To evaluate the risk of intracerebral hemorrhage (ICH) and early mortality following intravenous thrombolysis (IVT) in patients with acute ischemic stroke (AIS) who had taken direct oral anticoagulants (DOACs) within 48 hours prior to symptom onset.

The safety of IVT in patients receiving recent DOAC therapy remains uncertain. Current guidelines discourage thrombolysis due to bleeding concerns, although these recommendations are based on limited evidence. Emerging data suggest that selected patients on DOACs might safely undergo reperfusion therapy, but comparative analyses remain limited.

We conducted a retrospective comparative cohort study using the TriNetX Research Network, which aggregates data from 111 healthcare organizations. Adult patients with acute cerebral infarction and documented DOAC use within 48 hours prior to stroke onset were identified. Patients were divided into two cohorts: those who received IVT despite recent DOAC use (DOAC + IVT) and those treated with IVT without recent DOAC exposure (IVT alone). Patients with outcomes preceding the index event were excluded. Propensity score matching (1:1) balanced demographics, vascular risk factors, comorbidities, and medication use. Primary outcomes were intracerebral hemorrhage and all-cause mortality within 2 days.

After matching, 1,529 patients were included in each cohort. Within 2 days, intracerebral hemorrhage occurred in 1.3% of the DOAC + IVT group versus 2.6% of the IVT-alone group (risk ratio [RR] 0.52; 95% CI 0.30–0.87; p < 0.001), representing a 1.3% absolute risk reduction. Early mortality was also lower in patients receiving IVT despite recent DOAC use (RR 0.34; 95% CI 0.22–0.52; p < 0.001).

IVT within 48 hours of DOAC use was not associated with increased ICH or early mortality. These findings suggest selected anticoagulated patients might benefit from reperfusion therapy, supporting further prospective studies to refine eligibility criteria.