Amlodipine reduces transient myocardial ischemia in patients with coronary artery disease: Double-blind circadian anti-ischemia program in Europe (CAPE trial)

Abstract

Objectives. This study was carried out to determine the effect of the once-daily calcium channel blocking agent amlodipine (halflife 35 to 50 h) on the circadian pattern of myocardial ischemia in patients with chronic stable angina.Background. Myocardial ischemia during normal daily life, both symptomatic and asymptomatic, has been associated with increased risk of cardiovascular morbidity and mortality, and the circadian pattern parallels that for myocardial infarction and sudden death.Methods. The Circadian Anti-Ischemia Program in Europe (CAPE) was a large, 10-week international (63 sites), doubleblind, parallel study. After a 2-week, single-Mind placebo phase, during which stable doses of antianginal treatment were maintained (beta-adrenergic blocking agents in 65% of patients), patients with chronic stable angina with at least three attacks of angina per week, with at least four ischemic episodes or ≥ 20 min of ST segment depression in 48 h of Holter monitoring, were randomized to receive treatment with either 5 mg/day of amlodipine or placebo (2:1 randomization). The dose was increased to 10 mg/day after 4 weeks. During week 7 of treatment, 48-h ambulatory ECG monitoring was repeated.Results. Three hundred fifteen of 1,160 patients screened were eligible, and 250 had complete evaluable data. Compared with placebo, amlodipine significantly reduced both the frequency of ST segment depression episodes (60% for amlodipine vs. 44% for placebo, p = 0.025) and total integrated ST ischemic area (62% mm-min vs. 50% mm-min, p = 0.042). Amlodipine reduced ischemia over the 24 h with the intrinsic circadian pattern maintained. In addition, diary data showed a significant reduction in angina (70% for amlodipine vs. 44% for placebo, p = 0.0001) and in nitroglycerin consumption (67% vs. 22%, respectively, p = 0.0006). Amlodipine and placebo demonstrated similar safety profiles (adverse events 17.3% for amlodipine and 13.3% for placebo; discontinuation rates due to adverse events were 2% vs. 4.4%, respectively).Conclusions. Once-daily amlodipiae, when added to background treatment, significantly reduced both symptomatic and asymptomatic ischemic events over 24 h in patients with chronic stable angina.