Integrilin and Enoxaparin Randomized Assessment of Acute Coronary Syndrome Treatment - INTERACT


The goal of the INTERACT trial was to evaluate the safety and efficacy of unfractionated heparin (UFH) versus the low molecular weight heparin (LMWH) enoxaparin in combination with eptifibatide in treating patients with high-risk non-ST-segment elevation acute coronary syndrome (ACS).

Study Design

Study Design:

Patients Enrolled: 746
Mean Follow Up: 30 days
Mean Patient Age: median age 64
Female: 31

Patient Populations:

>=18 years of age; hospitalized with ischemic chest discomfort of >=10 minute duration occurring at rest and <=24 hours before enrollment; ST-segment depression >=0.1 mV or transient ST-segment elevation >=0.1 mV in >=2 contiguous ECG leads; or elevation of troponin I or T >=3 x ULN, or CKMB > normal.


Uninterpretable ST segment on baseline ECG; ischemia due to an established precipitating cause; cardiogenic shock; scheduled or recent revascularization (CABG <2 months or PCI <6 months); blood pressure >200 mm Hg systolic or >110 mm Hg diastolic; hemoglobin <11 g/dL for men or 9 g/dL for women; thrombocytopenia; ulcerative gastrointestinal disease <6 months; history of cerebral hemorrhage or known intracerebral vascular disease; nonhemorrhagic stroke in previous month; eye, spinal, or central nervous system surgery in previous 2 months; major surgery, organ biopsy, puncture of noncompressible vessel in previous 2 weeks; or known or suspected pregnancy; treatment with abciximab in previous 14 days or with tirofiban or eptifibatide in previous 7 days; allergy or contraindication to aspirin or study drugs; oral anticoagulation treatment in previous 5 days or INR >1.2; fibrinolysis in previous 24 hours; or treatment with investigational agents in previous 30 days; renal failure or other serious disease, including liver failure; or inability to commence ST-segment monitoring <=8 hours after randomization.

Primary Endpoints:

Safety: non-CABG major bleeding at 96 hours
Efficacy: recurrent ischemia detected during continuous ECG monitoring for 96 hours after randomization.

Secondary Endpoints:

Death and nonfatal MI
Death, MI, or recurrent angina (with ECG changes and/or urgent revascularization)

Drug/Procedures Used:

INTERACT included 746 patients with ischemic chest discomfort without ST-segment elevation, all of whom received a 160-mg loading dose of aspirin followed by 80 to 325 mg/day, and the GPIIb/IIIa inhibitor eptifibatide given as a 180-µg/kg IV bolus, followed by 2.0 µg/kg/min as an infusion for 48 hours. Patients were then randomized to treatment with either UFH (n=366) or the LMWH enoxaparin (n=380). All other medications, the decision to proceed with cardiac catheterization, and the use of coronary revascularization wereleft to the discretion of the investigator.

Principal Findings:

The primary safety endpoint, non-CABG major bleeding at 96 hours, occurred less frequently in the enoxaparin arm versus the UFH arm (1.8% vs 4.6%, p=0.03). Major bleeding at 30 days occurred in 8.7% of the UFH arm and 5.3% of the enoxaparin arm (p=0.062). However, minor bleeding at 96 hours occurred more frequently in the enoxaparin arm versus the UFH arm (30.3% vs 20.8%, p=0.003), although there was no difference by 30 days (31.8% vs 24.3%, p=0.22).

Ischemic events by ST-segment monitoring during the first 48 hours occurred in 14.3% of enoxaparin patients versus 25.7% of UFH-treated patients (p=0.0002). Likewise, between 48 and 96 hours, ischemic events by ST segment monitoring occurred in 12.7% of patients in the enoxaparin arm versus 25.9% of patients in the UFH arm (p<0.0001).

The rate of death and nonfatal MI at 30 days was 5.0% in the enoxaparin arm vs 9.0% in the UFH arm (p=0.031). The 30-day composite endpoint of death, MI, or recurrent ischemia with ECG changes occurred in 12.6% of the UFH-treated patients and 9.0% of the enoxaparin recipients (p=0.11).


Among high-risk non-ST-segment elevation ACS patients, treatment with the LMWH enoxaparin in combination with eptifibatide was associated with a lower rate of major bleeding at 96 hours, as well as lower rates of ischemia during and immediately following treatment and lower rates of death or MI at 30 days. The 2002 revision to the ACC/AHA guidelines indicated that data were lacking regarding the efficacy of combining GP IIb/IIIa inhibitors with low molecular weight heparinoids. One day following the release of the guidelines, the results of the INTERACT study shed light on this issue.

Limitations of the study include the fact that it was an open label study and that the time to coronary revascularization was longer (median 101 hours) than that advocated in the recently published TACTICS study (cath between 4 and 48 hours, median 21 hours). Results of the 8,000-patient SYNERGY study which examines the same issue among patients treated with all GP IIb/IIIa inhibitors is pending.


Circulation. 2003;107:238-244.

Clinical Topics: Acute Coronary Syndromes, Anticoagulation Management, Heart Failure and Cardiomyopathies, ACS and Cardiac Biomarkers, Anticoagulation Management and ACS, Heart Failure and Cardiac Biomarkers

Keywords: Depression, Acute Coronary Syndrome, Platelet Aggregation Inhibitors, Cardiac Catheterization, Heparin, Electrocardiography, Platelet Membrane Glycoprotein IIb, Heparinoids, Enoxaparin, Peptides, Troponin I

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