Contemporary Clinical Trials in Ventricular Tachycardia and Fibrillation: Implications of ESVEM, CASCADE, and CASH for Clinical Management

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Abstract
Recent clinical trials in patients with ventricular tachycardia (VT) or fibrillation (VF) have occurred in the setting of the disappointing results of postinfarction secondary prevention studies using Class I antiarrhythmics (e.g., CAST). ESVEM addressed in a randomized trial whether electrophysiologic study (EPS) or Holter monitoring (HM) is a more accurate predictor of long-term antiarrhythmic drug efficacy in VT/VF patients (N=486) and what the relative efficacy of various antiarrhythmic agents is for VT/VF. Surprisingly, arrhythmia recurrence rates were not significantly different by the method of determining an efficacy prediction. However, arrhythmia recurrence and mortality were lower (by about 50% at 1 year) in patients treated with sotalol (a mixed Class II/III agent) than with other drugs (Class I). CASCADE evaluated empiric amiodarone versus guided (EPS or HM) standard (Class I) therapy in survivors of out-of-hospital cardiac arrest due to VF. The primary endpoint of cardiac death, resuscitated VF, or syncopal shock (in ICD patients) was reduced by amiodarone compared with conventional therapy (9% vs 23% at 1 year). An interim report of the ongoing CASH study suggested in 230 survivors of cardiac arrest that propafenone (Class IC) provided less effective prophylaxis (approximately 20% 1-year mortality) compared with randomly assigned therapies with amiodarone, metoprolol, or an ICD (approximately 14% mortality rates) and was excluded from further study. These studies have led to a paradigm shift in the approach to antiarrhythmic therapy of VT/VF: drugs with antisympathetic plus Class III (refractoriness prolonging) action (i.e., sotalol, amiodarone) are superior to traditional drugs with Class I( conduction slowing) effects, even when guided by EPS or HM.

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