From the Geisinger Neuroscience Institute, Geisinger Health System, Danville, Pennsylvania (S.S., A.S., R.Z.).
Department of Surgical Neurology, Tehran University of Medical Sciences, Iran (S.S.).
Stroke. 2020 Feb;51(2):533-541. doi: 10.1161/STROKEAHA.119.026426. Epub 2019 Dec 30.
Background and Purpose- There are scarce data regarding the safety of intravenous thrombolysis (IVT) in acute ischemic stroke among patients on direct oral anticoagulants (DOACs). Methods- We performed a systematic review and meta-analysis of the current literature. Data regarding all adult patients pretreated with DOAC who received IVT for acute ischemic stroke were recorded. Meta-analysis was performed by comparing the rate of symptomatic intracerebral hemorrhage in these patients with (1) stroke patients without prior anticoagulation therapy and (2) patients on warfarin with international normalized ratio <1.7. Meta-analyses were further conducted in subgroups as follows: (1) administration of DOAC within 48 hours versus an unknown interval before IVT, (2) consideration of symptomatic intracerebral hemorrhage outcome according to the National Institute of Neurological Disorders (NINDS) versus the European Cooperative Acute Stroke Study II (ECASS-II) criteria. Results- After reviewing 13 392 reports and communicating with certain authors of 12 published studies, a total of 52 823 acute ischemic stroke patients from 6 studies were enrolled in the present meta-analysis: DOACs: 366, warfarin: 2133, and 503 241 patients without prior anticoagulation. We detected no additional risk of symptomatic intracerebral hemorrhage following IVT among patients taking DOACs within 48 hours-DOACs-warfarin: NINDS (odds ratio [OR], 0.55 [95% CI, 0.19-1.59]), ECASS-II (OR, 0.77 [95% CI, 0.28-2.16]); DOACs-no-anticoagulation: NINDS (OR, 1.23 [95% CI, 0.46-3.31]), ECASS-II (OR, 0.87 [95% CI, 0.32-2.41]). Similarly, no additional risk was detected with no time limit between last DOAC intake-DOACs warfarin: NINDS (OR, 0.85 [95% CI, 0.49-1.45]), ECASS-II (OR, 1.11 [95% CI, 0.67-1.85]); DOACs-no-anticoagulation: NINDS (OR, 1.17 [95% CI, 0.43-3.15]), ECASS-II (OR, 0.87 [95% CI, 0.33-2.41]). There was no evidence of heterogeneity across included studies (=0%). We also provided the details of 123 individual cases with or without reversal agents before IVT. There was no significant increase in the risk of hemorrhagic transformation (OR, 1.48 [95% CI, 0.50-4.38]), symptomatic hemorrhagic transformation (OR, 0.47 [95% CI, 0.09-2.55]), or early mortality (OR, 0.60 [95% CI, 0.11-3.43]) between cohorts who did or did not receive prethrombolysis idarucizumab. Conclusions- The results of our study indicated that prior intake of DOAC appears not to increase the risk of symptomatic intracerebral hemorrhage in selected AIS patients treated with IVT.
背景与目的-目前关于直接口服抗凝剂（DOAC）治疗的急性缺血性卒中患者接受静脉溶栓（IVT）的安全性数据有限。方法-我们对当前文献进行了系统评价和荟萃分析。记录了所有预先使用 DOAC 治疗且接受急性缺血性卒中 IVT 的成年患者的数据。通过比较这些患者与（1）未接受抗凝治疗的卒中患者和（2）国际标准化比值<1.7 的华法林患者的症状性颅内出血率，进行荟萃分析。亚组分析进一步分为：（1）DOAC 在 IVT 前 48 小时内给药与未知时间间隔给药，（2）根据国立神经病学与卒中研究所（NINDS）与欧洲急性卒中协作研究 II（ECASS-II）标准考虑症状性颅内出血结局。结果-在回顾了 13392 份报告并与 12 项已发表研究的某些作者进行沟通后，共有来自 6 项研究的 52823 例急性缺血性卒中患者纳入本荟萃分析：DOACs：366 例，华法林：2133 例，503241 例未接受抗凝治疗。我们发现，在 DOAC 患者中，在 48 小时内接受 IVT 并没有增加症状性颅内出血的风险-DOACs-华法林：NINDS（比值比[OR]，0.55 [95%置信区间，0.19-1.59]），ECASS-II（OR，0.77 [95%置信区间，0.28-2.16]）；DOACs-无抗凝：NINDS（OR，1.23 [95%置信区间，0.46-3.31]），ECASS-II（OR，0.87 [95%置信区间，0.32-2.41]）。同样，在没有 DOAC 最后一次给药时间限制的情况下，也没有发现额外的风险-DOACs-华法林：NINDS（OR，0.85 [95%置信区间，0.49-1.45]），ECASS-II（OR，1.11 [95%置信区间，0.67-1.85]）；DOACs-无抗凝：NINDS（OR，1.17 [95%置信区间，0.43-3.15]），ECASS-II（OR，0.87 [95%置信区间，0.33-2.41]）。纳入的研究之间没有异质性（=0%）。我们还提供了 123 例接受或未接受 IVT 前逆转剂的个体病例的详细信息。在接受或未接受伊达鲁单抗溶栓前治疗的患者中，出血转化（OR，1.48 [95%置信区间，0.50-4.38]）、症状性出血转化（OR，0.47 [95%置信区间，0.09-2.55]）或早期死亡率（OR，0.60 [95%置信区间，0.11-3.43]）均无显著增加。结论-我们的研究结果表明，在接受 IVT 的特定 AIS 患者中，预先使用 DOAC 似乎不会增加症状性颅内出血的风险。
