University of Texas Medical Branch, Department of Emergency Medicine, Galveston, Texas.
University of Texas Medical Branch, Department of Pharmacology and Toxicology, Galveston, Texas.
West J Emerg Med. 2024 May;25(3):399-406. doi: 10.5811/westjem.18063.
Alteplase (tPA) is the initial treatment for acute ischemic stroke. Current tPA guidelines exclude patients who took direct oral anticoagulants (DOAC) within the prior 48 hours. In this propensity-matched retrospective study we compared acute ischemic stroke patients treated with tPA who had received DOACs within 48 hours of thrombolysis to those not previously treated with DOACs, regarding three outcomes: mortality; intracranial hemorrhage (ICH); and need for acute blood transfusions (as a marker of significant blood loss).
Using the United States cohort of 54 healthcare organizations in the TriNetx database, we identified 8,582 stroke patients treated with tPA on DOACs within 48 hours of thrombolysis and 46,703 stroke patients treated with tPA not on DOACs since January 1, 2012. We performed propensity score matching on demographic information and seven prior clinical diagnostic groups, resulting in a total of 17,164 acute stroke patients evenly matched between groups. We recorded mortality rates, frequency of ICH, and need for blood transfusions for each group over the ensuing 7- and 30-day periods.
Patients treated with tPA on DOACs had reduced mortality (3.3% vs 7.3%; risk ratio [RR] 0.456; < 0.001), fewer ICHs (6.8% vs 10.1%; RR 0.678; < 0.001), and less risk of major bleeding as measured by frequency of blood transfusions (0.5% vs 1.5%; RR 0.317; < 0.001) at 7 days post thrombolytic, than the tPA patients not on DOACS. Findings for 30 days post-thrombolytics were similar/statistically significant with lower mortality rate (7.2% vs 13.1%; RR 0.550; < 0.001), fewer ICHs (7.6% vs 10.8%; RR 0.705; < 0.001), and fewer blood transfusions (0.9% vs 2.0%; RR 0.448; < 0.001).
Acute ischemic stroke patients treated with tPA who received DOACs within 48 hours of thrombolysis had lower mortality rates, reduced incidence of ICH, and less blood loss than those not on DOACs. Our study suggests that prior use of DOACs should not be a contraindication to thrombolysis for ischemic stroke.
阿替普酶（tPA）是急性缺血性脑卒中的初始治疗方法。目前的 tPA 指南将在溶栓前 48 小时内服用直接口服抗凝剂（DOAC）的患者排除在外。在这项倾向评分匹配的回顾性研究中，我们比较了在溶栓后 48 小时内接受 DOAC 治疗的接受 tPA 治疗的急性缺血性脑卒中患者与之前未接受 DOAC 治疗的患者，比较了三种结局：死亡率；颅内出血（ICH）；和需要急性输血（作为显著失血的标志物）。
使用 TriNetx 数据库中的美国 54 个医疗保健机构队列，我们确定了 8582 名在溶栓后 48 小时内接受 DOAC 和 tPA 治疗的脑卒中患者，以及自 2012 年 1 月 1 日以来接受 tPA 治疗但未接受 DOAC 治疗的 46703 名脑卒中患者。我们根据人口统计学信息和七个先前的临床诊断组进行了倾向评分匹配，最终共有 17164 名急性脑卒中患者在两组之间进行了均衡匹配。我们记录了每组在接下来的 7 天和 30 天期间的死亡率、ICH 发生率和输血需求。
在溶栓后 7 天内，接受 DOAC 和 tPA 治疗的患者死亡率降低（3.3%比 7.3%；风险比[RR]0.456；<0.001），ICH 发生率降低（6.8%比 10.1%；RR0.678；<0.001），以及输血频率（0.5%比 1.5%）作为衡量大出血风险的指标降低（RR0.317；<0.001），与未接受 DOAC 和 tPA 治疗的患者相比。溶栓后 30 天的结果相似/具有统计学意义，死亡率降低（7.2%比 13.1%；RR0.550；<0.001），ICH 发生率降低（7.6%比 10.8%；RR0.705；<0.001），输血减少（0.9%比 2.0%；RR0.448；<0.001）。
在溶栓后 48 小时内接受 DOAC 和 tPA 治疗的急性缺血性脑卒中患者死亡率较低，ICH 发生率较低，出血较少，与未接受 DOAC 治疗的患者相比。我们的研究表明，在急性缺血性脑卒中患者中，溶栓前使用 DOAC 不应作为溶栓的禁忌症。
