Doval H C
Instituto del Corazon, Hospital Italiano, Buenos Aires, Argentina.
Am J Cardiol. 1999 Nov 4;84(9A):109R-114R. doi: 10.1016/s0002-9149(99)00711-0.
The results of previous clinical trials, in a variety of clinical settings, showed that class I agents may consistently increase mortality in sharp contrast to the effects of beta blockers. Attention has therefore shifted to class III compounds for potential beneficial effects on long-term mortality among patients with underlying cardiac disease. Clinical trials with d-sotalol, the dextro isomer (devoid of beta blockade) of sotalol, showed increased mortality in patients with low ejection fraction after myocardial infarction and in those with heart failure; whereas in the case of dofetilide, the impact on mortality was neutral. Because of the complex effects of its actions as an alpha-adrenergic blocker and a class III agent, the impact on mortality of amiodarone in patients with heart failure is of particular interest. A meta-analysis of 13 clinical trials revealed significant reductions in all-cause and cardiac mortality among patients with heart failure or previous myocardial infarction. Among these were 5 controlled clinical trials that investigated the effects of amiodarone on mortality among patients with heart failure. None of these trials was large relative to the beta-blocker trials in the postinfarction patients. However, the larger 2 of the 5 amiodarone trials produced discordant effects on mortality, neutral in one and significantly positive in the other. Some of the differences may be accounted for by the differences in eligibility criteria and baseline characteristics. Future trials that may be undertaken to resolve the discrepancies may need to allow for the newer findings on the effects of concomitant beta blockers, implantable devices, and possibly, spironolactone. All these modalities of treatment have been shown in controlled clinical trials to augment survival in patients with impaired ventricular function or manifest heart failure. Additional trials, some of which are currently in progress, compare amiodarone with implantable devices and other therapeutic interventions, and should help to clarify the optimal management strategy for patients with underlying heart failure.
以往在各种临床环境中进行的临床试验结果表明，与β受体阻滞剂的作用形成鲜明对比的是，I类药物可能会持续增加死亡率。因此，人们的注意力已转向III类化合物，以期对患有潜在心脏病的患者的长期死亡率产生潜在的有益影响。对索他洛尔的右旋异构体（无β受体阻滞作用）d-索他洛尔进行的临床试验表明，心肌梗死后射血分数低的患者以及心力衰竭患者的死亡率增加；而多非利特对死亡率的影响是中性的。由于胺碘酮作为α肾上腺素能阻滞剂和III类药物的作用具有复杂的效应，因此其对心力衰竭患者死亡率的影响尤其令人关注。一项对13项临床试验的荟萃分析显示，心力衰竭或既往心肌梗死患者的全因死亡率和心脏死亡率显著降低。其中有5项对照临床试验研究了胺碘酮对心力衰竭患者死亡率的影响。相对于心肌梗死后患者的β受体阻滞剂试验而言，这些试验规模均不大。然而，5项胺碘酮试验中规模较大的2项对死亡率产生了不一致的影响，一项为中性，另一项则显著为阳性。部分差异可能是由入选标准和基线特征的差异所致。未来为解决这些差异而可能开展的试验可能需要考虑到关于联合使用β受体阻滞剂、植入式装置以及可能的螺内酯的最新研究结果。在对照临床试验中已表明，所有这些治疗方式均可提高心室功能受损或明显心力衰竭患者的生存率。其他一些试验（其中一些目前正在进行中）将胺碘酮与植入式装置及其他治疗干预措施进行比较，这应有助于阐明潜在心力衰竭患者的最佳管理策略。
