title: Comparison of idrabiotaparinux with vitamin K antagonists for prevention of thromboembolism in patients with atrial fibrillation: the Borealis-Atrial Fibrillation Study.
abstract: BACKGROUND
  Idrabiotaparinux, a long-acting inhibitor of factor Xa, was shown to be effective in the treatment of patients with venous thromboembolism.
  
  
  OBJECTIVE
  To assess non-inferiority for the efficacy of idrabiotaparinux versus warfarin in patients with atrial fibrillation (AF) at risk of stroke and systemic embolism. Bleeding was also assessed.
  
  
  METHODS
  This randomized, double-blind trial enrolled patients with electrocardiogram-documented AF. Idrabiotaparinux was administered weekly via subcutaneous injection, and warfarin was administered daily with dose adjustment to maintain the international normalized ratio between 2.0 and 3.0. Each idrabiotaparinux injection was 3 mg for the first 7 weeks, followed by 2 mg thereafter, except in patients with a creatinine clearance of 30-50 mL min(-1) or aged ≥ 75 years. The patients received 1.5 mg after the first 7 weeks. The efficacy outcome was the composite of all fatal or non-fatal strokes and systemic embolism. The safety outcome was clinically relevant bleeding (major and clinically relevant non-major bleeding).
  
  
  RESULTS
  The study was terminated prematurely by the sponsor for strategic/commercial, not scientific, reasons, with 39% of the planned number of patients included and an average duration of treatment of 240 days. Of the 1886 idrabiotaparinux recipients, 20 developed stroke or systemic embolism (1.5% per year), whereas this occurred in 22 of the 1887 warfarin patients (1.6% per year, hazard ratio 0.98, 95% confidence interval 0.49-1.66). The annual incidence of bleeding was 6.1% in the idrabiotaparinux and 10.0% in the warfarin group (hazard ratio 0.61, 95% confidence interval 0.46-0.81).
  
  
  CONCLUSIONS
  If anything, despite its early termination, the idrabiotaparinux regimen studied suggested a comparable efficacy to dose-adjusted warfarin, with a lower bleeding risk.
authors.affiliation: Department of Vascular Medicine, Academic Medical Center, Amsterdam, the Netherlands.
authors.forename: H R
authors.initials: HR
authors.lastname: Buller
authors.forename: J
authors.initials: J
authors.lastname: Halperin
authors.forename: G J
authors.initials: GJ
authors.lastname: Hankey
authors.forename: G
authors.initials: G
authors.lastname: Pillion
authors.forename: M H
authors.initials: MH
authors.lastname: Prins
authors.forename: G E
authors.initials: GE
authors.lastname: Raskob
mesh_terms: D000284:Administration, Oral; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000925:Anticoagulants / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D001281:Atrial Fibrillation / Q000150:complications / Q000175:diagnosis / Q000188:drug therapy* / Q000401:mortality; D001710:Biotin / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use; D004311:Double-Blind Method; D004334:Drug Administration Schedule; D057239:Early Termination of Clinical Trials; D004562:Electrocardiography; D065427:Factor Xa Inhibitors / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D005260:Female; D006470:Hemorrhage / Q000139:chemically induced; D006801:Humans; D007279:Injections, Subcutaneous; D008297:Male; D008875:Middle Aged; D009844:Oligosaccharides / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D011237:Predictive Value of Tests; D012307:Risk Factors; D020521:Stroke / Q000175:diagnosis / Q000209:etiology / Q000401:mortality / Q000517:prevention & control*; D013923:Thromboembolism / Q000175:diagnosis / Q000209:etiology / Q000401:mortality / Q000517:prevention & control*; D013997:Time Factors; D016896:Treatment Outcome; D014812:Vitamin K / Q000037:antagonists & inhibitors*; D014859:Warfarin / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*
chemical_list: D000925:Anticoagulants; D065427:Factor Xa Inhibitors; D009844:Oligosaccharides; D014812:Vitamin K; D014859:Warfarin; D001710:Biotin; C545956:idrabiotaparinux
keywords: anticoagulants; clinical trial; idrabiotaparinux; pulmonary embolism; venous thrombosis