Antianginal and anti-ischemic effects of mibefradil in the treatment of patients with chronic stable angina pectoris

Joseph S. Alpert, Ad L.M. Bakx, Shimon Braun, William H. Frishman, Adam Schneeweiss, Dan Tzivoni, Isaac Kobrin

Research output: Contribution to journalArticle

8 Scopus citations

Abstract

Five placebo-controlled, double-blind, multicenter, parallel-design studies were performed to evaluate the antianginal and anti-ischemic characteristics of the novel T-channel-selective calcium antagonist, mibefradil, in the treatment of patients with chronic stable angina pectoris. Of the 5 studies, 2 were monotherapy dose-finding trials and 3 were conducted in patients receiving background antionginal therapy: either β blockers (2 studies) or long-acting nitrates (1 study). A total of 865 patients were randomized to 1 of 4 mibefradil dose groups (25, 50, 100, and 150 mg; n = 565) and placebo (n = 300). The antianginal and anti-ischemic effects of mibefradil were assessed across all 5 studies by evaluating exercise tolerance test variables, weekly number of anginal attacks and short-acting nitroglycerin consumption, and in both dose-finding studies, the number and total duration of silent ischemic episodes (48-hour Holter monitoring). A statistically significant increase in exercise duration was achieved in 3 of 5 studies with the 50-mg dose of mibefradil and in 3 of 3 studies with the 1.00-mg dose of the compound over the effects observed in the placebo groups. A significant delay in time to onset of ischemia during exercise was induced in all studies with the 50- and 100-mg doses of mibefradil. The 25-mg dose of mibefradil was not significantly better than placebo, and the effects of the 150-mg close of the compound were similar to those observed with the 100-mg dose. Across all studies, a dose-related decrease was observed in the number of weekly anginal attacks and in weekly nitroglycerin consumption. Similarly, a significant dose-related decrease in the number and duration of silent ischemic episodes was observed during Holter monitoring for 48 hours in the 2 dose-finding studies. The antianginal and antiischemic effects were associated with a dose-related decrease in heart rate and double product both at rest and at exercise termination. Treatment with the 50- and 100-mg doses of mibefradil was found to be well tolerated and safe compared with placebo, a finding that held true for patients on chronic β-blocker or long-acting nitrate therapy. Taken together, these studies indicate that mibefradil is an effective and well-tolerated once daily treatment for chronic stable angina pectoris at doses of 50 and 100 mg, which are the lowest and highest effective doses of the compound, respectively.

Original languageEnglish (US)
Pages (from-to)20C-26C
JournalAmerican Journal of Cardiology
Volume80
Issue number4 B
DOIs
StatePublished - Aug 21 1997

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine

Fingerprint Dive into the research topics of 'Antianginal and anti-ischemic effects of mibefradil in the treatment of patients with chronic stable angina pectoris'. Together they form a unique fingerprint.

  • Cite this