Building Evidence on Safety of Thrombolysis for Patients Undergoing Direct Oral Anticoagulant Treatment

Abstract

Nearly 20% of patients with acute ischemic stroke (AIS) are undergoing direct oral anticoagulant (DOAC) treatment at the time of their stroke. 1 Common indications for DOACs among these patients include stroke prevention from atrial fibrillation, treatment of venous and pulmonary thrombosis, and coronary and peripheral atherosclerotic disease. Novel indications for DOAC use are expected to emerge and may increase the proportion of patients with AIS who are undergoing treatment with DOACs. Current US and European acute stroke treatment guidelines recommend withholding intravenous thrombolysis (thrombolysis), a morbidity-and mortality-saving AIS treatment for patients with recent a DOAC use. 2,3 DOACs have emerged as preferred anticoagulants over vitamin K antagonists due to a favorable safety profile, particularly a lower risk of severe systemic and intracranial hemorrhage (ICH). 4 However, if this translates into a lower risk of hemorrhagic complications of thrombolysis for AIS in the setting of DOAC treatment is yet to be definitively determined as data supporting this practice are limited and heterogenous. The present study by Meinel et al 5 meaningfully advances the field by generating these critical data. Comparative analyses of different patient selection paradigms for thrombolysis in the presence of DOACs provide additional, timely relevance to the study.In this international, multicenter, observational, retrospective analysis of individual patient data from 64 centers, the authors included 832 patients with AIS undergoing intravenous thrombolysis who had ingested a DOAC agent within 48 hours of hospital arrival. Additionally, 32 375 control patients who had received intravenous thrombolysis without prior anticoagulation treatment (defined as having a therapeutic international normalized ratio with vitamin K antagonists or known DOAC treatment) were included for comparison. A priori calculation of the sample size required to detect differences in the primary outcome was not performed. Compared to the control population, patients with recent DOAC ingestion were older and had more comorbidities. They were more likely to have a large vessel occlusion but also had a higher rate of endovascular treatment (62% vs 55%). Dabigatran was the most frequently used DOAC (n = 342, 41%), followed by rivaroxaban (n = 258, 31%) and apixaban (n = 163, 20%). In terms of patient selection strategies used for thrombolysis, DOAC reversal was performed using idarucizumab among 252 patients (30%) receiving dabigatran (no other reversal agents were used among patients receiving other DOACs), 225 patients (27%) had DOAC plasma levels measured, and the remaining 355 patients (43%) had neither plasma drug levels or DOAC re-