Supplementary Material for: IV-Thrombolysis for Acute Ischemic Stroke with Unknown Onset in Patients on Oral Anticoagulation

Abstract
Introduction
IV-thrombolysis is established in the unknown or extended time window based on multimodal imaging. Further, increasing evidence exists regarding IV-thrombolysis in patients on oral anticoagulation including direct oral anticoagulants (DOAC). However, data on IV-thrombolysis in ischemic stroke patients on oral anticoagulation with unknown time of stroke onset is sparse.

Methods
This study bases on the longitudinal cohort study Stroke Research Consortium in Northern Bavaria (STAMINA; ClinicalTrials.gov Identifier: NCT04357899). Acute ischemic stroke patients treated with iv-thrombolysis (IVT) in the unknown or extended time window from January 2015 to December 2019 were included. Patient selection based on multimodal CT or MRI. Patients on oral anticoagulation (vitamin-K antagonist (VKA) or DOAC within 48 hours) were eligible for IV-thrombolysis based on INR-measurement (VKA) or plasma levels (DOAC) according to an institutional protocol. Primary outcomes were the incidence of any and symptomatic intracranial hemorrhage.

Results
Of 170 ischemic stroke patients treated with IV-thrombolysis in the unknown or extended time window, 151 had no oral anticoagulation at stroke onset and 19 were on oral anticoagulation (6 on vitamin-K antagonist (VKA) and 13 on direct oral anticoagulant (DOAC)). The risk of symptomatic ICH according to ECASS II criteria was similar between the patients with and without oral anticoagulation (1 (5.3%) vs. 4 (2.7%); p=0.453). After adjustment for confounding factors pre-medication with oral anticoagulation was not associated with symptomatic ICH (aOR 1.02 (0.09 – 11.02); p=0.988).

Conclusion
IV-thrombolysis for ischemic stroke with unknown onset appeared safe in selected patients on oral anticoagulation with both DOAC and VKA.