Secondary prevention of sudden death: the Dutch study, the antiarrhythmics versus implantable defibrillator trial, the cardiac arrest study Hamburg, and the Canadian implantable defibrillator study

Although indisputably effective in the prevention of sudden death, use of implantable cardioverter defibrillator (ICD) therapy may not necessarily affect all-cause mortality, as most patients at risk also present with severely depressed left ventricular dysfunction. Correction of the sudden death risk in these patients creates a new clinical condition in need of a careful assessment. Should all-cause mortality be affected by the expected reduction in sudden death rate associated with ICD therapy, issues of critical importance, such as the time extent of life prolongation and the associated quality of life, still remain to established. To investigate the potential benefit of ICD therapy compared with antiarrhythmic drug treatment, 4 prospective studies—the Dutch trial, the Antiarrhythmics Versus Implantable Defibrillators (AVID) study, the Cardiac Arrest Study Hamburg (CASH), and the Canadian Implantable Defibrillator Study (CIDS)—have been conducted in which patients with documented sustained ventricular arrhythmia were randomized to 1 of these 2 treatment strategies. The enrollment criteria differed in these 4 studies: (1) in the Dutch trial, they included cardiac arrest secondary to a ventricular arrhythmia, old (>4 weeks) myocardial infarction, and inducible ventricular arrhythmia; (2) in AVID and CIDS, ventricular fibrillation or poorly tolerated ventricular tachycardia; and (3) in CASH, cardiac arrest secondary to a ventricular arrhythmia regardless of the underlying disease. With regard to the antiarrhythmic drugs, the Dutch trial tested class I and III agents, whereas AVID and CIDS compared ICD therapy with class III agents (mostly amiodarone). In CASH, 3 drug subgroups were investigated: propafenone, amiodarone, and metoprolol. All trials used all-cause mortality as the primary endpoint. Data from these trials provide support for ICD as a therapy superior to antiarrhythmic drugs in prolonging survival in patients meeting the entry criteria. This review briefly summarizes the methods, results, limitations, and clinical implications of these 4 studies.