Cardiac Arrhythmia Suppression Trial [CAST]

Abstract

The Cardiac Arrhythmia Suppression Trial (CAST) represents a pivotal moment in the evolution of evidence-based medicine. Conducted in the late 1980s, the trial aimed to evaluate whether pharmacological suppression of ventricular arrhythmias following myocardial infarction could reduce mortality. While class I antiarrhythmic agents such as encainide, flecainide, and moricizine were highly effective in suppressing premature ventricular contractions (PVCs), the trial revealed a paradoxical increase in mortality among treated patients. This unexpected outcome led to early termination of the study and highlighted the limitations of surrogate endpoints in clinical research. CAST fundamentally reshaped clinical decision-making, emphasizing the importance of patient-centered outcomes such as survival rather than physiological or laboratory improvements alone. The Cardiac Arrhythmia Suppression Trial (CAST) was a landmark randomized controlled trial designed to evaluate whether suppression of ventricular arrhythmias after myocardial infarction could reduce mortality. Although antiarrhythmic drugs effectively suppressed premature ventricular contractions (PVCs), the study unexpectedly demonstrated increased mortality in treated patients, leading to early termination. This trial highlighted the limitations of surrogate endpoints and fundamentally changed clinical research and cardiology practice.