Dronedarone for maintenance of sinus rhythm in atrial fibrillation or flutter

　　背景：胺碘酮可有效维持房颤的窦性心律，但是有潜在的药物毒性反应。决奈达隆（Dronedarone）是一种新型的抗心律失常药物，药理作用与胺碘酮相似，但是发生副作用危险降低。

　　方法：两项同一、多中心、双盲、随机、对照研究，一项在欧洲（ClinicalTrials.gov number， NCT00259428），另一项在美国、加拿大、澳大利亚、南非和阿根廷（ClinicalTrials.gov number ，NCT00259376）。该研究评估了决奈达隆的有效性，其中828例患者接受决奈达隆治疗（400mg/次，2次/d），其余409例患者接受安慰剂。于2天、3天、5天、3个月、5个月、7个月、10个月、心律失常复发进行电话传输、远程心电监测及12个月内预定的随访时监测心律。

　　结果：欧洲研究组的结果显示心律失常复发的中位时间在安慰剂组和决奈达隆组分别为41d和96d（P=0.01），在非欧洲研究组分别为59d和158 d（P=0.002）。欧洲研究组复发心律失常患者的平均心室率在安慰剂组和决奈达隆组分别为117.5 ± 29.1次/m和102.3 ± 24.7次/m（P<0.001），非欧洲研究组分别为116.6 ± 31.9 次/m和104.6 ± 27.1次/m（P<0.001）。决奈达隆组的肺毒性反应、甲状腺和肝功能异常的发生率没有明显差异。

　　结论：决奈达隆与安慰剂相比可有效维持窦性心律，并可降低心律失常复发时的心室率。

　　（摘译自 新英格兰医学杂志 Volume 357:987-999）

Dronedarone for maintenance of sinus rhythm in atrial fibrillation or flutter.

BACKGROUND: Amiodarone is effective in maintaining sinus rhythm in atrial fibrillation but is associated with potentially serious toxic effects. Dronedarone is a new antiarrhythmic agent pharmacologically related to amiodarone but developed to reduce the risk of side effects.

METHODS: In two identical multicenter, double-blind, randomized trials, one conducted in Europe (ClinicalTrials.gov number, NCT00259428 [ClinicalTrials.gov] ) and one conducted in the United States, Canada, Australia, South Africa, and Argentina (termed the non-European trial, NCT00259376 [ClinicalTrials.gov] ), we evaluated the efficacy of dronedarone, with 828 patients receiving 400 mg of the drug twice daily and 409 patients receiving placebo. Rhythm was monitored transtelephonically on days 2, 3, and 5; at 3, 5, 7, and 10 months; during recurrence of arrhythmia; and at nine scheduled visits during a 12-month period. The primary end point was the time to the first recurrence of atrial fibrillation or flutter.

RESULTS: In the European trial, the median times to the recurrence of arrhythmia were 41 days in the placebo group and 96 days in the dronedarone group (P=0.01). The corresponding durations in the non-European trial were 59 and 158 days (P=0.002). At the recurrence of arrhythmia in the European trial, the mean (+/-SD) ventricular rate was 117.5+/-29.1 beats per minute in the placebo group and 102.3+/-24.7 beats per minute in the dronedarone group (P<0.001); the corresponding rates in the non-European trial were 116.6+/-31.9 and 104.6+/-27.1 beats per minute (P<0.001). Rates of pulmonary toxic effects and of thyroid and liver dysfunction were not significantly increased in the dronedarone group.

CONCLUSIONS: Dronedarone was significantly more effective than placebo in maintaining sinus rhythm and in reducing the ventricular rate during recurrence of arrhythmia. Copyright 2007 Massachusetts Medical Society.