Integrilin to Minimise Platelet Aggregation and Coronary Thrombus - II - IMPACT II

Description:

Eptifibatide for death, MI and revascularization in percutaneous intervention.

Hypothesis:

To evaluate whether inhibition of the platelet IIb/IIIa integrin with eptifibatide (integrilin) can prevent complications of percutaneous coronary intervention.

Study Design

Study Design:

Patients Screened: Not given
Patients Enrolled: 4,010
Mean Follow Up: 6 months
Mean Patient Age: 61
Female: 25

Patient Populations:

Patients scheduled for elective, urgent, or emergent coronary intervention with an FDA approved device (balloon angioplasty, directional atherectomy, rotational atherectomy, excimer laser ablation)

Exclusions:

History of bleeding diathesis
Severe hypertension (Systolic BP > 200 or diastolic BP > 100 mmHg)
Major surgery within previous 6 weeks
History of stroke or CNS disorders
Pregnancy
Gastrointestinal or genitourinary bleeding within previous 30 days
Other major illness

Primary Endpoints:

Composite of death, myocardial infarction, unplanned surgical or repeat percutaneous revascularization, or stent placement for abrupt closure.
Major bleeding

Secondary Endpoints:

Occurrence of the composite endpoint at the completion of drug infusion (24 h) and at 6 months
Composite endpoint as determined by the site principal investigators (rather than the Clinical Events Committee)
Outcomes by risk stratification and actual treatment received
Frequency of angiographically documented abrupt closure

Drug/Procedures Used:

Eptifibatide, 135 mcg/kg bolus followed by 0.5 mcg/kg/min x 24 hours; Eptifibatide, 135 mcg/kg bolus followed by 0.75 mcg/kg/min x 24 hours, or placebo

Concomitant Medications:

Aspirin, heparin

Principal Findings:

By 30 days, the composite endpoint had occurred in 151 (11.4%) patients in the placebo group compared with 124 (9.2%) in the 135/0.5 eptifibatide group (p=0.063) and 132 (9.9%) in the eptifibatide 135/0.75 group (p=0.22).

By treatment-received analysis, the 135/0.5 regimen produced a significant reduction in the composite endpoint (11.6 vs 9.1%, p=0.035), but the 135/0.75 regimen produced a less substantial reduction (11.6 vs 10.0%, p=0.18).

At 6 months, the composite event rate was 30.2% for patients receiving eptifibatide compared to 31.5% for patients receiving placebo (odds ratio 0.94, 95% CI, 0.82 to 1.08).

Eptifibatide treatment did not increase rates of major bleeding or transfusion.

Interpretation:

The modest benefit over aspirin achieved by eptifibatide in IMPACT II suggested that higher eptifibatide doses would be needed to match the degree of platelet inhibition seen with abciximab. Animal models of abciximab in acute coronary syndromes indicated that optimal arterial perfusion required 80% receptor occupancy by the antibody. The doses of eptifibatide used in the IMPACT II study achieved 50-60% inhibition by standard measures. This rationale led to a doubling of the eptifibatide dose for the PURSUIT trial.

References:

1. Lancet 1997;349:1422-8. Final results

Clinical Topics: Acute Coronary Syndromes, Cardiac Surgery, Invasive Cardiovascular Angiography and Intervention, Aortic Surgery, Interventions and ACS

Keywords: Odds Ratio, Myocardial Infarction, Acute Coronary Syndrome, Platelet Aggregation Inhibitors, Atherectomy, Coronary, Peptides, Lasers, Excimer, Percutaneous Coronary Intervention, Platelet Glycoprotein GPIIb-IIIa Complex


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