THE CARDIAC-ARRHYTHMIA SUPPRESSION TRIAL - 1ST CAST ... THEN CAST-II

The Cardiac Arrhythmia Suppression Trial (CAST) was a study designed t o test the hypothesis that suppression of ventricular premature comple xes after a myocardial infarction would improve survival. Preliminary results showed that suppression of ventricular premature complexes wit h encainide and flecainide worsened survival, and the CAST continued a s the CAST-II with moricizine compared with its placebo. The protocol for the CAST-II was changed to attempt to enroll patients more likely to experience serious arrhythmias. The enrollment time was narrowed to 4 to 90 days after myocardial infarction; the qualifying ejection fra ction was lowered to less-than-or-equal-to 0.40; a higher dose of mori cizine could be used; early titration itself was double-blind with a p lacebo, and the definition of disqualifying ventricular tachycardia wa s changed to allow patients with more serious arrhythmias to be entere d into the trial. The Cardiac Arrhythmia Suppression Trial-II was subs equently terminated prematurely because 1) patients treated with moric izine had an excessive cardiac mortality rate during the 1st 2 weeks o f exposure to the drug, and 2) there appeared to be little chance of s howing a long-term survival benefit from treatment with moricizine. Th is report outlines the rationale behind the Cardiac Arrhythmia Suppres sion Trial and the reasons for selection of the drugs used in the CAST and CAST-II.