Amlodipine in chronic stable angina: Results of a multicenter double-blind crossover trial

The efficacy and safety of amiodipine, 10 mg, a new long-acting calcium antagonist, was compared with placebo in 103 patients with stable angina pectoris in a multicenter double-blind crossover study. The trial consisted of an initial 2-week single-blind placebo period followed by a first period of 4 weeks at double-blind therapy, which was followed by a 1 week washout perioid and then a second 4-week double-blind period after treatments were crossed over. Twenty-four-hour Holter electrocardiographic monitoring was carried out in 12 patients at three centers. In the first double-blind period amiodipine prodcued a significantly greater increase in symptom-limited exercise duration (amiodipine 478.5 to 520.6 vs placebo 484.6 to 485.2 seconds; change +8.8% vs +0.1%, respectively; p = 0.0004) and total work (amiodipine 2426 to 2984 vs placebo 2505 to 2548 kilopondmeters; change +24% vs +1.7%, respectively; p = 0.0006) and a decrease in angina attack frequency (from 3 to 1 per week; p = 0.016) and nitroglycerin consumption (from 2 to 0.5 tablets/wk; p = 0.01) compared with placebo. Holter monitoring revealed significant reductions in numbers (amiodipine 4.65 to 2.22 vs placebo 1.84 to 1.54; change +52% vs +84%, respectively; p = 0.06), absolute total area (amiodipine 87.66 to 11.43 vs placebo 5.76 to 35.24; change +87% vs +513%, respectively; p = 0.02), and duration (amiodipine 12.29 to 2.95 vs 1.66 to 7.74 seconds; change +76% vs +367%, respectively; p = 0.008) of ST-segment depressions after treatment with amiodipine compared with placebo. After the treatments were crossed over changes continued to favor amiodipine. However, there were no significant changes by Holter monitoring in any of the ST-segment parameters during the period after the crossover. The smaller changes with amiodipine during the period after the crossover may be the result of the long half-life of amiodipine or an exercise training effect. The most frequently reported side effects with amiodipine were headache (11%) and edema (8%). We conclude that amiodipine therapy is well tolerated and that it demonstrates antiischemic and antianginal efficacy in the management of stable angina.