title: Edoxaban versus warfarin for the treatment of symptomatic venous thromboembolism.
abstract: BACKGROUND
  Whether the oral factor Xa inhibitor edoxaban can be an alternative to warfarin in patients with venous thromboembolism is unclear.
  
  
  METHODS
  In a randomized, double-blind, noninferiority study, we randomly assigned patients with acute venous thromboembolism, who had initially received heparin, to receive edoxaban at a dose of 60 mg once daily, or 30 mg once daily (e.g., in the case of patients with creatinine clearance of 30 to 50 ml per minute or a body weight below 60 kg), or to receive warfarin. Patients received the study drug for 3 to 12 months. The primary efficacy outcome was recurrent symptomatic venous thromboembolism. The principal safety outcome was major or clinically relevant nonmajor bleeding.
  
  
  RESULTS
  A total of 4921 patients presented with deep-vein thrombosis, and 3319 with a pulmonary embolism. Among patients receiving warfarin, the time in the therapeutic range was 63.5%. Edoxaban was noninferior to warfarin with respect to the primary efficacy outcome, which occurred in 130 patients in the edoxaban group (3.2%) and 146 patients in the warfarin group (3.5%) (hazard ratio, 0.89; 95% confidence interval [CI], 0.70 to 1.13; P<0.001 for noninferiority). The safety outcome occurred in 349 patients (8.5%) in the edoxaban group and 423 patients (10.3%) in the warfarin group (hazard ratio, 0.81; 95% CI, 0.71 to 0.94; P=0.004 for superiority). The rates of other adverse events were similar in the two groups. A total of 938 patients with pulmonary embolism had right ventricular dysfunction, as assessed by measurement of N-terminal pro-brain natriuretic peptide levels; the rate of recurrent venous thromboembolism in this subgroup was 3.3% in the edoxaban group and 6.2% in the warfarin group (hazard ratio, 0.52; 95% CI, 0.28 to 0.98).
  
  
  CONCLUSIONS
  Edoxaban administered once daily after initial treatment with heparin was noninferior to high-quality standard therapy and caused significantly less bleeding in a broad spectrum of patients with venous thromboembolism, including those with severe pulmonary embolism. (Funded by Daiichi-Sankyo; Hokusai-VTE ClinicalTrials.gov number, NCT00986154.).
authors.forename: Harry R
authors.initials: HR
authors.lastname: Büller
authors.forename: Hervé
authors.initials: H
authors.lastname: Décousus
authors.forename: Michael A
authors.initials: MA
authors.lastname: Grosso
authors.forename: Michele
authors.initials: M
authors.lastname: Mercuri
authors.forename: Saskia
authors.initials: S
authors.lastname: Middeldorp
authors.forename: Martin H
authors.initials: MH
authors.lastname: Prins
authors.forename: Gary E
authors.initials: GE
authors.lastname: Raskob
authors.forename: Sebastian M
authors.initials: SM
authors.lastname: Schellong
authors.forename: Lee
authors.initials: L
authors.lastname: Schwocho
authors.forename: Annelise
authors.initials: A
authors.lastname: Segers
authors.forename: Minggao
authors.initials: M
authors.lastname: Shi
authors.forename: Peter
authors.initials: P
authors.lastname: Verhamme
authors.forename: Phil
authors.initials: P
authors.lastname: Wells
mesh_terms: D000368:Aged; D000925:Anticoagulants / Q000009:adverse effects / Q000627:therapeutic use*; D004311:Double-Blind Method; D004334:Drug Administration Schedule; D017984:Enoxaparin / Q000009:adverse effects / Q000627:therapeutic use*; D005260:Female; D006470:Hemorrhage / Q000139:chemically induced; D006801:Humans; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D011655:Pulmonary Embolism / Q000188:drug therapy; D054556:Venous Thromboembolism / Q000188:drug therapy*; D014859:Warfarin / Q000009:adverse effects / Q000627:therapeutic use*
chemical_list: D000925:Anticoagulants; D017984:Enoxaparin; D014859:Warfarin