGINA PECTORIS: The efficacy, safety, and tolerability of 50 and 100 mg
mibefradil in the treatment of
chronic stable angina pectoris was tested in six randomized parallel-design studies. Significant increases in exercise duration and a significant delay in the onset of
ischemia during exercise were found in most studies with the 50-mg dose and in all studies with the 100-mg dose. Weekly anginal attacks and nitroglycerine consumption decreased significantly in a dose-related manner and, similarly, a significant dose-related decrease in the number and duration of silent ischemic episodes was observed on 48-h Holter monitoring. In the two studies with active drug controls, 100 mg
mibefradil was significantly better than 10 mg
amlodipine and equivalent to 120 mg
diltiazem SR twice a day in improving anti-anginal and anti-ischemic parameters. In all studies,
mibefradil treatment produced a dose-related reduction in the heart rate and the rate-pressure product at rest and at the end of exercise, and the magnitude of these decreases was larger than that observed with the other two
calcium antagonists. SAFETY AND TOLERABILITY: An integrated analysis of combined data on the safety and tolerability of
mibefradil from studies on
hypertension and
angina pectoris confirmed that
mibefradil and
diltiazem were equally well tolerated, but the incidence of leg
edema was clearly higher in patients treated with the
dihydropyridine calcium antagonists
amlodipine and
nifedipine.