The Cardiac Arrhythmia Suppression Trial (CAST)

Objectives:

The Cardiac Arrhythmia Suppression Trial sought to evaluate the efficacy and safety of arrhythmia suppression therapy in patients with asymptomatic or mildly symptomatic ventricular arrhythmia after myocardial infarction.

Background:

A significant risk factor for mortality in post-MI patients is the presence of ventricular premature depolarizations. Although some anti-arrhythmic drugs, such as acute intravenous and long term beta blockers, had been shown to reduce mortality, it was unclear if arrhythmia suppression led to prolonged survival or if other effects contributed to the decreased mortality. The Cardiac Arrhythmia Pilot Study was initiated in 1982 to assess the feasibility of identifying post-MI patients with ventricular arrhythmia and whether one or more drugs could be found to effectively and safely reduce ventricular premature depolarizations. The pilot study evaluated four active drugs (Encainide, Ethmozine, Flecainide, Imipramine) against placebo in 500 patients. Based on the results of the pilot study a full scale trial began enrolling patients in 1987.

Subjects:

CAST was designed as a randomized, double-blind trial. Patients within 90 days post-MI were first screened for arrhythmia via an ambulatory electrocardiographic (Holter) recording with a minimum of 18 hours of data. Eligibility was based on six or more ventricular depolarizations per hour and an ejection fraction of 0.55 or less. For patients 90 days or more post-MI, eligibility was based on six or more ventricular depolarizations per hour and an ejection fraction of 0.40 or less. Patients were not eligible for the study if they had ventricular arrhythmia causing more severe symptoms resulting from hemodynamic compromise, any unsustained ventricular tachycardia, contraindications to any study drug, or other life threatening conditions. Eligible patients first underwent an open label titration phase to evaluate effective suppression of arrhythmia. Eligible patients tolerant of the drugs and achieving a reduction of 80 percent or more in ventricular depolarizations and 90 percent or more in runs of unsustained ventricular tachycardia were randomized into the trial. Patients were randomized to receive placebo or treatment with Encainide, Flecainide, or Moricizine.

Conclusions:

After less than one year of followup the Encainide and Flecainide arms of the trial were stopped due to increased mortality and nonfatal cardiac arrests compared to placebo. The protocol was modified and the study continued as CAST II and compared Moricizine to placebo. The CAST II study was also stopped early due to excess mortality and nonfatal cardiac arrests in the Moricizine arm compared to placebo. (NEJM, 1989; 321:406-12, NEJM, 1992; 327:227-33).