Hospitalizations for bleeding associated with apixaban versus rivaroxaban according to dose in Medicare beneficiaries

Apixaban and rivaroxaban are the most prescribed direct oral anticoagulants, and the safety of different doses in patients at high risk for bleeding is not fully defined. The objective of this study was to compare the rate of hospitalizations due to bleeding in patients prescribed apixaban versus rivaroxaban at specific doses. We conducted a retrospective cohort study of more than 1.9 million Medicare beneficiaries who filled prescriptions for apixaban or rivaroxaban from 2014 to 2020 using the Medicare Parts A, B, C and D encounter and prescription claims database. The primary outcomes measured were hospitalizations due to bleeding categorized by location (intracranial, gastrointestinal [GI], and other) and all-cause mortality. Among the population studied, 1,022,170 (53 %) filled a prescription for apixaban 5 mg during the study period, followed by rivaroxaban 20 mg (27 %) and rivaroxaban 10 mg (11 %). Compared to the reference group of apixaban 5 mg, combination prescriptions for rivaroxaban 15–20 mg were associated with more than twice the risk of hospitalization due to GI bleeding (hazard ratio [HR] = 2.41, 95 % confidence interval [CI]: 2.15–2.70) and other bleeding (HR = 2.42, 95 % CI: 1.92–3.05) and were associated with a 51 % higher risk of hospitalization due to intracranial bleeding (HR = 1.51, 95 % CI: 1.15–1.98). There were 88,740 (4.6 %) deaths during the study period, with a 27 % increased risk of death associated with prescriptions for apixaban 2.5 mg (HR = 1.27, 95 % CI: 1.24–1.30) and a 19 % decreased risk of death associated with prescriptions for rivaroxaban 10 mg (HR = 0.81, 95 % CI: 0.78–0.85). Rivaroxaban doses of 15 mg and greater were associated with higher bleeding risk. This data may aid clinicians in making an informed decision when prescribing specific doses of apixaban and rivaroxaban, particularly for patients with a high risk of bleeding. • Assessed bleeding risk according to DOAC and dose in Medicare beneficiaries. • Apixaban 5 mg was most common prescription and used as reference group. • Rivaroxaban doses 15 mg and greater associated with higher risk of bleeding events. • Apixaban 2.5 mg and rivaroxaban 10 mg not associated with increased bleeding. • Apixaban 2.5 mg prescriptions associated with increased risk of death.