Camm A J, Karam R, Pratt C M
Department of Cardiological Sciences, St. George's Hospital Medical School, London, United Kingdom.
Am J Cardiol. 1998 Mar 19;81(6A):35D-39D. doi: 10.1016/s0002-9149(98)00151-9.
The AzimiLide post-Infarct surVival Evaluation (ALIVE) trial is a new clinical trial using an innovative design to examine the potential of azimilide, a novel type of antiarrhythmic, for improving survival in post myocardial infarction (MI) patients at high risk of sudden cardiac death. Azimilide is the first of a unique class of antiarrhythmic drugs that blocks both slow and rapid components of the delayed rectifier potassium currents in human myocardium. Preclinical studies have shown the drug to be effective in reducing cardiac tachyarrhythmias, even under ischemic conditions. Currently, azimilide is in Phase III trials for the treatment of supraventricular arrhythmias. The ALIVE study design is based on lessons learned from the Cardiac Arrhythmia Suppression Trials (CAST), the Survival With Oral d-Sotalol (SWORD) trial, and the European Myocardial Infarction Amiodarone Trial (EMIAT) and identifies recent post-MI patients at high risk of sudden cardiac death. The hypothesis underlying this trial is that azimilide will improve survival in this patient population. The ALIVE trial is designed as a double-blind, placebo-controlled, multinational trial that will overcome the shortcomings of previous antiarrhythmic trials by using left ventricular ejection fraction and heart rate variability as predictors to target a post-MI patient population at high risk of sudden death. The major inclusion criteria for the study are adult patients of either gender with a left ventricular ejection fraction of 15-35% who have had a recent MI (within 6-21 days). Additional stratification will be based on patients with heart rate variability < or = 20 U (heart rate variability index). Exclusion criteria include factors that may predispose a patient to nonarrhythmia-induced death or to low risk of sudden cardiac death caused by arrhythmia. Sample size is based on the assumption that the all-cause mortality rate (the primary endpoint) for 1 year in placebo patients at high risk for sudden cardiac death (heart rate variability < or = 20 U) is 15% and that azimilide will decrease all-cause mortality by at least 45% in these patients. The trial consists of 3 groups-patients receiving 75 mg azimilide orally each day, patients receiving 100 mg azimilide orally each day, and patients receiving placebo. No dose adjustments for age, gender, renal or hepatic failure, or concomitant use of warfarin or digoxin are thought necessary with azimilide. Enrollment for the trial is expected to continue for 24 months, and treatment is scheduled to be administered for a 1-year follow-up period.
阿齐米利德心肌梗死后生存评估（ALIVE）试验是一项新的临床试验，采用创新设计来研究新型抗心律失常药物阿齐米利德在改善心肌梗死（MI）后有心脏性猝死高风险患者生存率方面的潜力。阿齐米利德是一类独特的抗心律失常药物中的首个药物，它可阻断人心肌中延迟整流钾电流的慢速和快速成分。临床前研究表明，该药物即使在缺血条件下也能有效减少心脏快速性心律失常。目前，阿齐米利德正处于治疗室上性心律失常的III期试验阶段。ALIVE研究设计借鉴了心律失常抑制试验（CAST）、口服d - 索他洛尔生存试验（SWORD）以及欧洲心肌梗死胺碘酮试验（EMIAT）的经验教训，确定近期心肌梗死后有心脏性猝死高风险的患者。该试验的基本假设是阿齐米利德将改善这一患者群体的生存率。ALIVE试验设计为一项双盲、安慰剂对照的跨国试验，将通过使用左心室射血分数和心率变异性作为预测指标，针对有心脏性猝死高风险的心肌梗死后患者群体，克服以往抗心律失常试验的缺点。该研究的主要纳入标准是年龄在18岁及以上、左心室射血分数为15% - 35%且近期发生心肌梗死（6 - 21天内）的成年患者，无论性别。进一步分层将基于心率变异性≤20 U（心率变异性指数）的患者。排除标准包括可能使患者易患非心律失常性死亡或因心律失常导致心脏性猝死低风险的因素。样本量基于这样的假设：心脏性猝死高风险（心率变异性≤20 U）的安慰剂患者1年的全因死亡率（主要终点）为15%，而阿齐米利德将使这些患者的全因死亡率至少降低45%。该试验包括3组：每天口服75毫克阿齐米利德的患者、每天口服100毫克阿齐米利德的患者以及接受安慰剂的患者。对于阿齐米利德，无需根据年龄、性别、肾功能或肝功能衰竭，或华法林或地高辛的合并使用情况进行剂量调整。预计该试验的入组将持续24个月，治疗计划为期1年的随访期。
