Abstract WP203: Effects Of Oral Factor Xa Inhibitors On Ischemic Stroke In Patients Without Atrial Fibrillation: Systematic Review Of Randomized Clinical Trials

Background and Purpose: To assess the effects of oral factor Xa inhibitors for prevention of ischemic stroke in patients without a history of atrial fibrillation. Methods: Systematic review of randomized clinical trials (RCTs) testing oral factor Xa inhibitors in patients without a history of atrial fibrillation that reported ischemic stroke. Results: Twenty-two RCTs reported 1194 ischemic strokes: five RCTs testing apixaban (75 ischemic strokes), one RCT each testing betrixaban (52 ischemic strokes) and edoxaban (1 ischemic stroke), and 15 RCTs testing rivaroxaban (1066 ischemic strokes). Three double-blinded RCTs reported statistically significant reductions in ischemic stroke: Two comparing rivaroxaban 2.5mg twice daily versus placebo in patients with cardiovascular disease (COMPASS, hazard ratio (HR) 0.51, 95%CI 0.38-0.68 and COMMANDER-HF, HR 0.64, 95%CI 0.43-0.95), and a third trial compared betrixaban 80mg daily with enoxaparin followed by placebo in patients hospitalized for acute medical illness (APEX, relative risk 0.53, 95%CI 0.30-0.94). Compared with aspirin, rivaroxaban 5mg twice daily significantly reduced ischemic stroke in patients with chronic atherosclerosis in COMPASS (HR 0.69, 95%CI 0.53-0.90), but in contrast rivaroxaban 15mg daily vs. aspirin showed no reduction in ischemic stroke in patients with recent embolic stroke in the large NAVIGATE ESUS trial (HR 1.01, 95%CI 0.81-1.26). Comparisons from 18 other RCTs were inconclusive, although trends consistently showed numerically fewer ischemic strokes among those assigned oral fXa inhibitors compared with placebo. Conclusions: There is convincing evidence that oral factor Xa inhibitors reduce ischemic stroke in patients without a history of atrial fibrillation. The strongest evidence was for rivaroxaban 2.5mg twice daily when given with aspirin in patients with cardiovascular disease. Reduction in ischemic stroke by other dosages, by other factor Xa inhibitors, and when given without antiplatelet agents is less certain. The contribution of atrial fibrillation-related stroke unlikely accounts for the observed reductions.