Percutaneous closure of the left atrial appendage versus warfarin therapy for prevention of stroke in patients with atrial fibrillation: a randomised non-inferiority trial
Percutaneous closure of the left atrial appendage versus warfarin therapy for prevention of stroke in patients with atrial fibrillation: a randomised non-inferiority trial
复制标题
DOI：
10.1016/s0140-6736(09)61343-x
复制
发表时间：
2009-08-15
期刊：
影响因子：
168.9
通讯作者：
Sick, Peter
中科院分区：
文献类型：
--
作者：
Holmes, David R.;Reddy, Vivek Y.;Sick, Peter
背景：在非瓣膜性心房颤动患者中，栓塞性卒中被认为与左心房附件（LAA）血栓有关。我们评估了经皮关闭LAA与华法林治疗房颤患者预防卒中的有效性和安全性。方法成年非瓣膜性心房颤动患者如果至少有以下一项：既往中风或短暂性缺血性发作、充血性心力衰竭、糖尿病、高血压，或年龄在75岁或以上，则有资格纳入这项多中心随机非效性试验。通过计算机生成的随机化顺序，707名符合条件的患者以2:1的比例随机分配到经皮关闭LAA并随后停用华法林（干预，n=463）或华法林治疗，目标国际标准化比率在2.0至3.0之间（对照组，n=244）。通过卒中、心血管死亡和全身性栓塞的主要复合终点来评估疗效。通过使用两倍非劣效裕度，我们选择了至少97.5%的干预的单侧非劣效性概率标准。构成安全性主要终点的严重不良事件包括大出血、心包积液和器械栓塞。分析的目的是治疗。本研究已在Clinicaltrials.gov注册，注册号为NCT00129545。随访1065患者-年，干预组的主要疗效事件发生率为3.0 / 100患者-年（95%可信区间[CrI] 1.9-4.5），对照组为4.9 / 100患者-年（2.8-7.1）（比率比[RRI 0.62, 95% CrI 0.35-1.25）。干预的非劣效性概率大于99.9%。干预组的主要安全事件发生率高于对照组（7.4 / 100患者-年，95% CrI 5.5-9.7； 4.4 / 100患者-年，95% CrI 2.5-6.7; RR 1.69, 1.01-3.19）。该装置经皮缝合LAA的效果不逊于华法林治疗。虽然干预组的不良安全事件发生率高于对照组，但干预组的不良安全事件主要由围手术期并发症引起。关闭LAA可能为非瓣膜性房颤患者预防中风提供慢性华法林治疗的替代策略。资金Atritech。
Background In patients with non-valvular atrial fibrillation, embolic stroke is thought to be associated with left atrial appendage (LAA) thrombi. We assessed the efficacy and safety of percutaneous closure of the LAA for prevention of stroke compared with warfarin treatment in patients with atrial fibrillation.Methods Adult patients with non-valvular atrial fibrillation were eligible for inclusion in this multicentre, randomised non-inferiority trial if they had at least one of the following: previous stroke or transient ischaemic attack, congestive heart failure, diabetes, hypertension, or were 75 years or older. 707 eligible patients were randomly assigned in a 2:1 ratio by computer-generated randomisation sequence to percutaneous closure of the LAA and subsequent discontinuation of warfarin (intervention; n=463) or to warfarin treatment with a target international normalised ratio between 2.0 and 3.0 (control; n=244). Efficacy was assessed by a primary composite endpoint of stroke, cardiovascular death, and systemic embolism. We selected a one-sided probability criterion of non-inferiority for the intervention of at least 97.5%, by use of a two-fold non-inferiority margin. Serious adverse events that constituted the primary endpoint for safety included major bleeding, pericardial effusion, and device embolisation. Analysis was by intention to treat. This study is registered with Clinicaltrials.gov, number NCT00129545.Findings At 1065 patient-years of follow-up, the primary efficacy event rate was 3.0 per 100 patient-years (95% credible interval [CrI] 1.9-4.5) in the intervention group and 4.9 per 100 patient-years (2.8-7.1) in the control group (rate ratio [RRI 0.62, 95% CrI 0.35-1.25). The probability of non-inferiority of the intervention was more than 99.9%. Primary safety events were more frequent in the intervention group than in the control group (7.4 per 100 patient-years, 95% CrI 5.5-9.7, vs 4.4 per 100 patient-years, 95% CrI 2.5-6.7; RR 1.69, 1.01-3.19).Interpretation The efficacy of percutaneous closure of the LAA with this device was non-inferior to that of warfarin therapy. Although there was a higher rate of adverse safety events in the intervention group than in the control group, events in the intervention group were mainly a result of periprocedural complications. Closure of the LAA might provide an alternative strategy to chronic warfarin therapy for stroke prophylaxis in patients with non-valvular atrial fibrillation.Funding Atritech.