Elsevier

American Heart Journal

Volume 151, Issue 2, February 2006, Pages 373-379
American Heart Journal

Clinical Investigation
Acute Ischemic Heart Disease
Randomized evaluation of the 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. Long-term results of the Integrilin and Enoxaparin Randomized Assessment of Acute Coronary Syndrome Treatment (INTERACT) trial

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Background

Patients with high-risk non–ST-segment elevation acute coronary syndromes (NSTE ACS) benefit from the early administration of aspirin, a small molecule glycoprotein IIb/IIIa inhibitor such as eptifibatide, and heparin. The INTERACT trial demonstrated that in high-risk patients with ACS receiving aspirin and eptifibatide, the use of enoxaparin compared with unfractionated heparin (UFH) was associated with less bleeding, less early myocardial ischemia, and improved 30-day outcomes.

Objective

The aim of our study was to determine whether the short-term benefits of enoxaparin compared with UFH observed in high-risk patients with NSTE ACS are maintained over a prolonged period of follow-up.

Methods

Six hundred thirty-nine patients that were representative of the total population of subjects in the INTERACT trial were followed up for a median period of 2.5 years.

Results

In this group, the early benefit of enoxaparin was maintained. The incidence of death or myocardial infarction at the time of long-term follow-up was 39% lower in patients receiving enoxaparin compared with those who received UFH (8.9% vs 14.7%, P = .024). There was no difference in the frequency of cardiac catheterization in the groups receiving either enoxaparin or UFH.

Conclusions

The early treatment of high-risk patients with NSTE ACS receiving aspirin and eptifibatide with enoxaparin is associated with early outcome benefits that are sustained over a prolonged follow-up period. This trial supports the concept that early treatment directed against platelet and thrombin formation is associated with better short- and long-term outcomes.

Section snippets

Patient group

The entry criteria for enrollment, the study design, treatment protocol, and end point definitions have been described previously.6 The INTERACT trial randomized 746 patients at 50 centers in Canada, with rest ischemic symptoms within the past 24 hours. In addition, patients had ST-segment deviation (ST depression >0.1 mV or transient ST-segment elevation) and/or elevated serum biomarkers (troponin I or T >3× the upper reference level or creatine kinase–MB [CK-MB] greater than normal). Written

Short-term outcome

As reported previously,6 patients randomized to receive enoxaparin had a significantly lower 30-day incidence of death or MI compared with those receiving UFH (5% vs 9%, P = .031). There was also a trend to a lower composite end point of death, MI, or recurrent angina in patients with adjudicated ECG changes in the enoxaparin-treated group (9% vs 12.6%, P = .11).

Long-term follow-up

Of the 746 patients enrolled in the trial, 24 died within the 30-day follow-up period. Consequently, there were potentially 722

Discussion

These findings represent the longest term follow-up available to date in a randomized trial comparing enoxaparin and UFH in ACS. The trial demonstrates that when using aspirin and eptifibatide in high-risk patients with NSTE ACS, the early use of enoxaparin is associated with a sustained improvement of long-term clinical outcomes, including death or MI.

References (15)

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Conflicts of interest: Drs Fitchett, Langer, Armstrong, and Goodman have received research grant support, speaker honoraria, or consultant fees from Aventis Canada, Key Pharmaceuticals, Division of Schering Canada Inc, and Millenium Pharmaceuticals.

d

The INTERACT Trial Long-Term Follow-Up Investigators are listed in the Appendix.

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