This study assessed the safety, tolerability, and efficacy of mibefradil when added to β-blocker monotherapy in patients with chronic stable angina pectoris. Two hundred five patients were randomized to receive double-blind treatment with either placebo (n = 70), mibefradil 25 mg (n = 67), or mibefradil 50 mg (n = 68) for 2 weeks. Exercise tolerance tests (ETTs) were performed at the end of the run-in (baseline) and double-blind treatment periods, and patients maintained an anginal diary. Compared with placebo, treatment with mibefradil 50 mg resulted in significant increases in exercise duration (36 ± 51 seconds; p = 0.036), time to onset of angina (48 ± 65 seconds; p = 0.002), and time to persistent 1-mm ST-segment depression (47 ± 77 seconds; p = 0.004). Greater reductions in heart rate, blood pressure, and the rate-pressure product were more apparent at each stage of the ETT in the 50-mg mibefradil group than in the placebo group. Daily treatment with mibefradil 50 mg was associated with a significant decrease in the number of weekly anginal attacks (−2.1 ± 4.0, p = 0.020) compared with placebo. The addition of mibefradil to existing β-blocker therapy was well tolerated. Dizziness was the most frequently reported adverse event in the mibefradil 50-mg dose, and occurred with an incidence of 4.4%. The addition of mibefradil 50 mg, administered once daily, to patients on stable β-blocker therapy produced additive antianginal and anti-ischemic effects and was well tolerated.

The purpose of this study was to assess efficacy, safety, and tolerability of mibefradil, a novel calcium antagonist, when added to β-blocker monotherapy in patients with chronic stable angina pectoris. The addition of mibefradil 50 mg administered once daily produced additive antianginal and anti-ischemic effects and was well tolerated.