Circadian pattern of arrhythmic death in patients receiving encainide, flecainide or moricizine in the Cardiac Arrhythmia Suppression Trial (CAST).
OBJECTIVE
The purpose of this study was to assess the effect of antiarrhythmic drugs on the timing of arrhythmic death.


BACKGROUND
Sudden cardiac death remains a problem of epidemic proportions. Delineating its pathophysiology is an important step in devising preventive measures. Previous studies have shown a circadian pattern of onset of sudden cardiac death. The effect of antiarrhythmic drugs on this pattern has not been systematically studied.


METHODS
The Cardiac Arrhythmia Suppression Trial (CAST) was a multicenter double-blind, placebo-controlled study designed to determine whether suppression of ventricular ectopic activity by means of antiarrhythmic drugs (encainide, flecainide or moricizine) after acute myocardial infarction would reduce the incidence of arrhythmic death.


RESULTS
The trial was terminated prematurely because of an unexpectedly high mortality rate in the active treatment group. The onset of arrhythmic death in this group (in patients not receiving beta-adrenergic blocking agents) displayed a bimodal variation, with significant peaks in midmorning and late afternoon/early evening. More than half of the symptomatic events were accompanied by anginalike symptoms. Approximately 30% of all events occurred within 2 h of awakening.


CONCLUSIONS
Our data suggest the possibility of a complex interaction among antiarrhythmic drugs, sympathetic nervous system activation and acute myocardial ischemia. Planning of future antiarrhythmic drug trials will need to take this information into account.
Peters
R W
RW
Department of Medicine, Baltimore Department of Veterans Affairs Medical Center, Maryland 21201.
Mitchell
L B
LB
Brooks
M M
MM
Echt
D S
DS
Barker
A H
AH
Capone
R
R
Liebson
P R
PR
Greene
H L
HL
D000368:Aged; D000889:Anti-Arrhythmia Agents / Q000009:adverse effects / Q000627:therapeutic use*; D001145:Arrhythmias, Cardiac / Q000188:drug therapy / Q000401:mortality* / Q000503:physiopathology; D001241:Aspirin / Q000627:therapeutic use; D002940:Circadian Rhythm / Q000502:physiology*; D016757:Death, Sudden, Cardiac / Q000453:epidemiology*; D004311:Double-Blind Method; D016700:Encainide / Q000627:therapeutic use; D005424:Flecainide / Q000627:therapeutic use; D006323:Heart Arrest / Q000453:epidemiology* / Q000503:physiopathology; D006801:Humans; D016293:Moricizine / Q000627:therapeutic use; D013564:Sympathetic Nervous System / Q000503:physiopathology
D000889:Anti-Arrhythmia Agents; D016293:Moricizine; D005424:Flecainide; D001241:Aspirin; D016700:Encainide