A decade of clinical trials: CAST to AVID

The last 10 years have seen unprecedented advances in the management of pat ients with life-threatening arrhythmias. With the advent of large-scale ran domized trials, there have been significant advances in the understanding o f ventricular arrhythmias. These have radically changed the physician's app roach to patients presenting with arrhythmia. Initially, the electrophysiol ogical testing of drugs led to the opinion that antiarrhythmic agents had l ittle effect in patients with malignant ventricular arrhythmias. Recent ran domized trials (the Cardiac Arrest Study in Hamburg, the Antiarrhythmic Ver sus Implantable Defibrillator trial, and the Canadian Implantable Defibrill ator Study) compared the long-term effect of implantable cardiac defibrilla tors (ICDs) with drug therapy in high-risk subjects. This group of patients included cardiac arrest survivors and patients with poorly-tolerated ventr icular tachyarrhythmias. The results of these randomized trials indicated a trend towards increased efficacy of ICD therapy in improving survival. Studies have also been conducted in the field of primary prevention of sudd en death. Target populations in these trials were ischaemic patients who ha d suffered a previous myocardial infarction (MI). Candidates for antiarrhyt hmic prevention were defined using risk markers for sudden death; the marke rs were usually low ejection fraction and complex ventricular ectopic activ ity, documented by ambulatory electrocardiographic recordings. Drugs depres sing conduction (class I) or prolonging repolarization (class Ill) both pro ved harmful after MI by causing increased mortality in drug-treated patient s (Cardiac Arrhythmia Suppression Trial and the Survival With oral d-sotalo l studies). The effect of amiodarone was then investigated. Two large trial s (the European Myocardial Infarct Amiodarone Trial and the Canadian Amioda rone Myocardial Infarction Arrhythmia Trial), conducted in post-MI patients , failed to show that amiodarone was of clear-cut benefit in survival. In t wo other trials involving patients with congestive heart failure, the Grupo de Estudio de la Sobrevida en la Insuficiencia Cardiaca en Argentina, and the Congestive Heart Failure:Survival Trial of Antiarrhythmic Therapy resul ts were conflicting, making it difficult to draw any firm conclusions. A re cent metaanalysis of 13 randomized trials of prophylactic amiodarone showed an overall reduction in total mortality. However, the high rate of drug di scontinuation in these studies is a matter for concern. The role of ICDs in the primary prevention of sudden death remains to be defined. Results of t he Multicenter Automatic Defibrillator Trial showed that ICD therapy had a beneficial effect in patients at particularly high risk of sudden arrhythmi c death. However, further investigation is required.