Optimal Rivaroxaban Dose in Asian Patients With Atrial Fibrillation and Normal or Mildly Impaired Renal Function

Abstract

Background and Purpose - Although rivaroxaban 15 mg (R15) was only given to patients with creatinine clearance (CrCl) ≤50 mL/min in the pivotal clinical trial, this dose has been commonly prescribed in Asian patients with nonvalvular atrial fibrillation regardless of renal function. There is a paucity of information on the clinical outcomes of R15 compared with rivaroxaban 20 mg (R20) in patients with CrCl ≥50 mL/min. This study aimed to examine the effectiveness and safety of 2 doses of rivaroxaban in Asian patients with atrial fibrillation and CrCl ≥50 mL/min. Methods - Using the Korean National Health Insurance Service database, patients with atrial fibrillation and normal or mildly impaired renal function (CrCl ≥50 mL/min) and naive to rivaroxaban or warfarin were included from January 2014 to December 2016. Three separate 1:1 propensity score-matched cohorts were conducted: R20 versus warfarin (n=15 584), R15 versus warfarin (n=11 554), and R20 versus R15 (n=10 392). Hazard ratios for ischemic stroke, intracranial hemorrhage, gastrointestinal bleeding, major bleeding, all-cause death, and composite clinical outcome were analyzed. Results - Compared with warfarin, both R20 and R15 showed significantly lower risk for ischemic stroke, major bleeding (mainly through reduction of intracranial hemorrhage), and all-cause death. Compared with R15, R20 showed better results for the composite clinical outcome (hazard ratio, 0.852; 95% CI, 0.735-0.988). This benefit was consistently observed in patients aged ≥80 years and those <50 kg. R20 was associated with higher risk of major bleeding than R15 in patients with marginal CrCl (50-60 mL/min). Conclusions - Among Asians with atrial fibrillation and CrCl ≥50 mL/min, both R20 and R15 were associated with reduced risk of ischemic stroke, intracranial hemorrhage, major bleeding, and all-cause death without significantly increased risk of gastrointestinal bleeding compared with warfarin. In patients with CrCl ≥50 mL/min, on-label R20 showed better results for the composite clinical outcome compared with off-label R15.