Anticoagulation With Otamixaban and Ischemic Events in Non–ST-Segment Elevation Acute Coronary Syndromes

Abstract

IMPORTANCE 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. DESIGN, SETTING, AND PARTICIPANTS 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.INTERVENTIONS 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. MAIN OUTCOMES AND MEASURESThe 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 AND RELEVANCE 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.

Anticoagulation for percutaneous coronary intervention

“…The study showed that otamixaban was associated with increased bleeding risk without a reduction in ischemic events [45].…”

Antithrombotic management in patients with percutaneous coronary intervention requiring oral anticoagulation

“…In the TAO trial [16], 13,229 patients were randomized either to a bolus of otamixaban, a synthetic intravenous direct factor Xa inhibitor, followed by one of two infusion doses of 0.100 or 0.140 mg/kg/h or to UFH plus eptifibatide, at the time of PCI. The final otamixaban infusion rate selected after interim analysis was 0.140 mg/kg/h.…”

“…A high risk of major bleeding with triple therapy in AF patients was also confirmed after acute MI [25] and following MI and coronary intervention [16]. In 40 812 patients from the Danish nationwide registry during a mean follow-up of 477 days, 4.6% of patients were admitted to hospital due to bleeding complications [22].…”

Direkt orális antikoagulánsok a kardiológiában

“…Osztály-hatás szintjén elmondható, hogy ebben az indikációban a DOAC-ok a vérzésveszélyt fokozzák és a mortalitást nem befolyásolják [6]. Intravénás alkalmazásuk nem előnyö-sebb a hagyományos szereknél (heparin és glikoprotein IIb/IIIa) [7]. Az akut coronariaszindróma utáni szakaszban alkalmazott ultra kis adagú rivaroxaban azonban ér-dekes módon hatékonynak bizonyult a kettős vérle-mezkegátló kezeléssel kombinált módon alkalmazva [8].…”