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. (C) 2016 Japanese College of Cardiology. Published by Elsevier Ltd. All rights reserved.