Low-Dose Rivaroxaban and Risks of Adverse Events in Patients with Atrial Fibrillation

Background and Purpose - In the daily practice, low-dose nonvitamin K antagonist oral anticoagulants are commonly used among Asian patients with atrial fibrillation (AF). The aim of the present study was to compare the risks of ischemic stroke, intracranial hemorrhage, and net clinical benefit of Asian patients with AF treated with off-label low-dose and on-label dosing rivaroxaban. Methods - A total of 2214 patients with AF aged ≥20 years treated with rivaroxaban at a tertiary medical center in Taiwan were studied. Patients were categorized into 2 groups: (1) on-label dose (n=1630): ROCKET-AF or J-ROCKET dosage criteria; and (2) off-label low-dose (10 mg/d for patients with an estimated glomerulus filtration rate >50 mL/min, n=584). The risks of ischemic stroke and intracranial hemorrhage were compared between 2 groups. Results - Compared with the on-label dose group, off-label low-dose rivaroxaban was associated with an increased risk of ischemic stroke with an adjusted hazard ratio of 2.75; 95% CI =1.62-4.69; P<0.001). The risk intracranial hemorrhage did not differ significantly between the on-label and off-label low-dosing groups (adjusted hazard ratio =0.62; 95% CI =0.32-1.20; P=0.213). Compared with off-label low-dose group, on-label dosing rivaroxaban was associated with a positive net clinical benefit in different weighted models. The results were consistent among the propensity-matched cohort. Conclusions - Off-label low-dosing rivaroxaban should be avoided for Asian patients with AF giving the higher risk of ischemic stroke without risk reduction in intracranial hemorrhage compared with on-label dosing.