Monitoring of anti-Xa activity and factors related to bleeding events: A study in Japanese patients with nonvalvular atrial fibrillation receiving rivaroxaban

Background Anti-Xa activity (AXA) in patients with nonvalvular atrial fibrillation (NVAF) and relationship to bleeding events remains unclear. Methods We evaluated AXA in 94 patients at both trough and peak rivaroxaban concentrations. Rivaroxaban dosage was determined according to creatinine clearance (CrCl): 10 and 15 mg once daily for patients with CrCl 15–49 and CrCl ≥50 mL/min, respectively. AXA value distribution and its association with bleeding events were examined in enrolled subjects. Results The mean peak AXA level was significantly higher than the mean trough level (1.98 ± 0.81 vs. 0.16 ± 0.15 IU/mL; p < 0.001). The peak AXA level significantly differed among patients with CrCl 15–29, 30–49, 50–79, and ≥80 mL/min (2.51 ± 0.83, 1.72 ± 0.76, 2.05 ± 0.82, and 1.66 ± 0.51 IU/mL, respectively; p = 0.004). Major and non-major clinically relevant bleeding events occurred in 22 patients (23.4% and 14.6% per year, respectively). The mean peak AXA level was significantly higher in patients who experienced bleeding events than in those who did not (2.40 ± 0.70 vs. 1.84 ± 0.80 IU/mL; p = 0.001). A Cox multivariate analysis showed that the peak AXA level was independently related to the incidence of major and non-major clinically relevant bleeding events (p = 0.012). Cumulative bleeding rates were significantly higher in patients with high peak AXA levels (p < 0.001). Conclusion Peak AXA level was an independent predictor for bleeding events in Japanese NVAF patients receiving rivaroxaban.