title: Anticoagulation intensity of rivaroxaban for stroke patients at a special low dosage in Japan.
abstract: OBJECTIVE
  In Japan, low-dose rivaroxaban [15 mg QD/10 mg QD for creatinine clearance of 30-49 mL/min] was approved for clinical use in NVAF patients partly because of its unique pharmacokinetics in Japanese subjects. The aim of the study was to determine the anticoagulation intensity of rivaroxaban and its determinant factors in Japanese stroke patients.
  
  
  METHODS
  Consecutive stroke patients with NVAF admitted between July 2012 and December 2013 were studied. Prothrombin time (PT), activated partial thromboplastin time (aPTT), and estimated plasma concentration of rivaroxaban (Criv) based on an anti-factor Xa chromogenic assay were measured just before and 4 and 9 h after administration at the steady state level of rivaroxaban. Determinant factors for Criv were explored using a linear mixed-model approach.
  
  
  RESULTS
  Of 110 patients (37 women, 75±9 years old), 59 took 15 mg QD of rivaroxaban and 51 took 10 mg QD. Criv at 4 h was 186 ng/mL for patients taking 15 mg QD and 147 ng/mL for those taking 10 mg QD. Both PT and aPTT were positively correlated with Criv. Criv was 72% lower at 4 h in 15 patients receiving crushed tablets than in the other patients, and tablet crushing was significantly associated with lower Criv (adjusted estimate -0.43, 95% CI -0.60 to -0.26) after multivariate-adjustment.
  
  
  CONCLUSIONS
  The anticoagulation effects of rivaroxaban in the acute stroke setting for Japanese NVAF patients were relatively low as compared with those in the ROCKET-AF and J-ROCKET AF trials. Tablet crushing, common in dysphagic patients, decreased Criv.
authors.affiliation: Department of Cerebrovascular Medicine, National Cerebral and Cardiovascular Center, Osaka, Japan.
authors.forename: Takuya
authors.initials: T
authors.lastname: Okata
authors.affiliation: Department of Cerebrovascular Medicine, National Cerebral and Cardiovascular Center, Osaka, Japan.
authors.forename: Kazunori
authors.initials: K
authors.lastname: Toyoda
authors.affiliation: Department of Clinical Chemistory, National Cerebral and Cardiovascular Center, Osaka, Japan.
authors.forename: Akira
authors.initials: A
authors.lastname: Okamoto
authors.affiliation: Department of Molecular Pathogenesis, National Cerebral and Cardiovascular Center, Osaka, Japan.
authors.forename: Toshiyuki
authors.initials: T
authors.lastname: Miyata
authors.affiliation: Department of Neurology, National Cerebral and Cardiovascular Center, Osaka, Japan.
authors.forename: Kazuyuki
authors.initials: K
authors.lastname: Nagatsuka
authors.affiliation: Department of Cerebrovascular Medicine, National Cerebral and Cardiovascular Center, Osaka, Japan.
authors.forename: Kazuo
authors.initials: K
authors.lastname: Minematsu
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000925:Anticoagulants / Q000627:therapeutic use*; D044466:Asian People; D001281:Atrial Fibrillation / Q000150:complications* / Q000208:ethnology; D001777:Blood Coagulation / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; D007564:Japan; D008297:Male; D008875:Middle Aged; D017063:Outcome Assessment, Health Care; D010314:Partial Thromboplastin Time; D011517:Prothrombin Time; D000069552:Rivaroxaban / Q000627:therapeutic use*; D020521:Stroke / Q000208:ethnology / Q000209:etiology / Q000517:prevention & control*; D013923:Thromboembolism / Q000208:ethnology / Q000209:etiology / Q000517:prevention & control
chemical_list: D000925:Anticoagulants; D000069552:Rivaroxaban