(P-032) Comparative Effectiveness and Safety of Low versus High Dose Rivaroxaban and Apixaban for Atrial Fibrillation: A Propensity Score-matched Cohort Study

Background: Low-dose direct oral anticoagulant (DOAC) use is more prevalent than expected in clinical practice.

Objectives: To assess the efficacy and safety of low- versus high-dose of rivaroxaban and apixaban with similar baseline risk among atrial fibrillation (AF) patients.

Methods: We assembled a cohort of hospitalized patients with a primary or secondary diagnosis of AF and discharged to the community using Quebec administrative databases (Med-Echo and RAMQ) from 2011 to 2018. Cohort entry was defined as the first rivaroxaban (15 or 20 mg daily) and apixaban (2.5 or 5 mg twice daily) claim in new users, defined as no oral anticoagulant (OAC) claims in the prior year. We determined demographics, comorbidities, CHA2DS2-VASc score, HAS-BLED score, Charlson score, and frailty score. We assessed effectiveness (ischemic stroke/systemic embolism (SE), myocardial infarction, death, composite) and safety (intracranial bleeding [ICH], extracranial major bleeding, composite) in the first year following drug initiation between low- and high dose groups. We conducted propensity score (PS) matching to balance the low- and high- dose groups for baseline characteristics, and estimated hazard ratios (HRs) for outcomes using Cox proportional hazard models. All the analyses were conducted to account for competing risks.

Results: After 1:1 PS-matching, we retained 1,285 patients in each rivaroxaban group and respectively, 2,393 patients in each apixaban group. Comparative effectiveness and safety outcomes for low vs high dose rivaroxaban were not significant. For apixaban, we found a greater risk of ischemic stroke/SE/all-cause mortality, all-cause of death and composite of effectiveness (HR: 1.85.82; 95% CI: 1.30-2.65, HR: 2.36; 95% CI: 1.46-3.80, and (HR: 1.62; 95% CI: 1.20-2.18), respectively) for the lower dose compared to high dose group. Yet, we found no association with the bleeding rates.

Conclusions: The study suggest no significant differences in terms of effectiveness or safety outcomes when we compared both dosage of rivaroxaban, however for apixaban the lower dose was associated with a greater risk of death and composite effectiveness outcomes without lowering bleeding rates.