Yu Hui-Tzu, Chen Kuan-Hsuan, Lin Chun-Jen, Hsu Chia-Chen, Chang Yuh-Lih
Department of Pharmacy, School of Pharmaceutical Sciences, National Yang Ming Chiao Tung University, Hsinchu City, Taiwan.
Department of Pharmacy, Taipei Veterans General Hospital, Taipei City, Taiwan.
Heliyon. 2023 Mar 11;9(3):e14456. doi: 10.1016/j.heliyon.2023.e14456. eCollection 2023 Mar.
Patients with atrial fibrillation (AF) are prescribed oral anticoagulants for stroke prevention; however, no evidence indicates that the use of direct oral anticoagulants (DOACs) in the first few days after ischemic stroke (IS) would result in favorable outcomes. This study evaluated the association between the timing of using DOACs after IS and their effectiveness and safety to determine the optimal timing.
In this retrospective cohort study, we reviewed the electronic medical records of Taipei Veterans General Hospital. The 1-year outcomes of patients after DOAC initiation were evaluated. Different initiation time windows were compared (initiation time ≤3 days and >3 days in primary analysis). The primary composite outcome was stroke, transient ischemic attack, systemic embolism, or death due to IS. The primary safety outcome was major bleeding or clinically relevant nonmajor bleeding. The secondary composite outcome was all-cause mortality, thromboembolic event, or acute myocardial infarction/hemorrhagic events.
This study included 570 patients. The median initiation time of DOACs after IS in the patients with AF was 14 days. Compared the patients in whom DOACs were initiated after >3 days with those DOACs were initiated after ≤3 days, the adjusted hazard ratios (aHRs) of the primary composite outcome was 0.73 (95% confidence interval [CI]: 0.23-1.79), the aHR of primary safety outcome was 0.87 (95% CI: 0.34-1.90), and the aHR of secondary composite outcome was 0.65 (95% CI: 0.32-1.19). All the results were not statistically significant. In secondary analysis, we tested multiple time points of initiating DOACs. Compared with DOAC initiation after >14 days, the primary composite outcomes in the patients in whom DOACs were initiated ≤3, 4-7, and 8-14 days after IS were the same as the findings of the main analysis. After separating patients into different stroke severity groups, the results were similar to those in the main analysis.
No significant association was observed between the timing of using DOACs and ischemic or hemorrhagic outcomes. The findings did not differ among different time points. Although we do not recommend avoiding the initiation of DOACs in the first few days after IS, we should consider that the early initiation of DOACs (≤3 days) would be appropriate only for patients who tend to experience thromboembolic events and have a low risk of bleeding. The optimal timing of initiation still must be confirmed by randomized controlled trials.
房颤（AF）患者会被开具口服抗凝药以预防中风；然而，尚无证据表明在缺血性中风（IS）后的头几天使用直接口服抗凝剂（DOACs）会带来良好预后。本研究评估了IS后使用DOACs的时间与药物有效性和安全性之间的关联，以确定最佳时间。
在这项回顾性队列研究中，我们查阅了台北荣民总医院的电子病历。对开始使用DOACs的患者的1年预后进行评估。比较了不同的起始时间窗（初步分析中起始时间≤3天和>3天）。主要复合结局为中风、短暂性脑缺血发作、全身性栓塞或因IS导致的死亡。主要安全性结局为大出血或具有临床意义的非大出血。次要复合结局为全因死亡率、血栓栓塞事件或急性心肌梗死/出血事件。
本研究纳入了570例患者。AF患者IS后开始使用DOACs的中位起始时间为14天。将DOACs起始时间>3天的患者与起始时间≤3天的患者进行比较，主要复合结局的校正风险比（aHRs）为0.73（95%置信区间[CI]：0.23 - 1.79），主要安全性结局的aHR为0.87（95%CI：0.34 - 1.90），次要复合结局的aHR为0.65（95%CI：0.32 - 1.19）。所有结果均无统计学意义。在二次分析中，我们测试了多个开始使用DOACs的时间点。与IS后>14天开始使用DOACs相比，IS后≤3天、4 - 7天和8 - 14天开始使用DOACs的患者的主要复合结局与主要分析结果相同。将患者分为不同的中风严重程度组后，结果与主要分析相似。
未观察到使用DOACs的时间与缺血性或出血性结局之间存在显著关联。不同时间点的研究结果无差异。虽然我们不建议在IS后的头几天避免开始使用DOACs，但我们应考虑，仅对于有血栓栓塞事件倾向且出血风险低的患者，早期开始使用DOACs（≤3天）才是合适的。起始的最佳时间仍必须通过随机对照试验来确定。
