Abstract 21: Effect of Oral Factor Xa Inhibitors on the Risk of Subdural Hematoma: COMPASS trial Results and Systematic Review

Background: Subdural Hematomas (SDHs) are an uncommon but important complication of anticoagulation therapy. Data on SDHs has been underreported from major randomized trials testing novel oral anticoagulants, and the risk of SDHs relative to aspirin has not been defined. Methods: We assessed the frequency and the effects of antithrombotic treatments on SDHs in the recent international COMPASS randomized trial comparing aspirin 100mg daily, Rivaroxaban 5mg twice daily, and Rivaroxaban 2.5mg twice daily plus aspirin. A systematic literature review of randomized trials comparing factor Xa inhibitors versus aspirin on SDH risk was undertaken. Results: A total of 28 SDHs among 27,395 COMPASS participants were identified. The incidence was 0.04 -0.06 per 100 patient-years during the mean 23-month follow-up. The frequency of SDH according to assigned antithrombotic therapy was 11 for Aspirin, 7 for Rivaroxaban and 10 for combined antithrombotic therapy. The rates of SDHs did not differ per treatment groups. Three RCTs comparing Factor Xa inhibitors versus Aspirin and reporting data on SDHs were identified. They involved 16,177 participants (mean age 65) with a total of 11 SDHs. The incidence of SDHs ranged from 0.06 to 0.1 per 100-patient-years (HR 1.51 in one study). Conclusions: The frequency of SDH was similar in all three treatment arms of the COMPASS trial. Based on available evidence from four randomized trials, therapeutic dosages of factor Xa inhibitors do not appear to increase the risk of SDH compared to aspirin. The COMPASS trial results triple the available evidence from randomized comparisons of oral factor Xa inhibitors with aspirin.