CIRCADIAN PATTERN OF ARRHYTHMIC DEATH IN PATIENTS RECEIVING ENCAINIDE, FLECAINIDE OR MORICIZINE IN THE CARDIAC-ARRHYTHMIA SUPPRESSION TRIAL(CAST)

Objectives. The purpose of this study was to assess the effect of anti arrhythmic 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 measur es. 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 Supp ression Trial (CAST) was a multicenter double-blind, placebo-controlle d study designed to determine whether suppression of ventricular ectop ic activity by means of antiarrhythmic drugs (encainide, flecainide or moricizine) after acute myocardial infarction would reduce the incide nce of arrhythmic death. Results. The trial was terminated prematurely because of an unexpectedly high mortality rate in the active treatmen t group. The onset of arrhythmic death in this group (in patients not receiving beta-adrenergic blocking agents) displayed a bimodal variati on, with significant pecks in midmorning and late afternoon/early even ing. More than half of the symptomatic events were accompanied by angi nalike symptoms. Approximately 30% of all events occurred within 2 h o f awakening. Conclusions. Our data suggest the possibility of a comple x interaction among antiarrhythmic drugs, sympathetic nervous system a ctivation and acute myocardial ischemia. Planning of future antiarrhyt hmic drug trials will need to take this information into account.