BACKGROUND The PROTECT AF (WATCHMAN Left Atrial Appendage System for Embolic Protection in Patients With Atrial Fibrillation) trial demonstrated that left atrial appendage closure (LAAC) with the Watchman device (Boston Scientific, St. Paul, Minnesota) was equivalent to warfarin for preventing stroke in atrial fibrillation, but had a high rate of complications. In a second randomized trial, PREVAIL (Evaluation of the WATCHMAN LAA Closure Device in Patients With Atrial Fibrillation Versus Long Term Warfarin Therapy), the complication rate was low. The warfarin cohort experienced an unexpectedly low ischemic stroke rate, rendering the efficacy endpoints inconclusive. However, these outcomes were based on relatively few patients followed for a relatively short time. OBJECTIVES The final results of the PREVAIL trial, both alone and as part of a patient-level meta-analysis with the PROTECT AF trial, are reported with patients in both trials followed for 5 years. METHODS PREVAIL and PROTECT AF are prospective randomized clinical trials with patients randomized 2:1 to LAAC or warfarin; together, they enrolled 1,114 patients for 4,343 patient-years. Analyses are by intention-to-treat, and rates are events per 100 patient-years. RESULTS For the PREVAIL trial, the first composite coprimary endpoint of stroke, systemic embolism (SE), or cardiovascular/unexplained death did not achieve noninferiority (posterior probability for noninferiority = 88.4%), whereas the second coprimary endpoint of post-procedure ischemic stroke/SE did achieve noninferiority (posterior probability for noninferiority = 97.5%); the warfarin arm maintained an unusually low ischemic stroke rate (0.73%). In the meta-analysis, the composite endpoint was similar between groups (hazard ratio [HR]: 0.820; p = 0.27), as were all-stroke/SE (HR: 0.961; p = 0.87). The ischemic stroke/SE rate was numerically higher with LAAC, but this difference did not reach statistical significance (HR: 1.71; p = 0.080). However, differences in hemorrhagic stroke, disabling/fatal stroke, cardiovascular/unexplained death, all-cause death, and post-procedure bleeding favored LAAC (HR: 0.20; p = 0.0022; HR: 0.45; p = 0.03; HR: 0.59; p = 0.027; HR: 0.73; p = 0.035; HR: 0.48; p = 0.0003, respectively). CONCLUSIONS These 5-year outcomes of the PREVAIL trial, combined with the 5-year outcomes of the PROTECT AF trial, demonstrate that LAAC with Watchman provides stroke prevention in nonvalvular atrial fibrillation comparable to warfarin, with additional reductions in major bleeding, particularly hemorrhagic stroke, and mortality. (WATCHMAN Left Atrial Appendage System for Embolic Protection in Patients With Atrial Fibrillation; NCT00129545; and Evaluation of the WATCHMAN LAA Closure Device in Patients With Atrial Fibrillation Versus Long Term Warfarin Therapy; NCT01182441).

中文翻译：

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左心耳闭合后 5 年的结果

背景 PROTECT AF（用于房颤患者栓塞保护的 WATCHMAN 左心耳系统）试验表明，使用 Watchman 装置（Boston Scientific, St. Paul, Minnesota）进行左心耳封堵 (LAAC) 与预防中风的华法林等效心房颤动，但并发症发生率高。在第二项随机试验 PREVAIL（房颤患者与长期华法林治疗的 WATCHMAN LAA 闭合装置的评估）中，并发症发生率很低。华法林队列出现了出乎意料的低缺血性卒中率，导致疗效终点不确定。然而，这些结果是基于在相对较短的时间内随访的患者相对较少。目标 PREVAIL 试验的最终结果，无论是单独还是作为 PROTECT AF 试验患者水平荟萃分析的一部分，都报告了两项试验中的患者随访 5 年。方法 PREVAIL 和 PROTECT AF 是前瞻性随机临床试验，患者按 2:1 随机分配至 LAAC 或华法林；他们总共招募了 1,114 名患者，为期 4,343 患者年。分析是按意向治疗进行的，比率是每 100 患者年发生的事件。结果 对于 PREVAIL 试验，卒中、全身性栓塞 (SE) 或心血管/不明原因死亡的第一个复合共同主要终点未达到非劣效性（非劣效性的后验概率 = 88.4%），而第二个共同主要终点是术后缺血性卒中/SE 确实达到了非劣效性（非劣效性的后验概率 = 97.5%）；华法林组保持了异常低的缺血性卒中率 (0.73%)。在荟萃分析中，各组之间的复合终点相似（风险比 [HR]：0.820；p = 0.27），所有卒中/SE（HR：0.961；p = 0.87）也是如此。LAAC 的缺血性卒中/SE 发生率在数值上更高，但这种差异没有达到统计学显着性（HR：1.71；p = 0.080）。然而，出血性卒中、致残/致死性卒中、心血管/不明原因死亡、全因死亡和术后出血的差异有利于 LAAC（HR：0.20；p = 0.0022；HR：0.45；p = 0.03；HR：0.59； p = 0.027；HR：0.73；p = 0.035；HR：0.48；p = 0.0003，分别）。结论 PREVAIL 试验的这些 5 年结果，结合 PROTECT AF 试验的 5 年结果，证明具有 Watchman 的 LAAC 可提供与华法林相当的非瓣膜性房颤的卒中预防，并进一步减少大出血，尤其是出血性卒中和死亡率。（用于房颤患者栓塞保护的 WATCHMAN 左心耳系统；NCT00129545；以及评估房颤患者与长期华法林治疗相比的 WATCHMAN LAA 闭合装置；NCT01182441）。