Marinheiro Gabriel, Araújo Beatriz, Rivera André, Monteiro Gabriel de Almeida, Santana Laís Silva, Leite Marianna, Mutarelli Antonio, Pinheiro Agostinho C, Figueiredo Eberval Gadelha, Telles João Paulo Mota
School of Medicine, Federal University of Ceará, Sobral, Ceará, Brazil.
Department of Medicine, Nove de Julho University, São Bernardo do Campo, Brazil.
J Thromb Thrombolysis. 2024 Oct;57(7):1163-1171. doi: 10.1007/s11239-024-03017-7. Epub 2024 Jul 29.
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; I = 0%), ischemic stroke or systemic embolism (RR 0.97; 95% CI 0.80-1.17; p = 0.72; I = 0%), ischemic stroke (RR 0.92; 95% CI 0.79-1.06; p = 0.23; I = 0%), and all-cause mortality (RR 1.11; 95% CI 0.87-1.42; p = 0.39; I = 0%). DOACs increased the risk of clinically relevant non-major bleeding (CRNB) (RR 1.52; 95% CI 1.20-1.93; p < 0.01; I = 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; I = 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; I = 0%), all-cause mortality (RR 1.24; 95% CI 0.58-2.66; p = 0.57; I = 0%), and major bleeding (RR 1.00, 95% CI 0.32-3.08; p = 1.00; I = 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.
直接口服抗凝剂（DOAC）在不明来源栓塞性卒中（ESUS）患者中的疗效和安全性仍不明确。我们系统检索了PubMed、Embase和Cochrane图书馆，以查找比较DOAC与阿司匹林治疗ESUS患者的随机对照试验（RCT）。计算二元终点的风险比（RR）和95%置信区间（CI）。纳入了四项包含13970例患者的RCT。与阿司匹林相比，DOAC在复发性卒中（RR 0.95；95%CI 0.84-1.09；p = 0.50；I = 0%）、缺血性卒中和全身性栓塞（RR 0.97；95%CI 0.80-1.17；p = 0.72；I = 0%）、缺血性卒中（RR 0.92；95%CI 0.79-1.06；p = 0.23；I = 0%）以及全因死亡率（RR 1.11；95%CI 0.87-1.42；p = 0.39；I = 0%）方面未显示出显著降低。与阿司匹林相比，DOAC增加了临床相关非大出血（CRNB）的风险（RR 1.52；95%CI 1.20-1.93；p < 0.01；I = 7%），而两组之间大出血无显著差异（RR 1.57；95%CI 0.87-2.83；p = 0.14；I = 63%）。在对非主要心源性栓塞风险因素患者的亚分析中，两组在复发性卒中（RR 0.98；95%CI 0.67-1.42；p = 0.90；I = 0%）、全因死亡率（RR 1.24；95%CI 0.58-2.66；p = 0.57；I = 0%）和大出血（RR 1.00，95%CI 0.32-3.08；p = 1.00；I = 0%）方面无差异。在ESUS患者中，DOAC并未降低复发性卒中、缺血性卒中和全身性栓塞或全因死亡率的风险。尽管临床相关非大出血显著增加，但DOAC与阿司匹林之间的大出血情况相似。
