Prophylactic antiarrhythmic therapy for the prevention of sudden death in high-risk patients: drugs and devices

Randomized clinical trials have been used for over a decade to elucidate wa ys to prevent sudden death. The Cardiac Arrhythmia Suppression Trial (CAST) was designed to show that Vaughan-Williams class I antiarrhythmic drug the rapy would reduce the risk of death by means of suppression of ventricular arrhythmia. It was discovered however, that the drugs used in this trial, e ncainide and flecainide, increased mortality. Subsequently, a metaanalysis of previous trials using other drugs of the same class clearly indicated th e likelihood that all class I agents have a potential for harm and almost n o potential for benefit. Amiodarone gradually became established in the 197 0s and 1980s as a potent antiarrhythmic drug for patients with recurrent su stained ventricular tachycardia (VT). Because of its effectiveness in this group of patients it was logical to evaluate the drug for prophylaxis. From 1985-95, 13 randomized controlled trials of amiodarone were performed. A m eta-analysis of these trials has recently been reported. There were eight p ost-myocardial infarction (MI) and five heart failure trials giving rise to a total of 6553 patients. With amiodarone, total mortality was significant ly reduced by 13% (P=0.03). Arrhythmic death was significantly reduced by a lmost 30% (P=0.003). There was no effect on non-arrhythmic deaths. Amiodaro ne was generally well tolerated although in some trials there was a high ra te of study drug discontinuation. A metaanalysis of the post-MI beta-blocke r trials showed a reduction in total mortality of 20%. A very important asp ect of the effect of beta-blockers is in the reduction of deaths due to arr hythmia. Recently, two large, randomized, controlled trials in high-risk pa tients demonstrated that dofetilide, a purely class III agent, has little e ffect on mortality. Two prophylactic implantable cardiac defibrillator (ICD ) trials have been performed. The Multicenter Automatic Defibrillator Trial (MADIT) studied patients with a law left ventricular ejection fraction and nonsustained ventricular tachycardia. Eligible patients were to have induc ible VT using programmed electrical stimulation, non-suppressible by procai namide. The MADIT reported a marked reduction in overall mortality when ICD therapy was compared with conventional drug therapy care. The Coronary Art ery Bypass Graft (CABG)-Patch trial, however, found no difference in mortal ity amongst high-risk CABG patients receiving ICD therapy compared to those undergoing conventional therapy. The results of the MADIT have given hope that ICD therapy may be an effective prophylactic treatment. However, doubt s remain because of the unimpressive results of The CABG-Patch trial. Sever al ongoing studies are evaluating the benefits of prophylactic ICD therapy in both post-MI and congestive heart failure patients.