Department of Cardiology and Angiology, Hospital of the University of Münster, Germany.
Lancet. 2012 Jul 21;380(9838):238-46. doi: 10.1016/S0140-6736(12)60570-4. Epub 2012 Jun 18.
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.
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.
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).
Short-term antiarrhythmic drug treatment after cardioversion is less effective than is long-term treatment, but can prevent most recurrences of atrial fibrillation.
The German Federal Ministry of Education and Research, Deutsche Forschungsgemeinschaft, 3M Medica, and MEDA Pharmaceuticals.
抗心律失常药物可延长心房动作电位和不应期，从而防止电复律后心房颤动复发。窦性心律恢复 2-4 周后心房动作电位恢复正常，这表明在该时间段之后可能不需要抗心律失常药物。因此，我们研究了电复律后短期抗心律失常药物治疗是否不如长期治疗。
我们在 2007 年 5 月 4 日至 2010 年 3 月 12 日期间在德国的 44 个中心进行了一项前瞻性、随机、开放标签、盲终点评估试验，纳入了计划接受电复律的持续性心房颤动的成年患者。电复律成功后，患者按中心区组（每组 6 例）随机分配至：无抗心律失常药物治疗（对照组）；用氟卡尼（每天 200-300mg）治疗 4 周（短期治疗）；或氟卡尼治疗 6 个月（长期治疗）。主要终点是持续性心房颤动或死亡的时间。患者和临床医生对分组和治疗方案均不知情。主要结局由核心实验室评估，核心实验室成员对治疗组不知情。通过每天的远程心电图（ECG）和中央裁定的动态心电图记录监测患者 6 个月，每当连续两次 ECG 记录到心房颤动时，就会进行监测。分析采用方案规定的方法。该试验在 ISRCTN 注册，编号为 ISRCTN62728742。
在对 242 例患者进行了 4 周随访的检测灵敏度建立后（结果显示氟卡尼治疗优于无治疗[Kaplan-Meier 生存 70.2%vs 52.5%；p=0.0160]），试验继续比较短期治疗与长期治疗。在接受短期治疗的 261 例患者中，120 例（46%）和接受长期治疗的 263 例患者中 103 例（39%）发生主要结局（无事件生存 48.4%[95%CI 41.9-55.0]vs 56.4%[49.1-63.6]；Kaplan-Meier 估计差值 7.9%[-1.9 至 17.7]；p=0.2081 用于非劣效性；预设边界为 12%）。在第一个月未达到主要终点的患者的事后里程碑分析中，长期治疗优于短期治疗（Kaplan-Meier 估计差值 14.3%[5.1-23.6]；风险比 0.31[0.18-0.56]；p=0.0001）。
电复律后短期抗心律失常药物治疗不如长期治疗有效，但可以预防大多数心房颤动的复发。
德国联邦教育与研究部、德国研究基金会、3M Medica 和 MEDA 制药公司。
