title: Monitoring of anti-Xa activity and factors related to bleeding events: A study in Japanese patients with nonvalvular atrial fibrillation receiving rivaroxaban.
abstract: 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 15mg once daily for patients with CrCl 15-49 and CrCl ≥50mL/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±0.15IU/mL; p<0.001). The peak AXA level significantly differed among patients with CrCl 15-29, 30-49, 50-79, and ≥80mL/min (2.51±0.83, 1.72±0.76, 2.05±0.82, and 1.66±0.51IU/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±0.80IU/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).
  
  
  CONCLUSIONS
  Peak AXA level was an independent predictor for bleeding events in Japanese NVAF patients receiving rivaroxaban.
authors.affiliation: Department of Cardiology, Nagoya University Graduate School of Medicine, Nagoya, Japan; Department of Cardiovascular Medicine, Tosei General Hospital, Seto, Japan.
authors.forename: Teruhiro
authors.initials: T
authors.lastname: Sakaguchi
authors.affiliation: Department of Cardiovascular Medicine, Tosei General Hospital, Seto, Japan.
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Osanai
authors.affiliation: Department of Cardiovascular Medicine, Tosei General Hospital, Seto, Japan.
authors.forename: Yosuke
authors.initials: Y
authors.lastname: Murase
authors.affiliation: Department of Cardiology, Nagoya University Graduate School of Medicine, Nagoya, Japan. Electronic address: hkishii@med.nagoya-u.ac.jp.
authors.forename: Hideki
authors.initials: H
authors.lastname: Ishii
authors.affiliation: Department of Cardiovascular Medicine, Tosei General Hospital, Seto, Japan.
authors.forename: Yoshihito
authors.initials: Y
authors.lastname: Nakashima
authors.affiliation: Department of Cardiovascular Medicine, Tosei General Hospital, Seto, Japan.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Asano
authors.affiliation: Department of Cardiology, Nagoya University Graduate School of Medicine, Nagoya, Japan.
authors.forename: Susumu
authors.initials: S
authors.lastname: Suzuki
authors.affiliation: Department of Cardiology, Nagoya University Graduate School of Medicine, Nagoya, Japan.
authors.forename: Mikito
authors.initials: M
authors.lastname: Takefuji
authors.affiliation: Department of Cardiology, Nagoya University Graduate School of Medicine, Nagoya, Japan.
authors.forename: Yasuya
authors.initials: Y
authors.lastname: Inden
authors.affiliation: Department of Cardiovascular Medicine, Tosei General Hospital, Seto, Japan.
authors.forename: Kazuyoshi
authors.initials: K
authors.lastname: Sakai
authors.affiliation: Department of Cardiology, Nagoya University Graduate School of Medicine, Nagoya, Japan.
authors.forename: Toyoaki
authors.initials: T
authors.lastname: Murohara
authors.affiliation: Department of Cardiovascular Medicine, Tosei General Hospital, Seto, Japan.
authors.forename: Masayoshi
authors.initials: M
authors.lastname: Ajioka
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D044466:Asian People; D001281:Atrial Fibrillation / Q000188:drug therapy* / Q000378:metabolism; D065427:Factor Xa Inhibitors / Q000009:adverse effects* / Q000097:blood / Q000493:pharmacokinetics; D005260:Female; D006470:Hemorrhage / Q000139:chemically induced* / Q000378:metabolism; D006801:Humans; D008297:Male; D008875:Middle Aged; D000069552:Rivaroxaban / Q000009:adverse effects* / Q000097:blood / Q000493:pharmacokinetics
chemical_list: D065427:Factor Xa Inhibitors; D000069552:Rivaroxaban
keywords: Bleeding complication; Coagulation test; Factor Xa inhibitor; Nonvalvular atrial fibrillation