Cardiac arrhythmia suppression trial (CAST): Interpretation of the findings and effect on drug development and prescribing practices

The presence of ventricular ectopic activity in the post-myocardial infarction (post-MI) patient, especially when accompanied by left ventricular dysfunction, has been associated with a high incidence of sudden cardiac death. The Cardiac Arrhythmia Suppression Trial (CAST) was performed to test the hypothesis that premature ventricular complex (PVC) suppression in patients in the post-MI setting might reduce the incidence of sudden cardiac death. In patients treated with encainide HCl or flecainide acetate, total mortality at 10 months was 7.7%, compared to only a 3% overall mortality among patients receiving placebo. The increase in mortality and sudden cardiac death with these two drugs raised the question of whether PVC suppression in this group of patients should be attempted. Extension of this trial (CAST II) with moricizine HCl alone resulted in a trend toward increased mortality in the moricizine-treated group. Extrapolation of the results of this study to other patient groups has resulted in a change of physicians' habits in prescribing antiarrhythmics. The results of CAST and CAST II suggest that, except for the use of β-blockers, antiarrhythmic drug treatment in post-MI patients with asymptomatic ventricular arrhythmias might be detrimental. The results of these studies should not be extrapolated to the chronic setting of patients with nonischemic cardiac arrhythmias and supraventricular tachycardia.