Lessons from antiarrhythmic trials involving class III antiarrhythmic drugs

Beta-adrenergic blockers reduce mortality and sudden death in patients convalescing from myocardial infarction, and probably in patients with heart failure. However, the notion that class I antiarrhythmic drugs might save lives by suppressing the triggers of life-threatening ventricular arrhythmias was proved incorrect when the Cardiac Arrhythmia Suppression Trial (CAST) demonstrated that patients, whose ventricular ectopics were successfully suppressed by a number of class I antiarrhythmic drugs, died more readily than similar patients when treated with drugs rather than the placebo. Attention was diverted to class III antiarrhythmic drugs for patients with a poor ejection fraction who survived myocardial infarction and those with heart failure. A preliminary metaanalysis of 3 trials (Basel Antiarrhythmic Study of Infarct Survival [BASIS], Polish Amiodarone Trial [PAT], and the Canadian Amiodarone Myocardial Infarction Arrhythmia Trial [CAMIAT]) suggested that amiodarone might reduce arrhythmic and all-cause mortality in high-risk post-myocardial-infarction (MI) patients. BASIS suggested that this was only true for patients with preserved ventricular function. Nevertheless, 2 major trials were instituted: the European Myocardial Infarct Amiodarone Trial (EMIAT) and the CAMIAT. Both reported similar results except that patients recruited because of high-density ventricular ectopy seemed to benefit a little more from amiodarone than did patients with poor ventricular function. Detailed analysis of these trials revealed important insights into the value of amiodarone.