O'Callaghan P A, McGovern B A
Cardiac Arrhythmia Services, Massachusetts General Hospital, Boston 02114, USA.
Am J Cardiol. 1996 Aug 29;78(4A):54-60. doi: 10.1016/s0002-9149(96)00453-5.
Sotalol is a unique compound with several potential antiarrhythmic mechanisms, including beta blockade (class II activity), action potential duration prolongation (class III activity), and possibly reduction of QT dispersion. In recent years, trials such as the Cardiac Arrhythmia Suppression Trial (CAST) and the Electrophysiologic Study versus Electrocardiographic Monitoring (ESVEM) trial reported disappointing results with the use of class I agents in the management of ventricular arrhythmias in patients with coronary artery disease. These results have led to increased interest in class III antiarrhythmic agents, including sotalol. Sotalol is effective in suppressing ventricular premature complexes as well as nonsustained and sustained ventricular tachyarrhythmias. The interaction between sotalol and implantable cardioverter-defibrillators (ICDs) is generally favorable. As is the case with other antiarrhythmic drugs, there is no placebo-controlled trial assessing the effect of sotalol on mortality. It is not known if sotalol is more effective than placebo, conventional beta blockade, amiodarone, or ICDs in reducing mortality from life-threatening ventricular arrhythmias. In addition, the optimal method of selecting patients for sotalol therapy has yet to be determined. The safety profile of sotalol has been well established in > 3,000 patients worldwide. Proarrhythmia occurs in approximately 4% of patients, and torsades de pointes occurs in approximately 2.5%. The majority of episodes of torsades de pointes occurs within 3 days of commencing sotalol therapy, and the risk of torsades de pointes increases sharply at dosages > 320 mg daily. It is recommended that initiation of sotalol therapy or dosage increases be performed in a monitored setting. Overall, only 1% of patients enrolled in clinical trials of sotalol discontinued therapy as a result of drug-related congestive heart failure. However, these trials have excluded patients with poor left ventricular systolic function and/or overt heart failure. The optimal management of these patients, who are at greatest risk of sudden cardiac death, and of patients with substrates other than coronary artery disease remains to be elucidated.
索他洛尔是一种具有多种潜在抗心律失常机制的独特化合物，包括β受体阻滞（II类活性）、动作电位时程延长（III类活性），以及可能减少QT离散度。近年来，诸如心律失常抑制试验（CAST）和电生理研究与心电图监测（ESVEM）试验等研究报告了在冠状动脉疾病患者中使用I类药物治疗室性心律失常的结果令人失望。这些结果使得人们对包括索他洛尔在内的III类抗心律失常药物的兴趣增加。索他洛尔在抑制室性早搏以及非持续性和持续性室性快速心律失常方面有效。索他洛尔与植入式心脏复律除颤器（ICD）之间的相互作用总体上是有利的。与其他抗心律失常药物一样，尚无安慰剂对照试验评估索他洛尔对死亡率的影响。尚不清楚索他洛尔在降低危及生命的室性心律失常导致的死亡率方面是否比安慰剂、传统β受体阻滞剂、胺碘酮或ICD更有效。此外，选择索他洛尔治疗患者的最佳方法尚未确定。索他洛尔的安全性在全球3000多名患者中已得到充分证实。致心律失常作用发生在约4%的患者中，尖端扭转型室速发生在约2.5%的患者中。大多数尖端扭转型室速发作发生在开始索他洛尔治疗的3天内，且每日剂量>320mg时尖端扭转型室速的风险急剧增加。建议在监测环境下开始索他洛尔治疗或增加剂量。总体而言，在索他洛尔临床试验中，只有1%的患者因药物相关的充血性心力衰竭而停药。然而，这些试验排除了左心室收缩功能差和/或明显心力衰竭的患者。对于这些心脏性猝死风险最高的患者以及患有冠状动脉疾病以外其他疾病的患者的最佳管理方法仍有待阐明。
