美国德克萨斯大学西南医学中心Ying Xian团队研究了阿替普酶治疗的急性缺血性卒中患者近期使用非维生素K拮抗剂口服抗凝剂与颅内出血的关系。相关论文于2022年2月10日发表于《美国医学会杂志》。

目前指南建议急性缺血性脑卒中患者在服用非维生素K拮抗剂口服抗凝剂（NOACs）时不应静脉使用阿替普酶。

为了评估卒中前服用NOACs的患者静脉注射阿替普酶的安全性和功能性结局，并与未服用长期抗凝剂的患者的预后进行比较，2015年4月至2020年3月，研究组在1752家参与Get with the Guidelines-Stroke项目的美国医院中进行了一项回顾性队列研究，共招募了163038例患者。

这些急性缺血性中风患者在中风前服用NOACs或不服用抗凝剂，并在症状出现后4.5小时内静脉注射阿替普酶。服用NOACs的患者在阿替普酶治疗前7天内使用过NOACs进行预激治疗。

主要结局是静脉注射阿替普酶后36小时内出现症状性颅内出血。4项次要安全性结局包括住院患者死亡率，出院时评估的7项次要功能性结局包括出院回家的患者比例。

163038名接受静脉注射阿替普酶治疗的患者中位年龄为70岁，49.1%为女性；2207名（1.4%）接受了NOACs治疗，160831名（98.6%）在中风前未服用抗凝剂。服用NOAC的患者年龄较大，中位年龄为75岁，而未服用抗凝剂的患者中位年龄为为70岁。服用NOAC的患者心血管并发症的患病率较高，并经历了更严重的中风。

服用NOACs的患者未校正的症状性颅内出血率为3.7%，而未服用抗凝剂的患者为3.2%。校正基线临床因素后，两组之间出现症状性颅内出血的风险没有显著差异，校正后的优势比（OR）为0.88。

二级安全性结局没有显著差异，其中服用NOACs的住院患者死亡率为6.3%，未服用抗凝剂的住院患者为4.9%，校正后的OR为0.84。在7项次要功能结局中，有4项在校正后表现出有利于NOAC组的显著差异，包括出院回家的患者比例，分别为45.9%和53.6%。

研究结果表明，在静脉注射阿替普酶治疗的急性缺血性卒中患者中，与未使用抗凝剂相比，在前7天内使用NOACs与颅内出血风险显著增加无关。

附：英文原文

Title: Association of Recent Use of Non–Vitamin K Antagonist Oral Anticoagulants With Intracranial Hemorrhage Among Patients With Acute Ischemic Stroke Treated With Alteplase

Author: Wayneho Kam, DaJuanicia N. Holmes, Adrian F. Hernandez, Jeffrey L. Saver, Gregg C. Fonarow, Eric E. Smith, Deepak L. Bhatt, Lee H. Schwamm, Mathew J. Reeves, Roland A. Matsouaka, Yosef M. Khan, Martin Unverdorben, Mary C. Birmingham, Patrick D. Lyden, Andrew W. Asimos, Dorothea Altschul, Timothy L. Schoonover, Mouhammad A. Jumaa, Jason T. Nomura, Muhammad Fareed K. Suri, S. Arthur Moore, Eugene F. Lafranchise, DaiWai Olson, Eric D. Peterson, Ying Xian

Issue&Volume: 2022-02-10

Abstract:

Importance  Current guidelines recommend against use of intravenous alteplase in patients with acute ischemic stroke who are taking non–vitamin K antagonist oral anticoagulants (NOACs).

Objective  To evaluate the safety and functional outcomes of intravenous alteplase among patients who were taking NOACs prior to stroke and compare outcomes with patients who were not taking long-term anticoagulants.

Design, Setting, and Participants  A retrospective cohort study of 163038 patients with acute ischemic stroke either taking NOACs or not taking anticoagulants prior to stroke and treated with intravenous alteplase within 4.5 hours of symptom onset at 1752 US hospitals participating in the Get With The Guidelines–Stroke program between April 2015 and March 2020, with complementary data from the Addressing Real-world Anticoagulant Management Issues in Stroke registry.

Exposures  Prestroke treatment with NOACs within 7 days prior to alteplase treatment.

Main Outcomes and Measures  The primary outcome was symptomatic intracranial hemorrhage occurring within 36 hours after intravenous alteplase administration. There were 4 secondary safety outcomes, including inpatient mortality, and 7 secondary functional outcomes assessed at hospital discharge, including the proportion of patients discharged home.

Results  Of 163038 patients treated with intravenous alteplase (median age, 70 [IQR, 59 to 81] years; 49.1% women), 2207 (1.4%) were taking NOACs and 160831 (98.6%) were not taking anticoagulants prior to their stroke. Patients taking NOACs were older (median age, 75 [IQR, 64 to 82] years vs 70 [IQR, 58 to 81] years for those not taking anticoagulants), had a higher prevalence of cardiovascular comorbidities, and experienced more severe strokes (median National Institutes of Health Stroke Scale score, 10 [IQR, 5 to 17] vs 7 [IQR, 4 to 14]) (all standardized differences >10). The unadjusted rate of symptomatic intracranial hemorrhage was 3.7% (95% CI, 2.9% to 4.5%) for patients taking NOACs vs 3.2% (95% CI, 3.1% to 3.3%) for patients not taking anticoagulants. After adjusting for baseline clinical factors, the risk of symptomatic intracranial hemorrhage was not significantly different between groups (adjusted odds ratio [OR], 0.88 [95% CI, 0.70 to 1.10]; adjusted risk difference [RD], 0.51% [95% CI, 1.36% to 0.34%]). There were no significant differences in the secondary safety outcomes, including inpatient mortality (6.3% for patients taking NOACs vs 4.9% for patients not taking anticoagulants; adjusted OR, 0.84 [95% CI, 0.69 to 1.01]; adjusted RD, 1.20% [95% CI, 2.39% to 0%]). Of the secondary functional outcomes, 4 of 7 showed significant differences in favor of the NOAC group after adjustment, including the proportion of patients discharged home (45.9% vs 53.6% for patients not taking anticoagulants; adjusted OR, 1.17 [95% CI, 1.06 to 1.29]; adjusted RD, 3.84% [95% CI, 1.46% to 6.22%]).

Conclusions and Relevance  Among patients with acute ischemic stroke treated with intravenous alteplase, use of NOACs within the preceding 7 days, compared with no use of anticoagulants, was not associated with a significantly increased risk of intracranial hemorrhage.

DOI: 10.1001/jama.2022.0948

Source: https://jamanetwork.com/journals/jama/fullarticle/2789099