Amlodipine versus Diltiazem CR in the Reduction of the Total Ischemic Burden: The Circadian Anti-Ischemia Program in Europe (CAPE) II Trial — Clinical Rationale and Methodology

Abstract

The Circadian Anti-ischemia Program in Europe (CAPE) trial was a large, 10-week, double-blind study of the antiischemic effects of the third-generation calcium antagonist, amlodipine, in patients with chronic stable angina. The study showed that, compared with the addition of placebo to conventional medical therapy (if any), the addition of amlodipine significantly reduced the total ischemic burden. Both symptomatic and asymptomatic ischemic events were reduced, over 24 hours, with no change in the heart rate profile. The next logical step is to compare amlodipine with other agents, as monotherapy and in combination therapy, which is the basis for the CAPE II trial. This European multicenter project will recruit patients with coronary artery disease and chronic stable angina in order to compare the efficacy of the intrinsically long-acting amlodipine with an artificially extended-release formulation of diltiazem, a calcium antagonist with a short plasma half-life. The impact of these agents will also be compared during irregular dosing periods. An agent with an intrinsically long half-life, such as amlodipine, may maintain better clinical efficacy than a short-acting drug with a prolonged delivery system in these circumstances. The CAPE II trial will investigate whether this results in improved management of the circadian pattern of transient myocardial ischemia. In addition, basic therapy will be augmented by the addition of a beta-blocker to amlodipine and the addition of a nitrate to diltiazem to evaluate which of these frequently prescribed treatment approaches results in optimal ischemia suppression. Both the subjective endpoints of angina and patient well-being, as well as the objective measures of myocardial ischemia in exercise testing and ambulatory electrocardiography (ECG) monitoring, will be employed. Answers to these issues will help to define the optimal medical approach to ischemia suppression in patients with coronary artery disease and will complement the findings from large-scale prognosis trials currently being performed.