title: Oral rivaroxaban for Japanese patients with symptomatic venous thromboembolism - the J-EINSTEIN DVT and PE program.
abstract: BACKGROUND
  The global EINSTEIN DVT and PE studies compared rivaroxaban (15 mg twice daily for 3 weeks followed by 20 mg once daily) with enoxaparin/vitamin K antagonist therapy and demonstrated non-inferiority for efficacy and superiority for major bleeding. Owing to differences in targeted anticoagulant intensities in Japan, Japanese patients were not enrolled into the global studies. Instead, a separate study of deep vein thrombosis (DVT) and/or pulmonary embolism (PE) in Japanese patients was conducted, which compared the Japanese standard of care with a reduced dose of rivaroxaban.
  
  
  METHODS
  We conducted an open-label, randomized trial that compared 3, 6, or 12 months of oral rivaroxaban alone (10 mg twice daily or 15 mg twice daily for 3 weeks followed by 15 mg once daily) with activated partial thromboplastin time-adjusted intravenous unfractionated heparin (UFH) followed by warfarin (target international normalized ratio 2.0; range 1.5-2.5) in patients with acute, objectively confirmed symptomatic DVT and/or PE. Patients were assessed for the occurrence of symptomatic recurrent venous thromboembolic events or asymptomatic deterioration and bleeding.
  
  
  RESULTS
  Eighty-one patients were assigned to rivaroxaban and 19 patients to UFH/warfarin. Three patients were excluded because of serious non-compliance issues. The composite of symptomatic venous thromboembolic events or asymptomatic deterioration occurred in 1 (1.4%) rivaroxaban patient and in 1 (5.3%) UFH/warfarin patient (absolute risk difference, 3.9% [95% confidence interval, -3.4-23.8]). No major bleeding occurred during study treatment. Clinically relevant non-major bleeding occurred in 6 (7.8%) patients in the rivaroxaban group and 1 (5.3%) patient in the UFH/warfarin group.
  
  
  CONCLUSIONS
  The findings of this study in Japanese patients with acute DVT and/or PE suggest a similar efficacy and safety profile with rivaroxaban and control treatment, consistent with that of the worldwide EINSTEIN DVT and PE program.
  
  
  BACKGROUND
  Clinicaltrials.gov: NCT01516840 and NCT01516814.
authors.affiliation: Department of Cardiology and Nephrology, Mie University Graduate School of Medicine, Mie, 514-8507 Japan.
authors.forename: Norikazu
authors.initials: N
authors.lastname: Yamada
authors.affiliation: Division of Cardiology, Department of Medicine, Nihon University School of Medicine, Tokyo, Japan.
authors.forename: Atsushi
authors.initials: A
authors.lastname: Hirayama
authors.affiliation: Division of Cardiovascular, Respiratory and general surgery, Nihon University School of Medicine, Tokyo, Japan.
authors.forename: Hideaki
authors.initials: H
authors.lastname: Maeda
authors.affiliation: Department of Cardiology, National Hospital Organization, Kanazawa Medical Center, Kanazawa, Japan.
authors.forename: Satoru
authors.initials: S
authors.lastname: Sakagami
authors.affiliation: Department of Cardiovascular Surgery, Kanazawa Medical University, Ishikawa, Japan.
authors.forename: Hiroo
authors.initials: H
authors.lastname: Shikata
authors.affiliation: Maastricht University Medical Center, Maastricht, The Netherlands.
authors.forename: Martin H
authors.initials: MH
authors.lastname: Prins
authors.affiliation: Bayer HealthCare Pharmaceuticals, Wuppertal, Germany.
authors.forename: Anthonie Wa
authors.initials: AW
authors.lastname: Lensing
authors.affiliation: Bayer Yakuhin Ltd, Osaka, Japan.
authors.forename: Masaharu
authors.initials: M
authors.lastname: Kato
authors.affiliation: Bayer Yakuhin Ltd, Osaka, Japan.
authors.forename: Junichi
authors.initials: J
authors.lastname: Onuma
authors.affiliation: Bayer Yakuhin Ltd, Osaka, Japan.
authors.forename: Yuki
authors.initials: Y
authors.lastname: Miyamoto
authors.affiliation: Bayer Yakuhin Ltd, Osaka, Japan.
authors.forename: Kazuma
authors.initials: K
authors.lastname: Iekushi
authors.affiliation: Bayer Yakuhin Ltd, Osaka, Japan.
authors.forename: Mariko
authors.initials: M
authors.lastname: Kajikawa
keywords: Deep vein thrombosis; Japan; Pulmonary embolism; Randomized trial; Rivaroxaban; Unfractionated heparin; Venous thromboembolism; Warfarin