Short-term versus long-term antiarrhythmic drug treatment after cardioversion of atrial fibrillation (Flec-SL): a prospective, randomised, open-label, blinded endpoint assessment trial
Short-term versus long-term antiarrhythmic drug treatment after cardioversion of atrial fibrillation (Flec-SL): a prospective, randomised, open-label, blinded endpoint assessment trial
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DOI：
10.1016/s0140-6736(12)60570-4
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发表时间：
2012-07-21
期刊：
影响因子：
168.9
通讯作者：
Breithardt, Guenter
中科院分区：
文献类型：
--
作者：
Kirchhof, Paulus;Andresen, Dietrich;Breithardt, Guenter
抗心律失常药物可延长心房肌动作电位和不应期，从而预防复律后房颤的复发。心房动作电位在窦性心律2-4周后恢复正常，这表明在此期间可能不需要抗心律失常药物。因此，我们调查心脏复律后短期抗心律失常药物治疗是否非劣效于长期treatment.Methods我们招募患者在2007年5月4日和2010年3月12日之间，在44个中心在德国的前瞻性，随机，开放标签，盲法终点评估试验。合格患者为接受计划心脏复律的持续性房颤成人患者。成功复律后，患者被随机分配到每个中心6个排列区组：无抗心律失常药物治疗（对照）;氟卡尼治疗（200-300 mg/天）4周（短期治疗）;或氟卡尼6个月（长期治疗）。主要终点是至持续性房颤或死亡的时间。患者和临床医生对分组和治疗揭盲。在核心实验室评估主要结局，其中成员对治疗组设盲。通过每日遥测心电图（ECG）和中心裁定的霍尔特ECG记录（无论何时在两次连续ECG中观察到房颤）对患者进行6个月的监测。分析符合方案。该试验已注册，编号为ISRCTN 62728742。研究结果在通过242例患者的4周随访数据建立检测灵敏度后，显示氟卡尼上级未治疗（Kaplan-Meier生存率为70.2% vs 52.5%; p=0.0160），该试验继续比较短期与长期治疗。261例接受短期治疗的患者中有120例（46%）发生主要结局，263例接受长期治疗的患者中有103例（39%）发生主要结局（无事件生存期48.4% [95% CI 41.9-55.0] vs 56.4% [49.1-63.6]; Kaplan-Meier差异估计值7.9% [-1.9至17.7];非劣效性p=0.2081;预设定的利润率为12%）。在对第一个月未达到主要终点的患者进行的事后里程碑分析中，长期治疗上级短期治疗（Kaplan-Meier差异估计值为14.3% [5.1-23.6];风险比为0.31 [0.18-0.56];解释心脏复律后短期抗心律失常药物治疗不如长期治疗有效，但可以预防大多数房颤复发。
Background Antiarrhythmic drugs prolong the atrial action potential and refractory period, and thereby prevent recurrent atrial fibrillation after cardioversion. The atrial action potential normalises after 2-4 weeks of sinus rhythm, suggesting that antiarrhythmic drugs might not be needed beyond that period. Therefore, we investigated whether short-term antiarrhythmic drug treatment after cardioversion is non-inferior to long-term treatment.Methods We enrolled patients in a prospective, randomised, open-label, blinded endpoint assessment trial between May 4, 2007, and March 12, 2010, at 44 centres in Germany. Eligible patients were adults with persistent atrial fibrillation undergoing planned cardioversion. After successful cardioversion, patients were randomly assigned in permuted blocks of six per centre to: no antiarrhythmic drug treatment (control); treatment with flecainide (200-300 mg per day) for 4 weeks (short-term treatment); or flecainide for 6 months (long-term treatment). The primary endpoint was time to persistent atrial fibrillation or death. Patients and clinicians were unmasked to group assignment and treatment. The primary outcome was assessed in a core laboratory, members of which were masked to treatment group. Patients were monitored for 6 months by daily telemetric electrocardiograph (ECG) and centrally adjudicated Holter ECG recordings whenever atrial fibrillation was noted in two consecutive ECGs. Analyses were per protocol. This trial is registered, number ISRCTN62728742.Findings After assay sensitivity was established with 4-week follow-up data from 242 patients showing that flecainide was superior to no treatment (Kaplan-Meier survival 70.2% vs 52.5%; p=0.0160), the trial continued to compare short-term versus long-term treatment. The primary outcome occurred in 120 (46%) of 261 patients receiving short-term treatment and in 103 (39%) of 263 patients receiving long-term treatment (event-free survival 48.4% [95% CI 41.9-55.0] vs 56.4% [49.1-63.6]; Kaplan-Meier estimate of difference 7.9% [-1.9 to 17.7]; p=0.2081 for non-inferiority; margin prespecified at 12%). In a post-hoc landmark analysis of patients who had not reached the primary endpoint in the first month, long-term treatment was superior to short-term treatment (Kaplan-Meier estimate of difference 14.3% [5.1-23.6]; hazard ratio 0.31 [0.18-0.56]; p=0.0001).Interpretation Short-term antiarrhythmic drug treatment after cardioversion is less effective than is long-term treatment, but can prevent most recurrences of atrial fibrillation.