Mount Sinai School of Medicine, New York City, New York2St John's Health Center, Santa Monica, California3Homolka Hospital, Prague, Czech Republic.
Cardiovascular Center Frankfurt, Sankt Katharinen, Frankfurt, Germany.
JAMA. 2014 Nov 19;312(19):1988-98. doi: 10.1001/jama.2014.15192.
While effective in preventing stroke in patients with atrial fibrillation (AF), warfarin is limited by a narrow therapeutic profile, a need for lifelong coagulation monitoring, and multiple drug and diet interactions.
To determine whether a local strategy of mechanical left atrial appendage (LAA) closure was noninferior to warfarin.
DESIGN, SETTING, AND PARTICIPANTS: PROTECT AF was a multicenter, randomized (2:1), unblinded, Bayesian-designed study conducted at 59 hospitals of 707 patients with nonvalvular AF and at least 1 additional stroke risk factor (CHADS2 score ≥1). Enrollment occurred between February 2005 and June 2008 and included 4-year follow-up through October 2012. Noninferiority required a posterior probability greater than 97.5% and superiority a probability of 95% or greater; the noninferiority margin was a rate ratio of 2.0 comparing event rates between treatment groups.
Left atrial appendage closure with the device (n = 463) or warfarin (n = 244; target international normalized ratio, 2-3).
A composite efficacy end point including stroke, systemic embolism, and cardiovascular/unexplained death, analyzed by intention-to-treat.
At a mean (SD) follow-up of 3.8 (1.7) years (2621 patient-years), there were 39 events among 463 patients (8.4%) in the device group for a primary event rate of 2.3 events per 100 patient-years, compared with 34 events among 244 patients (13.9%) for a primary event rate of 3.8 events per 100 patient-years with warfarin (rate ratio, 0.60; 95% credible interval, 0.41-1.05), meeting prespecified criteria for both noninferiority (posterior probability, >99.9%) and superiority (posterior probability, 96.0%). Patients in the device group demonstrated lower rates of both cardiovascular mortality (1.0 events per 100 patient-years for the device group [17/463 patients, 3.7%] vs 2.4 events per 100 patient-years with warfarin [22/244 patients, 9.0%]; hazard ratio [HR], 0.40; 95% CI, 0.21-0.75; P = .005) and all-cause mortality (3.2 events per 100 patient-years for the device group [57/466 patients, 12.3%] vs 4.8 events per 100 patient-years with warfarin [44/244 patients, 18.0%]; HR, 0.66; 95% CI, 0.45-0.98; P = .04).
After 3.8 years of follow-up among patients with nonvalvular AF at elevated risk for stroke, percutaneous LAA closure met criteria for both noninferiority and superiority, compared with warfarin, for preventing the combined outcome of stroke, systemic embolism, and cardiovascular death, as well as superiority for cardiovascular and all-cause mortality.
clinicaltrials.gov Identifier: NCT00129545.
虽然在预防心房颤动（AF）患者的中风方面有效，但华法林的疗效有限，治疗范围狭窄，需要终生进行凝血监测，并且存在多种药物和饮食相互作用。
确定局部机械左心耳（LAA）闭合策略是否不劣于华法林。
设计、地点和参与者：PROTECT AF 是一项多中心、随机（2:1）、非盲、贝叶斯设计的研究，在 707 名非瓣膜性 AF 且至少有 1 个额外中风危险因素（CHADS2 评分≥1）的患者中，在 59 家医院进行。招募发生在 2005 年 2 月至 2008 年 6 月之间，并在 2012 年 10 月之前进行了为期 4 年的随访。非劣效性需要后验概率大于 97.5%，而优越性需要概率大于 95%或更大；非劣效性边界为两组之间事件发生率的比率为 2.0。
使用设备（n=463）或华法林（n=244；目标国际标准化比值为 2-3）进行左心耳闭合。
通过意向治疗分析，包括中风、全身性栓塞和心血管/不明原因死亡在内的复合疗效终点。
在平均（SD）随访 3.8（1.7）年（2621 患者年）期间，在设备组的 463 名患者中，有 39 名患者（8.4%）发生了主要事件，主要事件发生率为每 100 患者年 2.3 例，而在 244 名患者中的 34 名患者（13.9%）中，每 100 患者年发生主要事件的发生率为 3.8 例，华法林的发生率为 0.60（95%可信区间，0.41-1.05），符合非劣效性（后验概率，>99.9%）和优越性（后验概率，96.0%）的预设标准。设备组患者的心血管死亡率较低（设备组每 100 患者年发生 1.0 例[463 例患者中有 17 例，3.7%]，华法林组每 100 患者年发生 2.4 例[244 例患者中有 22 例，9.0%]；危险比[HR]，0.40；95%CI，0.21-0.75；P=0.005）和全因死亡率（设备组每 100 患者年发生 3.2 例[466 例患者中有 57 例，12.3%]，华法林组每 100 患者年发生 4.8 例[244 例患者中有 44 例，18.0%]；HR，0.66；95%CI，0.45-0.98；P=0.04）。
在非瓣膜性 AF 且中风风险升高的患者中，经过 3.8 年的随访，与华法林相比，经皮 LAA 闭合在预防中风、全身性栓塞和心血管死亡的联合结局方面具有非劣效性和优越性，在心血管和全因死亡率方面具有优越性。
clinicaltrials.gov 标识符：NCT00129545。
