Randomized Evaluation of the Safety and Efficacy of Enoxaparin Versus Unfractionated Heparin in High-Risk Patients With Non-ST-Segment Elevation Acute Coronary Syndromes Receiving the Glycoprotein IIb/IIIa Inhibitor Eptifibatide

Abstract

Background-Current pharmacotherapeutic options for high-risk non-ST-segment elevation acute coronary syndrome patients include aspirin, clopidogrel, heparin, and platelet glycoprotein IIb/IIIa inhibition. A key issue of uncertainty is the safety and efficacy of combination glycoprotein IIb/IIIa inhibitor and low-molecular-weight heparin therapy. Methods and Results-We randomized 746 patients with rest ischemic discomfort within 24 hours after the onset of symptoms and ST-segment deviation and/or elevation of serum cardiac markers to receive open-label enoxaparin (1 mg/kg subcutaneously twice daily) or unfractionated heparin (70-U/kg bolus; 15 U · kg Ϫ1 · h Ϫ1 infusion, titrated to an activated partial thromboplastin time of 1.5 to 2 times control) for 48 hours. All patients received aspirin and eptifibatide (180-g/kg bolus; 2 g · kg Ϫ1 · min Ϫ1 infusion). Major non-coronary artery bypass surgery-related bleeding at 96 hours (primary safety outcome) was significantly lower among enoxaparin-treated patients than among heparin-treated patients (1.8% versus 4.6%, Pϭ0.03). Minor bleeding was more frequent in the enoxaparin group (30.3% versus 20.8%, Pϭ0.003). Patients in the enoxaparin group were less likely to experience ischemia as detected by continuous ECG evaluation (primary efficacy outcome) during the initial (14.3% versus 25.4%, Pϭ0.0002) and subsequent (12.7% versus 25.9%, PϽ0.0001) 48-hour monitoring periods. Death or myocardial infarction at 30 days was significantly lower in the enoxaparin group (5% versus 9%, Pϭ0.031). Conclusions-When aspirin and eptifibatide are used in high-risk non-ST-segment elevation acute coronary syndrome patients, enoxaparin improves outcomes (determined on the basis of better safety and efficacy) compared with currently recommended unfractionated heparin therapy and provides a useful novel alternative therapeutic strategy.

The impact of bleeding in patients with acute coronary syndromes: How to optimize the benefits of treatment and minimize the risk

“…Earlier trials (ESSENCE [24], TIMI 11B [19] and INTERACT [25]) showed that enoxaparin resulted in improved clinical outcomes, with no increase or even a reduction in bleeding (25). In contrast, the recent SYNERGY trial (7) showed no benefit, but rather a 17% increase in major bleeding, in patients receiving enoxaparin.…”

Application of Current Guidelines to the Management of Unstable Angina and Non-ST-Elevation Myocardial Infarction

“…38,42 Importantly, enoxaparin was compared with UFH in 746 patients with UA/NSTEMI receiving aspirin and eptifibatide in the Integrilin and Enoxaparin Randomized Assessment of Acute Coronary Syndrome Treatment (INTERACT) trial. 43 The primary endpoint, non-CABG-associated major bleeding, was significantly lower in the enoxaparin compared to the UFH groups (1.8% versus 4.6%), although the relative incidence of minor bleeding was reversed. Also, the rate of death or nonfatal MI at 30 days and of ischemia on a continuous Holter monitor were each reduced almost by half in the enoxaparin group.…”

First experience with direct, selective factor Xa inhibition in patients with non-ST-elevation acute coronary syndromes: results of the XaNADU-ACS Trial

“…Ischemia on ST-monitoring has been established as an important risk marker in patients with non-ST-elevation ACS [16][17][18][19]. In addition, reductions in Factor Xa inhibition in acute coronary syndromes 445 asymptomatic ischemia have been associated with reductions in other clinically important endpoints [20,21] and have been used to identify patients who benefit from potent or prolonged antithrombotic therapy [22]. In this small sample, differences in baseline characteristics (e.g.…”