Impact of three major risk factors on clinical outcomes in patients with nonvalvular atrial fibrillation receiving rivaroxaban: Sub‐analysis from the XAPASS study

BACKGROUND: To evaluate the impact of three risk factors (age [≥75 years], renal impairment [creatinine clearance <50 ml/min], and low body weight [≤50 kg]) on the risk of any bleeding events, all‐cause mortality, and stroke, non‐central nervous system (non‐CNS) systemic embolism (SE), and myocardial infarction (MI) in patients with nonvalvular atrial fibrillation (NVAF) treated with rivaroxaban in a real‐world clinical setting. METHODS: The Xarelto Post‐Authorization Safety and Effectiveness Study in Japanese Patients with Atrial Fibrillation (XAPASS) is a prospective, single‐arm, observational study. Enrolled patients were divided into four subgroups by the number of risk factors. RESULTS: Overall, 9823 patients were included: 4299 with low risk, 2816 with moderate risk, 1574 with high risk, and 1134 with very high risk. The hazard ratios (95% confidence interval) (reference: low risk) for the moderate‐, high‐, and very‐high‐risk groups were 1.62 (1.19, 2.21) (p = 0.002), 2.15 (1.47, 3.15) (p < 0.001), and 2.49 (1.60, 3.87) (p <0.001) for major bleeding, and 1.98 (1.47, 2.66), 2.29 (1.59, 3.29), and 2.74 (1.81, 4.16) (p <0.001 for all) for stroke/non‐CNS SE/MI, respectively. CONCLUSIONS: Age ≥75 years and renal impairment, but not low body weight, were determinants for major bleeding. The accrual of three risk factors was associated with increased risk for major bleeding and stroke/non‐CNS SE/MI in patients with NVAF receiving rivaroxaban; there was no increase in the cumulative risk for these with an increasing number of risk factors.