Acute ischemic stroke on anti-Xa inhibitors: Pharmacokinetics and outcomes

Background and Purpose: Direct oral anticoagulant (DOAC) ingestion within 48 h is an exclusion for thrombolysis in acute ischemic stroke (AIS) patients. We aim to shed light on pharmacokinetic correlates and outcomes in patients with AIS excluded from thrombolysis due to DOAC use. Methods: This is a single center retrospective study of consecutive patients with AIS within 4.5 h from last known normal and excluded from thrombolytic therapy due to confirmed Xa inhibitor DOAC (DOAC_Xa) intake within the prior 48 h. We used linear regression to test the correlation between time from last DOAC_Xa ingestion and anti-Xa level. Results: Over a period of 2.5 years, we identified 44 patients who did not receive thrombolysis because of presumed DOAC intake within 48 h. In adjusted linear regression, there was an association between time from last DOAC ingestion and Xa level (beta = −0.69, p < 0.001). Among the 37 patients with known atrial fibrillation not receiving alteplase due to DOAC use, the 90-day mortality was 35.1% (13/37) and 77% (10/13) of deaths were stroke related. Conclusions: Patients with AIS on DOAC therapy face a heightened risk of mortality. Studies are needed to investigate the safety and efficacy of thrombolysis in such patients based on time of last DOAC ingestion and/or anti-Xa/drug level.