• Philippe Gabriel Steg, Shamir R Mehta, Charles V Pollack, Christoph Bode, Marc Cohen, William J French, James Hoekstra, Sunil V Rao, Witold Ruzyllo, Juan M Ruiz-Nodar, Manel Sabaté, Petr Widimsky, Robert Gabor Kiss, Jose Luis Navarro Estrada, Hanoch Hod, Prafulla Kerkar, Sema Guneri, Murat Sezer, Mikhail Ruda, José Carlos Nicolau, Claudio Cavallini, Iftikhar Ebrahim, Ivo Petrov, Jae-Hyung Kim, Myung-Ho Jeong, Gabriel Arturo Ramos Lopez, Peep Laanmets, Frantisek Kovar, Christophe Gaudin, Karen C Fanouillere, Pascal Minini, Elaine B Hoffman, Angele Moryusef, Stephen D Wiviott, Marc S Sabatine, and TAO Investigators.
• Université Paris-Diderot, Sorbonne-Paris Cité, Paris, France. gabriel.steg@bch.aphp.fr
• JAMA. 2013 Sep 18;310(11):1145-55.

ImportanceThe optimal anticoagulant for patients with non-ST-segment elevation acute coronary syndromes (NSTE-ACS) managed with an invasive strategy remains controversial.ObjectiveTo 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.Design, Setting, And ParticipantsRandomized, 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.InterventionsEligible 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.Main Outcomes And MeasuresThe primary efficacy outcome was the composite of all-cause death or new myocardial infarction through day 7.ResultsRates 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 And RelevanceOtamixaban 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.Trial Registrationclinicaltrials.gov Identifier: NCT01076764.

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