Implications of the Cardiac Arrhythmia Suppression Trial for antiarrhythmic drug treatment

Abstract

The Cardiac Arrhythmia Suppression Trial (CAST) is a randomized, placebo-controlled, double-blind, multicenter clinical trial involving 27 centers and more than 100 hospitals in North America and Europe to test the 1-tailed hypothesis that suppression of ventricular arrhythmias in patients with left ventricular dysfunction after myocardial infarction will reduce arrhythmic death. Since April 18, 1989, the CAST is enrolling patients aged less than 80 years with greater than or equal to 6 ventricular premature complexes and left ventricular ejection fraction less than or equal to 40%. Sustained ventricular tachycardia, class IV congestive heart failure or class IV angina pectoris are exclusion criteria. During a prerandomization period, antiarrhythmic drugs are titrated to suppress ventricular arrhythmias. If greater than or equal to 80% suppression is achieved during open-label titration, patients are randomized to the effective dose or to a matched placebo. If only partial suppression (1 to 79%) is achieved, patients are eligible for a substudy that randomizes them to the best dose found during open-label titration or to placebo. The only patients not randomized to treatment are those with increased arrhythmias or drug intolerance during titration. On April 18, 1989, encainide and flecainide were removed from the CAST because these drugs increased the death rate 2.5-fold. There were no imbalances in baseline risk variables between the encainide/flecainide group and the placebo group that might explain the adverse treatment effect. There was remarkable uniformity of the adverse effect across all subgroups. There were no subgroups that benefited from treatment; all were either harmed or not evaluable.(ABSTRACT TRUNCATED AT 250 WORDS)