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 (I²=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.

中文翻译：

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服用直接口服抗凝剂的患者静脉溶栓的安全性：系统评价和荟萃分析。

背景和目的——关于使用直接口服抗凝剂 (DOAC) 的急性缺血性卒中患者静脉溶栓 (IVT) 安全性的数据很少。方法——我们对当前文献进行了系统回顾和荟萃分析。记录了所有接受 DOAC 预处理的因急性缺血性卒中而接受 IVT 的成年患者的数据。通过比较这些患者（1）未接受过抗凝治疗的卒中患者和（2）国际标准化比率 <1.7 的华法林患者的症状性脑出血发生率进行荟萃分析。在亚组中进一步进行了荟萃分析如下：（1）在 48 小时内给予 DOAC 对比 IVT 前的未知间隔，(2) 根据美国国家神经疾病研究所 (NINDS) 与欧洲合作急性卒中研究 II (ECASS-II) 标准，考虑有症状的脑出血结果。 结果——在审查了 13 392 份报告并与 12 份已发表的某些作者交流后研究中，共有来自 6 项研究的 52 823 名急性缺血性卒中患者参加了本荟萃分析：DOAC：366 名，华法林：2133 名，以及 503 241 名未接受过抗凝治疗的患者。我们在 48 小时内服用 DOACs 的患者中未发现 IVT 后出现症状性脑出血的额外风险——DOACs-华法林：NINDS（优势比 [OR]，0.55 [95% CI，0.19-1.59]），ECASS-II（OR，0.77 [95% CI，0.28–2.16]）；DOAC-无抗凝：NINDS（OR，1.23 [95% CI，0.46–3.31]），ECASS-II（OR，0.87 [95% CI，0.32–2.41]）。相似地，在最后一次 DOAC 摄入之间没有时间限制，没有检测到额外的风险——DOACs 华法林：NINDS (OR, 0.85 [95% CI, 0.49–1.45]), ECASS-II (OR, 1.11 [95% CI, 0.67–1.85]) ; DOACs-无抗凝：NINDS（OR，1.17 [95% CI，0.43-3.15]），ECASS-II（OR，0.87 [95% CI，0.33-2.41]）。没有证据表明纳入研究之间存在异质性（我² = 0％）。我们还提供了 IVT 前有或没有逆转剂的 123 个个案的详细信息。出血性转化 (OR, 1.48 [95% CI, 0.50–4.38])、症状性出血性转化 (OR, 0.47 [95% CI, 0.09–2.55]) 或早期死亡率 (OR, 0.60 [95% CI, 0.11–3.43]) 在接受或未接受溶栓前依达鲁珠单抗治疗的队列之间。与 IVT。