Introduction: Early anticoagulation after cardioembolic stroke remains controversial, due to the potential for symptomatic hemorrhagic transformation (HT). The safety profile of rivaroxaban within 14 days of cardioembolic stroke onset has not been assessed prospectively.
Methods: We conducted a prospective, open label study of patients with atrial fibrillation treated with rivaroxaban ≤14 days of mild/moderate ischemic stroke/TIA (NIHSS score≤8) onset. Informed consent was obtained after the decision to treat with rivaroxaban was made by the treating physician. All patients underwent MRI, including susceptibility-weighted sequences, within 24 hours of rivaroxaban initiation and at day 7, with clinical assessment at 90 days. HT was classified using ECASS criteria (hemorrhagic infarct (HI) 1/2, or parenchymal hemorrhage (PH) 1/2). The primary endpoint was symptomatic HT (defined as PH2 associated with an NIHSS increase ≥4 within the study period). Secondary outcomes included any PH at day 7 and recurrent stroke within 90 days of enrolment.
Results: Sixty patients were enrolled (mean±SD age 71±19 years, 82% stroke/18% TIA). Median (IQR) time from onset to first rivaroxaban dose was 3(5) days. At treatment initiation, median NIHSS was 2(4) and median DWI volume was 7.9(13.7) ml (range 0-175 ml). Baseline DWI volume was correlated with time to first dose (r=0.58, p<0.001). On baseline MRI, HT was present in 25 patients (42%) (HI1=19, HI2=6). Fifty patients had follow-up MRI at a median 7(4) days after rivaroxaban initiation (4 patients withdrew consent and 6 were lost to follow-up). No patients developed symptomatic HT or PH at any point. New asymptomatic HI1 developed in 3 patients. There was asymptomatic progression from HI1 to HI2 in 5 patients. In the remaining 18 patients with baseline HI and follow-up MRI, there was no change at day 7. Two recurrent ischemic strokes occurred (day 5 and day 28). Two additional patients had new asymptomatic DWI lesions at day 7. Two patients died within 90 days (one recurrent stroke and one pneumonia).
Conclusion: These data support the safety of rivaroxaban initiation within 14 days of mild/moderate cardioembolic stroke/TIA. MRI evidence of petechial HT, which is common, does not appear to increase the risk of symptomatic HT.