ALIVE Trial: How Is This Trial Design Different?
The development of the ALIVE study design is based upon an analysis of previous studies attempting pharmacologic reduction of arrhythmic death after acute myocardial infarction (MI). Historically, antiarrhythmic agents with predominant class I or class III (Vaughan Williams classification) activity have been tested and shown in several post-MI clinical trials to be ineffective, or even harmful, in terms of excessive morbidity and mortality because of proarrhythmic effects or end-organ toxicities [1–6]. Examples of such agents and trials include flecainide and encainide in Cardiac Arrhythmia Suppression Trial (CAST) , moricizine in CAST II , D-sotalol in the Survival With Oral D-Sotalol (SWORD) trial [3, 4], and amiodarone in the European Myocardial Infarction Amiodarone Trial (EMIAT)  and the Canadian Amiodarone Myocardial Infarction Arrhythmia Trial (CAMIAT) . A significant contributing factor to the failures in many of these clinical trials was patient selection. A broad net of patients were enrolled in these studies; even those at low risk for arrhythmic death were included and thus subjected to the potentially adverse effects of these agents. This resulted in antiarrhythmic therapy in a subset of patients in whom no benefit could be gained by exposure to the drug and, in many cases, in whom there was an increased risk of mortality due to drug-related arrhythmogenicity or nonarrhythmic toxicity.
KeywordsHeart Rate Variability Left Ventricular Ejection Fraction Sudden Cardiac Death Antiarrhythmic Agent Arrhythmic Death
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