英国伦敦大学学院David J Werring团队研究了缺血性卒中和房颤后抗凝最佳时机。该项研究成果发表在2025年6月23日出版的《柳叶刀》上。

口服抗凝剂预防急性缺血性卒中合并心房颤动患者早期缺血性卒中复发的最佳时机仍不确定。该研究旨在评估在缺血性卒中发作后早期（≤4天）与晚期（≥5天）开始直接口服抗凝剂（DOAC）的效果。

在这项系统评价和荟萃分析中，研究组检索了PubMed、Cochrane中央对照试验注册库和Embase等电子数据库，筛选从研究开始到2025年3月16日发表的随机对照试验。研究组纳入了预先注册、随机化、临床结果调查的临床试验，并纳入了急性缺血性卒中和房颤患者，他们被分配到批准剂量的DOAC的早期或较晚起始（≤4天vs≥5天）。主要结局是随机分组后30天内复发性缺血性卒中、症状性脑出血或未分类卒中的综合结局。次要结局包括30天和90天内的主要综合结局。研究组使用广义线性混合效应模型进行了一期个体患者数据荟萃分析，考虑了试验间差异，以比值比（OR）和95%CI表示治疗效果。本研究已注册为PROSPERO， CRD42024522634。

研究组确定了4个符合条件的试验：TIMING （NCT02961348）、ELAN （NCT03148457）、OPTIMAS （NCT03759938）和START （NCT03021928）。在排除了选择退出数据共享或在4天内、第5天或之后没有被随机分配到DOAC起始的参与者后，研究人员在个体患者数据荟萃分析中纳入了5441名参与者（平均年龄77.7岁[SD 10.0]， 2472名[45.4%]女性，中位数为美国国立卫生研究院卒中量表5 [IQR 3-10]）。研究团队获得了5429名参与者的主要结局数据。

2683名早期开始DOAC治疗的受试者中有57人（2.1%）出现主要结局，而2746名较晚开始DOAC治疗的受试者中有83人（3.0%）出现主要结局（OR 0.70, 95% CI 0.50 - 0.98, p= 0.039）。早期DOAC降低了缺血性卒中复发的风险（2683例中45例[1.7%]vs 2746例中70例[2.6%]，OR为0.66,0.45 - 0.96，p= 0.029）。没有证据表明早期DOAC启动会增加症状性脑出血（2683例10例[0.4%]vs 2746例10例[0.4%]，OR为0.02,0.43 - 2 - 0.46，p= 0.96）。

研究结果支持在临床实践中尽早启动DOAC，对于急性缺血性卒中和房颤患者，早期（4天内）开始DOAC可降低30天内复发性缺血性卒中、症状性脑出血或未分类卒中的复合结局的风险。

附：英文原文

Title: Collaboration on the optimal timing of anticoagulation after ischaemic stroke and atrial fibrillation: a systematic review and prospective individual participant data meta-analysis of randomised controlled trials (CATALYST)

Author: Hakim-Moulay Dehbi, Urs Fischer, Signild sberg, Truman J Milling, Stefanie Abend, Norin Ahmed, Mattia Branca, Lisa A Davis, Stefan T Engelter, Nick Freemantle, Thomas Gattringer, Tatevik Ghukasyan Lakic, Ziad Hijazi, Martin James, Masatoshi Koga, Patrick Lawrence, Robin Lemmens, Gregory Y H Lip, Susan Massingham, Philip S Nash, Amalia Ndoutoumou, Bo Norrving, Georgia Salanti, Nikola Sprigg, Gtz Thomalla, Tishok Vanniyasingam, Per Wester, Steven J Warach, Jonas Oldgren, Jesse Dawson, David J Werring

Issue&Volume: 2025-06-23

Abstract:

Background

The optimal timing of oral anticoagulation for prevention of early ischaemic stroke recurrence in people with acute ischaemic stroke and atrial fibrillation remains uncertain. We aimed to estimate the effects of starting a direct oral anticoagulant (DOAC) early (≤4 days) versus later (≥5 days) after onset of ischaemic stroke.

Methods

For this systematic review and meta-analysis we searched the electronic databases PubMed, Cochrane Central Register of Controlled Trials, and Embase for randomised controlled trials published from inception until March 16, 2025. We included clinical trials if they were pre-registered, randomised, investigated clinical outcomes, and included participants with acute ischaemic stroke and atrial fibrillation who were assigned to either early or later initiation (≤4 days vs ≥5 days) of a DOAC in approved doses. The primary outcome was a composite of recurrent ischaemic stroke, symptomatic intracerebral haemorrhage, or unclassified stroke within 30 days of randomisation. Secondary outcomes included components of the primary composite within 30 days and 90 days. We did a one-stage individual patient data meta-analysis with the use of a generalised linear mixed-effects model, accounting for between-trial differences, to generate treatment effects, which are presented as odds ratios (ORs) and 95% CIs. This study is registered with PROSPERO, CRD42024522634.

Findings

We identified four eligible trials: TIMING (NCT02961348), ELAN (NCT03148457), OPTIMAS (NCT03759938), and START (NCT03021928). After excluding participants who opted out of data sharing or were not randomly assigned to DOAC initiation within 4 days or at day 5 or later, we included 5441 participants (mean age 77·7 years [SD 10·0], 2472 [45·4%] women, median National Institutes of Health Stroke Scale 5 [IQR 3–10]) in the individual patient data meta-analysis. We obtained primary outcome data for 5429 participants. The primary outcome occurred in 57 (2·1%) of 2683 participants who started DOAC early versus 83 (3·0%) of 2746 participants who started later (OR 0·70, 95% CI 0·50–0·98, p=0·039). Early DOAC reduced the risk of recurrent ischaemic stroke (45 [1·7%] of 2683 vs 70 [2·6%] of 2746, OR 0·66, 0·45–0·96, p=0·029). There was no evidence of an increase in symptomatic intracerebral haemorrhage with early DOAC initiation (10 [0·4%] of 2683 vs 10 [0·4%] of 2746, OR 1·02, 0·43–2·46, p=0·96).

Interpretation

For people with acute ischaemic stroke and atrial fibrillation, early DOAC initiation (within 4 days) reduced the risk of the composite outcome of recurrent ischaemic stroke, symptomatic intracerebral haemorrhage, or unclassified stroke within 30 days. These findings support early DOAC initiation in clinical practice.

DOI: 10.1016/S0140-6736(25)00439-8

Source: https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(25)00439-8/abstract