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(Circulation. 2003;107:238.)
© 2003 American Heart Association, Inc.

Clinical Investigation and Reports

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

Shaun G. Goodman, MD, MSc; David Fitchett, MD; Paul W. Armstrong, MD; Mary Tan, BSc; Anatoly Langer, MD, MSc, for the Integrilin and Enoxaparin Randomized Assessment of Acute Coronary Syndrome Treatment (INTERACT) Trial Investigators^*

From the Canadian Heart Research Centre and Terrence Donnelly Heart Centre, Division of Cardiology, St Michael’s Hospital, University of Toronto, Toronto, Ontario, Canada (S.G.G., D.F., M.T., A.L.); and the Division of Cardiology, Department of Medicine, University of Alberta, Edmonton, Canada (P.W.A.).

Correspondence to Dr Shaun G. Goodman, St Michael’s Hospital, Division of Cardiology, 30 Bond St, Room 4-072 Queen, Toronto, Ontario, Canada M5B 1W8. E-mail goodmans{at}smh.toronto.on.ca

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^-1 · h^-1 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-µg/kg bolus; 2 µg · kg^-1 · min^-1 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%, P=0.03). Minor bleeding was more frequent in the enoxaparin group (30.3% versus 20.8%, P=0.003). 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%, P=0.0002) and subsequent (12.7% versus 25.9%, P<0.0001) 48-hour monitoring periods. Death or myocardial infarction at 30 days was significantly lower in the enoxaparin group (5% versus 9%, P=0.031).

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.

Key Words: myocardial infarction • angina, unstable • heparin • anticoagulants

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