Time to arrhythmic, ischemic, and heart failure events: Exploratory analyses to elucidate mechanisms of adverse drug effects in the Cardiac Arrhythmia Suppression Trial

• Published in: The American heart journal Vol. 130; no. 1; pp. 71 - 79
• Main Authors: Hallstrom, Alfred P., Anderson, Jeffrey L., Carlson, Mark, Davies, Richard, Greene, H.Leon, Kammerling, James M., Romhilt, Donald W., Duff, Henry J., Huther, Melissa
• Format: Journal Article
• Language: English
• Published: New York, NY Mosby, Inc 01.07.1995; Elsevier
• Subjects: Anti-Arrhythmia Agents - adverse effects; Antiarythmic agents; Arrhythmias, Cardiac - etiology; Arrhythmias, Cardiac - mortality; Arrhythmias, Cardiac - prevention & control; Biological and medical sciences; Cardiovascular system; Double-Blind Method; Encainide - adverse effects; Flecainide - adverse effects; Heart Failure - etiology; Heart Failure - mortality; Heart Failure - prevention & control; Humans; Medical sciences; Moricizine - adverse effects; Myocardial Infarction - complications; Myocardial Infarction - drug therapy; Myocardial Infarction - mortality; Myocardial Ischemia - etiology; Myocardial Ischemia - mortality; Myocardial Ischemia - prevention & control; Pharmacology. Drug treatments; Risk Factors; Survival Analysis; Time Factors; Heart; Human; Secondary effect; Controlled therapeutic trial; Antiarrhythmia agent
• ISSN: 0002-8703; 1097-6744
• DOI: 10.1016/0002-8703(95)90238-4

In this study we investigated the time to the first arrhythmic, ischemic, or failure event for encainide-flecainide and moricizine versus their respective placebo comparison groups in the Cardiac Arrhythmia Suppression Trial. The purpose was to explore possible mechanisms for the excessive deaths associated with active therapy that have been previously reported. Differences were noted between the active drugs. In particular, encainide-flecainide appeared to convert an ischemic event into death in more cases and more promptly than moricizine. However, the excessive deaths noted on encainide-flecainide were as likely to occur subsequent to a failure event as an ischemic event; for both encainide-flecainide and moricizine, the vast majority of excess deaths appeared to be the result of an increase in arrhythmia events without any protective effect of the drug. We were unable to identify any specific mechanism to explain the adverse effect of encainide and flecainide.