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Differential properties of mibefradil in hypertension and angina.

Abstract
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.
AuthorsI Kobrin
JournalJournal of hypertension. Supplement : official journal of the International Society of Hypertension (J Hypertens Suppl) Vol. 15 Issue 5 Pg. S33-40 (Dec 1997) ISSN: 0952-1178 [Print] England
PMID9481614 (Publication Type: Clinical Trial, Comparative Study, Journal Article, Randomized Controlled Trial)
Chemical References
  • Benzimidazoles
  • Calcium Channel Blockers
  • Tetrahydronaphthalenes
  • Mibefradil
  • Diltiazem
  • Nifedipine
Topics
  • Angina Pectoris (drug therapy)
  • Benzimidazoles (adverse effects, therapeutic use)
  • Calcium Channel Blockers (therapeutic use)
  • Diltiazem (therapeutic use)
  • Double-Blind Method
  • Heart Rate (drug effects)
  • Humans
  • Hypertension (drug therapy)
  • Mibefradil
  • Nifedipine (therapeutic use)
  • Tetrahydronaphthalenes (adverse effects, therapeutic use)

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