Randomized Placebo-Controlled Withdrawal Study of Amlodipine in Agina Pectoris

Abstract

OBJECTIVES: To assess the antianginal and antiischemic efficacy, safety, and the potential for tolerance or withdrawal effects of amlodipine. BACKGROUND: The slow onset of action and long half-life of amlodipine may help avoid withdrawal effects such as the exacerbation of angina and precipitation of myocardial seen with beta-blockers. METHODS: After a 2-week single-blind placebo run-in period, 226 patients with stable exertional angina pectoris were given amlodipine (starting at 5 mg day(minus sign1) and titrated to 10 mg day(minus sign1)) in a single-blind fashion for 8 weeks. One hundred seventy-two responders (greater-than-or-equal7% improvement in symptom-limited exercise time) entered a 4-week double-blind withdrawal phase and randomly received continued treatment with amlodipine (n = 91) or placebo (n = 81). RESULTS: Treatment with amlodipine increased the exercise capacity by 14% and improved time to angina onset by 25% and time to 1-mm ST segment deviation by 18%. These variables remained essentially unchanged at the end of the 4-week withdrawal phase for the group continued on amlodipine (+0.8%, +3.2%, and +2.0%, respectively) but decreased for the group on placebo (minus sign5.8%, minus sign9.8%, and minus sign11.0%, respectively) (p < 0.001 between groups, all assessments) to values similar to those obtained during the initial placebo run-in period. Approximately one-third of the patients responded to 5 mg amlodipine during single-blind therapy and according to "usual clinical practice" remained on this dose. The results of randomized withdrawal in the subgroup receiving 5 mg also favored amlodipine over placebo. Side effects were reported by 47% of patients on amlodipine and by 22% of patients receiving placebo. The most frequently reported side effects for