AMLODIPINE IN CHRONIC STABLE ANGINA - RESULTS OF A MULTICENTER DOUBLE-BLIND CROSSOVER TRIAL

The efficacy and safety of amlodipine, 10 mg, a new long-acting calciu m antagonist, was compared with placebo in 103 patients with stable an gina pectoris in a multicenter double-blind crossover study. The trial consisted of an initial 2-week single-blind placebo period followed b y a first period of 4 weeks of double-blind therapy, which was followe d by a 1 week washout period and then a second 4-week double-blind per iod after treatments were crossed over. Twenty-four-hour Holter electr ocardiographic monitoring was carried out in 12 patients at three cent ers. In the first double-blind period amlodipine produced a significan tly greater increase in symptom-limited exercise duration (amlodipine 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 (amlodipine 2426 to 2984 v s placebo 2505 to 2548 kilopondmeters; change +24% vs +1.7%, respectiv ely; 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 ta blets/wk; p = 0.01) compared with placebo. Holter monitoring revealed significant reductions in numbers (amlodipine 4.65 to 2.22 vs placebo 1.84 to 1.54; change -52% vs +84%, respectively; p = 0.06), absolute t otal area (amlodipine 87.66 to 11.43 vs placebo 5.76 to 35.24; change -87% vs +513%, respectively; p = 0.02), and duration (amlodipine 12.29 to 2.95 vs 1.66 to 7.14 seconds; change -76% vs +367%, respectively; p = 0.008) of ST-segment depressions after treatment with amlodipine c ompared with placebo. After the treatments were crossed over changes c ontinued to favor amlodipine. However, there were no significant chang es by Holter monitoring in any of the ST-segment parameters during the period after the crossover. The smaller changes with amlodipine durin g the period after the crossover may be the result of the long half-li fe of amlodipine or an exercise training effect. The most frequently r eported side effects with amlodipine were headache (11%) and edema (8% ). We conclude that amlodipine therapy is well tolerated and that it d emonstrates antiischemic and antianginal efficacy in the management of stable angina.