TAO trial: Otamixaban without advantages as the only anticoagulant in acute coronary syndromes

Despite progress in antiplatelet, anticoagulant therapy and invasive strategy, patients with non-ST-segment elevation acute coronary syndrome present an elevated risk of events. There is no consensus on the use of a single anticoagulant which can be administered in the Coronary Unit and also at the time of coronary intervention.

The anticoagulant direct factor Xa inhibitor, Otamixaban, inhibits the generation of thrombin with rapid onset and offset,  linear pharmacokinetics, predictable response and limited renal elimination which makes it an attractive option for use with non-ST-segment elevation acute coronary syndrome. The purpose of the study was to compare the safety and efficacy of otamixaban vs unfractionated heparin plus eptifibatide in patients with non-ST-segment elevation acute coronary syndrome and invasive strategy. It was a double-blind, randomized controlled superiority study which randomized 13,229 patients to otamixaban vs unfractionated heparin plus eptifibatide at the time of intervention. The primary efficacy endpoint was combined death and infarction at 7 days that resulted in 5.5% of the otamixaban group vs 5.7% of the heparin/eptifibatide group (p=0.93). The primary safety endpoint of major or minor bleeding according to TIMI criteria was higher in the otamixaban group (3.1% vs 1.5%, p<0.001). The outcomes were consistent in all the prespecified groups.

Conclusion: 

Otamixaban does not reduce the incidence of ischemic events and increased bleeding in comparison with heparin plus eptifibatide in patients with non-ST-segment elevation acute coronary syndrome who received invasive strategy.

Editorial comment:

Otamixaban will be discontinued given the results of this work. Other works with new anticoagulants also failed to show positive outcomes with non-ST-segment elevation acute coronary syndrome which would indicate that the antiplatelet aggregation plays a more important role than the anticoagulant in this scenario. 

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Original title: Anticoagulation With Otamixaban and Ischemic Events in Non–ST-Segment Elevation Acute Coronary Syndromes The TAO Randomized Clinical Trial.