The Cardiac Arrhythmia Suppression Trial (CAST) was a randomized, placebo-controlled study that examined the effect of three antiarrhythmic drugs on patients with ventricular ectopy and nonsustained ventricular tachycardia after myocardial infarction. A preliminary report in 1989 announced that two arms of the trial, using flecainide and encainide, were stopped because of excess mortality in treated patients (see Journal Watch accession number 890818001). This report presents the final analysis of the data on the two drugs.
After a mean follow-up of 10 months, 63 of 755 patients receiving flecainide or encainide and 26 of 743 patients receiving placebo had died -- a highly significant difference. Two-thirds of the deaths were caused by arrhythmias, and about half of the remaining deaths were caused by acute MI. Surprisingly, however, patients taking active drugs did not have a higher rate of nonfatal endpoints during the study (e.g., ventricular tachycardia without arrest, recurrent MI, syncope, need for a pacemaker, etc.). Because of this discrepancy between fatal and nonfatal endpoints, the authors acknowledge that the exact mechanism of the increased mortality associated with flecainide and encainide remains unclear.
The third arm of the trial, comparing moricizine and placebo, is continuing under the designation CAST II.
Published in Journal Watch General Medicine March 22, 1991
Echt DS et al. Mortality and morbidity in patients receiving encainide, flecainide, or placebo: the Cardiac Arrhythmia Suppression Trial. N Engl J Med 1991 Mar 21 324 781-788.
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