title: Anticoagulation with otamixaban and ischemic events in non-ST-segment elevation acute coronary syndromes: the TAO randomized clinical trial.
abstract: OBJECTIVE
  The optimal anticoagulant for patients with non-ST-segment elevation acute coronary syndromes (NSTE-ACS) managed with an invasive strategy remains controversial.
  
  
  OBJECTIVE
  To compare the clinical efficacy and safety of otamixaban, a novel intravenous direct factor Xa inhibitor, with that of unfractionated heparin plus downstream eptifibatide in patients with NSTE-ACS undergoing a planned early invasive strategy.
  
  
  METHODS
  Randomized, double-blind, active-controlled superiority trial that enrolled 13,229 patients with NSTE-ACS and a planned early invasive strategy, at 568 active sites in 55 countries and conducted between April 2010 and February 2013. A planned interim analysis was conducted for otamixaban dose selection.
  
  
  METHODS
  Eligible participants were randomized to otamixaban (bolus and infusion, at 1 of 2 doses) or unfractionated heparin plus, at the time of percutaneous coronary intervention, eptifibatide. The otamixaban dose selected at interim analysis was an intravenous bolus of 0.080 mg/kg followed by an infusion of 0.140 mg/kg per hour.
  
  
  METHODS
  The primary efficacy outcome was the composite of all-cause death or new myocardial infarction through day 7.
  
  
  RESULTS
  Rates of the primary efficacy outcome were 5.5% (279 of 5105 patients) randomized to receive otamixaban and 5.7% (310 of 5466 patients) randomized to receive unfractionated heparin plus eptifibatide (adjusted relative risk, 0.99 [95% CI, 0.85-1.16]; P = .93). There were no differences for the secondary end points, including procedural thrombotic complications. The primary safety outcome of Thrombosis in Myocardial Infarction major or minor bleeding through day 7 was increased by otamixaban (3.1% vs 1.5%; relative risk, 2.13 [95% CI, 1.63-2.78]; P < .001). Results were consistent across prespecified subgroups.
  
  
  CONCLUSIONS
  Otamixaban did not reduce the rate of ischemic events relative to unfractionated heparin plus eptifibatide but did increase bleeding. These findings do not support the use of otamixaban for patients with NSTE-ACS undergoing planned early percutaneous coronary intervention.
  
  
  BACKGROUND
  clinicaltrials.gov Identifier: NCT01076764.
authors.affiliation: Université Paris-Diderot, Sorbonne-Paris Cité, Paris, France. gabriel.steg@bch.aphp.fr
authors.forename: Philippe Gabriel
authors.initials: PG
authors.lastname: Steg
authors.forename: Shamir R
authors.initials: SR
authors.lastname: Mehta
authors.forename: Charles V
authors.initials: CV
authors.lastname: Pollack
authors.forename: Christoph
authors.initials: C
authors.lastname: Bode
authors.forename: Marc
authors.initials: M
authors.lastname: Cohen
authors.forename: William J
authors.initials: WJ
authors.lastname: French
authors.forename: James
authors.initials: J
authors.lastname: Hoekstra
authors.forename: Sunil V
authors.initials: SV
authors.lastname: Rao
authors.forename: Witold
authors.initials: W
authors.lastname: Ruzyllo
authors.forename: Juan M
authors.initials: JM
authors.lastname: Ruiz-Nodar
authors.forename: Manel
authors.initials: M
authors.lastname: Sabaté
authors.forename: Petr
authors.initials: P
authors.lastname: Widimsky
authors.forename: Robert Gabor
authors.initials: RG
authors.lastname: Kiss
authors.forename: Jose Luis
authors.initials: JL
authors.lastname: Navarro Estrada
authors.forename: Hanoch
authors.initials: H
authors.lastname: Hod
authors.forename: Prafulla
authors.initials: P
authors.lastname: Kerkar
authors.forename: Sema
authors.initials: S
authors.lastname: Guneri
authors.forename: Murat
authors.initials: M
authors.lastname: Sezer
authors.forename: Mikhail
authors.initials: M
authors.lastname: Ruda
authors.forename: José Carlos
authors.initials: JC
authors.lastname: Nicolau
authors.forename: Claudio
authors.initials: C
authors.lastname: Cavallini
authors.forename: Iftikhar
authors.initials: I
authors.lastname: Ebrahim
authors.forename: Ivo
authors.initials: I
authors.lastname: Petrov
authors.forename: Jae-Hyung
authors.initials: JH
authors.lastname: Kim
authors.forename: Myung-Ho
authors.initials: MH
authors.lastname: Jeong
authors.forename: Gabriel Arturo
authors.initials: GA
authors.lastname: Ramos Lopez
authors.forename: Peep
authors.initials: P
authors.lastname: Laanmets
authors.forename: Frantisek
authors.initials: F
authors.lastname: Kovar
authors.forename: Christophe
authors.initials: C
authors.lastname: Gaudin
authors.forename: Karen C
authors.initials: KC
authors.lastname: Fanouillere
authors.forename: Pascal
authors.initials: P
authors.lastname: Minini
authors.forename: Elaine B
authors.initials: EB
authors.lastname: Hoffman
authors.forename: Angele
authors.initials: A
authors.lastname: Moryusef
authors.forename: Stephen D
authors.initials: SD
authors.lastname: Wiviott
authors.forename: Marc S
authors.initials: MS
authors.lastname: Sabatine
mesh_terms: D054058:Acute Coronary Syndrome / Q000150:complications / Q000188:drug therapy*; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000925:Anticoagulants / Q000009:adverse effects / Q000627:therapeutic use*; D002423:Cause of Death; D003497:Cyclic N-Oxides / Q000009:adverse effects / Q000627:therapeutic use*; D004311:Double-Blind Method; D000077542:Eptifibatide; D065427:Factor Xa Inhibitors; D005260:Female; D006470:Hemorrhage / Q000139:chemically induced*; D006493:Heparin / Q000627:therapeutic use*; D006801:Humans; D007262:Infusions, Intravenous; D007275:Injections, Intravenous; D008297:Male; D008875:Middle Aged; D009203:Myocardial Infarction / Q000209:etiology / Q000517:prevention & control; D010455:Peptides / Q000627:therapeutic use*; D062645:Percutaneous Coronary Intervention; D019039:Platelet Glycoprotein GPIIb-IIIa Complex / Q000037:antagonists & inhibitors; D011725:Pyridines / Q000009:adverse effects / Q000627:therapeutic use*; D012306:Risk; D016019:Survival Analysis; D016896:Treatment Outcome
chemical_list: D000925:Anticoagulants; D003497:Cyclic N-Oxides; D065427:Factor Xa Inhibitors; D010455:Peptides; D019039:Platelet Glycoprotein GPIIb-IIIa Complex; D011725:Pyridines; D006493:Heparin; D000077542:Eptifibatide; C435830:otamixaban