Abstract：
The efficacy and safety of direct oral anticoagulants (DOAC) in patients with embolic stroke of undetermined source (ESUS) remains unclear. We systematically searched PubMed, Embase, and Cochrane Library for randomized controlled trials (RCT) comparing DOACs versus aspirin in patients with ESUS. Risk ratios (RR) and 95% confidence intervals (CI) were computed for binary endpoints. Four RCTs comprising 13,970 patients were included. Compared with aspirin, DOACs showed no significant reduction of recurrent stroke (RR 0.95; 95% CI 0.84-1.09; p = 0.50; I2 = 0%), ischemic stroke or systemic embolism (RR 0.97; 95% CI 0.80-1.17; p = 0.72; I2 = 0%), ischemic stroke (RR 0.92; 95% CI 0.79-1.06; p = 0.23; I2 = 0%), and all-cause mortality (RR 1.11; 95% CI 0.87-1.42; p = 0.39; I2 = 0%). DOACs increased the risk of clinically relevant non-major bleeding (CRNB) (RR 1.52; 95% CI 1.20-1.93; p < 0.01; I2 = 7%) compared with aspirin, while no significant difference was observed in major bleeding between groups (RR 1.57; 95% CI 0.87-2.83; p = 0.14; I2 = 63%). In a subanalysis of patients with non-major risk factors for cardioembolism, there is no difference in recurrent stroke (RR 0.98; 95% CI 0.67-1.42; p = 0.90; I2 = 0%), all-cause mortality (RR 1.24; 95% CI 0.58-2.66; p = 0.57; I2 = 0%), and major bleeding (RR 1.00, 95% CI 0.32-3.08; p = 1.00; I2 = 0%) between groups. In patients with ESUS, DOACs did not reduce the risk of recurrent stroke, ischemic stroke or systemic embolism, or all-cause mortality. Although there was a significant increase in clinically relevant non-major bleeding, major bleeding was similar between DOACs and aspirin.
摘要：
直接口服抗凝药（DOAC）在来源不明的栓塞性卒中（ESUS）患者中的疗效和安全性尚不清楚。我们系统地搜索了PubMed,Embase,和CochraneLibrary用于比较DOAC与阿司匹林在ESUS患者中的随机对照试验（RCT）。计算二元终点的风险比(RR)和95%置信区间(CI)。包括13,970名患者的四个RCT被包括在内。与阿司匹林相比，DOAC显示复发性卒中无显著减少(RR0.95;95%CI0.84-1.09;p=0.50;I2=0%),缺血性卒中或全身性栓塞(RR0.97;95%CI0.80-1.17;p=0.72;I2=0%),缺血性卒中(RR0.92;95%CI0.79-1.06;p=0.23;I2=0%)，和全因死亡率(RR1.11;95%CI0.87-1.42;p=0.39;I2=0%)。与阿司匹林相比，DOAC增加了临床相关非大出血（CRNB）的风险（RR1.52;95％CI1.20-1.93;p<0.01;I2=7％），而两组间大出血无显著差异(RR1.57;95%CI0.87-2.83;p=0.14;I2=63%)。在对心源性栓塞非主要危险因素患者的亚分析中，复发性卒中无差异(RR0.98;95%CI0.67-1.42;p=0.90;I2=0%),全因死亡率（RR1.24；95%CI0.58-2.66；p=0.57；I2=0%），和严重出血（RR1.00，95％CI0.32-3.08；p=1.00；I2=0％）。在ESUS患者中，DOAC并没有降低卒中复发的风险，缺血性中风或全身性栓塞，或全因死亡率。尽管临床相关的非大出血显著增加，DOACs和阿司匹林的大出血情况相似.
