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

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 antianginal therapy: either beta 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 100-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 dose 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 anti-ischemic 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 beta-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.

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.

Prolonged dilation with an autoperfusion balloon catheter for refractory acute occlusion related to percutaneous transluminal coronary angioplasty.

OBJECTIVES: Efficacy and safety of redilation by an autoperfusion balloon catheter over several hours were investigated in this retrospective and observational study. BACKGROUND: Acute occlusion, refractory to redilation, is a serious complication of coronary angioplasty. METHODS: Of 1,123 patients who underwent angioplasty, 83 had a refractory acute occlusion. Thiry-five patients were treated with extended dilation. Seven had stable, 19 unstable and 6 postinfarction angina and 3 had an acute infarction at the time of angioplasty. The duration of dilation was (mean +/- SD) 17 (+/- 6) h. RESULTS: Angiographically successful redilation, with a mean residual percent diameter stenosis of 13.5% (+/- 11.6%), was achieved in 22 (67.7%) of 34 patients. Five patients underwent bypass surgery. Three patients, who were poor surgical candidates, died. There was one new Q wave infarction and one death that occurred during extended dilation; one death and four operations were related to reocclusion immediately (< or = 30 min) after catheter withdrawal; and one death and one operation were related to in-hospital reocclusion. Overall success, defined as angiographic success and freedom from major events, was obtained in 20 (57%) of 35 patients (95% confidence interval 41% to 73%). Of the variables studied, only multilesion dilation was significantly (p = 0.018) associated with an unfavorable outcome. During a mean follow-up period of 13.8 (+/- 6.1) months, two patients underwent repeat angioplasty, one sustained an infarction and three underwent elective bypass surgery. CONCLUSIONS: In approximately half of the patients (20 [57%] of 35), an initial angioplasty failure due to refractory occlusion could be reverted to a successful procedure by prolonged dilation with an autoperfusion balloon catheter.