Safety of Intravenous Thrombolysis Among Patients Taking Direct Oral Anticoagulants: A Systematic Review and Meta-Analysis

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 50 324 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], 0.53 [95% CI, 0.18-1.52]), 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, 0.92 [95% CI, 0.33-2.55]). 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.