Left Atrial Appendage Closure or Medical Therapy in Atrial Fibrillation.

The effectiveness of this strategy, as compared with physician-directed best medical care, in patients at high risk for stroke and bleeding is unknown.

与医生指导的最佳医疗护理相比，这种策略在高风险中风和出血患者中的有效性尚不明确。

Methods

In this multicenter randomized trial conducted in Germany, we assigned patients with atrial fibrillation and a high risk of stroke and bleeding to undergo left atrial appendage closure or to receive physician-directed best medical care (including direct oral anticoagulants, if eligible).

在这项在德国开展的多中心随机试验中，我们将房颤伴有高中风和出血风险的患者随机分配接受左心耳封堵术或接受医生指导的最佳医疗护理（包括符合条件的直接口服抗凝药物）。

The primary end point, tested for noninferiority, was a composite of stroke (ischemic or hemorrhagic), systemic embolism, major bleeding, or cardiovascular or unexplained death, assessed in a time-to-event analysis.

主要终点，用于测试非劣效性，是一个复合终点，包括中风（缺血性或出血性）、全身性栓塞、主要出血或心血管或不明原因死亡，通过时间至事件分析进行评估。

The noninferiority margin was a hazard ratioof 1.3.

非劣效边界是一个风险比为1.3。

Results

A total of 912 adult patients underwent randomization.

共有912名成年患者进行了随机分组。

The primary end-point analysis included 446 patients who were assigned to undergo left atrial appendage closure (device group) and 442 who were assigned to physician-directed best medical care (medical-therapy group).

主要终点分析包括了446名被分配进行左心耳封堵术（装置组）的患者和442名被分配进行医生指导的最佳药物治疗（药物治疗组）的患者。

The mean (±SD) age was 77.9±7.1 years; 38.6% of the patients were women, the mean CHA2DS2-VASc score was 5.2±1.5 (range, 0 to 9, with higher scores indicating a greater risk of stroke), and the mean HAS-BLED score was 3.0±0.9 (range, 0 to 9, with higher scores indicating higher risk of bleeding).

平均（±标准差）年龄为77.9±7.1岁；38.6%的患者为女性，平均CHA2DS2-VASc评分为5.2±1.5（范围，0至9，评分越高表示中风风险越大），平均HAS-BLED评分为3.0±0.9（范围，0至9，评分越高表示出血风险越高）。

After a median follow-up of 3 years (interquartile range, 1.7 to 4.7), a first primary end-point event had occurred in 155 patients (incidenceper 100 patient-years, 16.8) in the device group and in 127 patients (incidenceper 100 patient-years, 13.3) in the medical-therapy group (difference in restricted mean survival time, -0.36 years; 95% confidence interval, -0.70 to -0.01; P = 0.44 for noninferiority).

中位随访时间为3年（四分位数范围，1.7至4.7年），设备组有155名患者（每100患者年发生率，16.8）和医学治疗组有127名患者（每100患者年发生率，13.3）发生了首次主要终点事件（限制性平均生存时间差异，-0.36年；95%置信区间，-0.70至-0.01；P=0.44，用于非劣效性测试）。

Serious adverse events occurred in 368 patients (82.5%) in the device group and 342 (77.4%) in the medical-therapy group.

设备组中有368名患者（82.5%）和医学治疗组中有342名患者（77.4%）发生了严重不良事件。

Conclusions

Among patients with atrial fibrillation at high risk for stroke and bleeding, left atrial appendage closure was not noninferior to physician-directed best medical care with regard to a composite end point of stroke, systemic embolism, major bleeding, or cardiovascular or unexplained death.

在具有高中风和出血风险的房颤患者中，左心耳封堵术与医生指导的最佳医疗护理相比，在中风、全身性栓塞、主要出血或心血管或不明原因死亡的复合终点方面，并未显示出非劣效性。

(Funded by the German Center for Cardiovascular Research; CLOSURE-AF ClinicalTrials.gov number, NCT03463317.).

(由德国心血管研究中心资助; CLOSURE-AF ClinicalTrials.gov编号, NCT03463317.)