Enoxaparin and glycoprotein IIb/IIIa inhibition in non-ST-elevation acute coronary syndrome: insights from the INTERACT trial.

BACKGROUND: Unfractionated heparin (UFH) has been considered the standard anticoagulant for patients with non-ST-segment-elevation acute coronary syndromes (NSTE ACS), yet it has limitations, including an unpredictable dose-response and intravenous administration. Enoxaparin was shown to be more effective than UFH in two large, randomized trials, ESSENCE and TIMI 11B. These trials were conducted before the widespread use of glycoprotein (GP) IIb/IIIa inhibitors, clopidogrel, and an early invasive management strategy, leaving questions concerning whether and how newer agents should be used in combination.

METHODS: The INTERACT trial compared the efficacy and safety of enoxaparin, relative to UFH, in high-risk NSTE ACS patients receiving aspirin and the GP IIb/IIIa inhibitor eptifibatide. The design and primary results of INTERACT are reviewed and compared with similar trials of combination therapy and with observational studies.

RESULTS: In INTERACT, enoxaparin was associated with significant reductions in recurrent ischemia during the first 4 days, death or myocardial infarction at 30 days, and non-coronary artery bypass grafting-related major bleeding at 4 days relative to UFH. Recent trials of enoxaparin in NSTE ACS patients have differed in the use of concomitant medications, the timing and frequency of invasive procedures, and end point definitions. The results from INTERACT are consistent with the results of ESSENCE and TIMI 11B and with "real-world" data from the CRUSADE and GRACE registries.

CONCLUSIONS: In high-risk patients with NSTE ACS, strong consideration should be given to initiation of therapy with aspirin, enoxaparin, a GP IIb/IIIa inhibitor, and clopidogrel while pursuing an early invasive approach.