Risk of spontaneous intracerebral hemorrhage associated with NOACs compared with aspirin and warfarin: A long-term single hospital follow-up study

Background: Non-vitamin K antagonist oral anticoagulants (NOACs) are currently the mainstay treatment for preventing thrombosis-induced ischemic stroke in patients with atrial fibrillation (AF), deep vein thrombosis (DVT), or previous infarction. However, such management may potentially induce antithrombotic-associated intracranial hemorrhage, leading to significantly adverse clinical outcomes. To investigate the risk of spontaneous intracranial hemorrhage (sICH) in patients under therapeutic anticoagulation. Methods: This retrospective cohort study used a database established by Kaohsiung Veterans General Hospital to estimate the risk of first onset sICH in patients with AF, DVT or previous stroke who were 18 years old or older, and who had been on at least three months continuous long-term treatment with the oral anticoagulants aspirin, warfarin, or NOACs. In addition, we used propensity-score matching to minimize bias and Cox proportional hazards ratio to compare the risk of sICH among patients prescribed these anticoagulants. Results: We analyzed the data of 546 patients (182 aspirin users, 182 warfarin users, and 182 NOAC users). 180 (20 taking aspirin, 74 warfarin, and 86 NOACs) developed new onset sICH before seven years. No new onset cases were found after 7 years. Importantly, those taking NOACs were found to be at a higher risk of early onset hemorrhage (47.80 %) compared to the groups taking aspirin (11.10 %) and warfarin (47.80 %) with a median time-to-occurrence being 2.50, 4.00, and 4.40 years, respectively. Conclusions: Though NOACs prevented ischemic stroke, they were used with a higher risk of early onset spontaneous ICH at our large medical center.