title: Betrixaban compared with warfarin in patients with atrial fibrillation: results of a phase 2, randomized, dose-ranging study (Explore-Xa).
abstract: OBJECTIVE
  Patients with atrial fibrillation (AF) are at increased risk of stroke. Betrixaban is a novel oral factor Xa inhibitor administered once daily, mostly excreted unchanged in the bile and with low (17%) renal excretion.
  
  
  RESULTS
  Patients with AF and more than one risk factor for stroke were randomized to one of three blinded doses of betrixaban (40, 60, or 80 mg once daily) or unblinded warfarin, adjusted to an international normalized ratio of 2.0-3.0. The primary outcome was major or clinically relevant non-major bleeding. The mean follow-up was 147 days. Among 508 patients randomized, the mean CHADS2 score was 2.2; 87% of patients had previously received vitamin K antagonist therapy. The time in therapeutic range on warfarin was 63.4%. There were one, five, five, and seven patients with a primary outcome on betrixaban 40, 60, 80 mg daily, or warfarin, respectively. The rate of the primary outcome was lowest on betrixaban 40 mg (hazard ratio compared with warfarin = 0.14, exact stratified log-rank P-value 0.04, unadjusted for multiple testing). Rates of the primary outcome with betrixaban 60 or 80 mg were more similar to those of wafarin. Two ischaemic strokes occurred, one each on betrixaban 60 and 80 mg daily. There were two vascular deaths, one each on betrixaban 40 mg and warfarin. Betrixaban was associated with higher rates of diarrhoea than warfarin.
  
  
  CONCLUSIONS
  Betrixaban was well tolerated and had similar or lower rates of bleeding compared with well-controlled warfarin in patients with AF at risk for stroke.
authors.affiliation: Population Health Research Institute, 237 Barton Street East, Hamilton, Ontario, Canada. connostu@phri.ca
authors.forename: Stuart J
authors.initials: SJ
authors.lastname: Connolly
authors.forename: John
authors.initials: J
authors.lastname: Eikelboom
authors.forename: Paul
authors.initials: P
authors.lastname: Dorian
authors.forename: Stefan H
authors.initials: SH
authors.lastname: Hohnloser
authors.forename: Daniel D
authors.initials: DD
authors.lastname: Gretler
authors.forename: Uma
authors.initials: U
authors.lastname: Sinha
authors.forename: Michael D
authors.initials: MD
authors.lastname: Ezekowitz
mesh_terms: D000368:Aged; D000925:Anticoagulants / Q000008:administration & dosage* / Q000493:pharmacokinetics; D001281:Atrial Fibrillation / Q000150:complications*; D001549:Benzamides / Q000008:administration & dosage* / Q000493:pharmacokinetics; D004305:Dose-Response Relationship, Drug; D005260:Female; D005338:Fibrin Fibrinogen Degradation Products / Q000378:metabolism; D006470:Hemorrhage / Q000139:chemically induced; D006801:Humans; D008297:Male; D011725:Pyridines / Q000008:administration & dosage* / Q000493:pharmacokinetics; D020521:Stroke / Q000517:prevention & control*; D016896:Treatment Outcome; D014859:Warfarin / Q000008:administration & dosage* / Q000493:pharmacokinetics
chemical_list: D000925:Anticoagulants; D001549:Benzamides; D005338:Fibrin Fibrinogen Degradation Products; D011725:Pyridines; C036309:fibrin fragment D; D014859:Warfarin; C543086:betrixaban
keywords: Atrial fibrillation; Betrixaban; Stroke