Effects of the new calcium antagonist mibefradil (Ro 40-5967) on exercise duration in patients with chronic stable angina pectoris: a multicenter, placebo-controlled study. Ro 40-5967 International Study Group.
Mibefradil (Ro 40-5967) is a novel calcium antagonist from a new chemical class and is the first that selectively blocks the T-type calcium channel. In this multicenter, double-blind, placebo-controlled, parallel designed study, its antianginal and antiischemic effects were evaluated in 126 patients with chronic stable angina pectoris. Exercise tests were performed after 1 week of placebo (baseline) and 2 weeks after randomization to 25, 50, 100, and 150 mg (once daily) or placebo. Highly significant dose-response relations were present across all treatment groups for exercise duration, time to angina, and time to ST-segment depression. They were associated with a dose-dependent decrease in heart rate and blood pressure and plasma concentrations > 300 ng/ml. Mibefradil was well tolerated. First-degree atrioventricular block (8%) and dizziness (7%) were the most frequently reported adverse events; however, the first-degree atrioventricular block was dose-related, and only one patient discontinued the trial because of dizziness. The excellent efficacy and adequate safety profile of mibefradil may be a consequence of T-type calcium-channel selectivity.
Bakx
A L
AL
Department of Cardiology, University Hospital Leiden, The Netherlands.
van der Wall
E E
EE
Braun
S
S
Emanuelsson
H
H
Bruschke
A V
AV
Kobrin
I
I
D000328:Adult; D000368:Aged; D000787:Angina Pectoris / Q000188:drug therapy*; D001562:Benzimidazoles / Q000008:administration & dosage / Q000097:blood / Q000627:therapeutic use*; D001794:Blood Pressure; D002121:Calcium Channel Blockers / Q000008:administration & dosage / Q000097:blood / Q000627:therapeutic use*; D002908:Chronic Disease; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D005080:Exercise Test; D005260:Female; D006339:Heart Rate; D006801:Humans; D008297:Male; D020748:Mibefradil; D008875:Middle Aged; D010919:Placebos; D013764:Tetrahydronaphthalenes / Q000008:administration & dosage / Q000097:blood / Q000627:therapeutic use*; D013997:Time Factors
D001562:Benzimidazoles; D002121:Calcium Channel Blockers; D010919:Placebos; D013764:Tetrahydronaphthalenes; D020748:Mibefradil