Evaluation of c7E3 for the Prevention of Ischemic Complications - EPIC

Description:

Abciximab for death, MI, and revascularization in percutaneous intervention.

Hypothesis:

A chimeric monoclonal antibody Fab fragment (c7E3 Fab) directed against the platelet glycoprotein IIb/IIIa receptor will reduce the occurrence of ischemic complications.

Study Design

Study Design:

Patients Screened: Not given
Patients Enrolled: 2,099
Mean Follow Up: 30 days; 6 months
Mean Patient Age: 61
Female: 28

Patient Populations:

Acute evolving myocardial infarction (MI) within 12 hours after the onset of symptoms that necessitated direct or "rescue" percutaneous intervention; or
Early postinfarction angina or unstable angina with at least 2 episodes of angina at rest associated with changes on resting electrocardiography during the previous 24 hours, despite medical therapy; or
Clinical or angiographic characteristics indicating high risk according to modified American Heart Association or American College of Cardiology criteria.

Exclusions:

Age > 80 years
Known bleeding diathesis
Major surgery within preceding 6 weeks
Stroke within preceding 2 years

Primary Endpoints:

A prespecified composite of any of the following events in the first 30 days after randomization:
Death from any cause
Nonfatal MI
Coronary-artery bypass grafting or repeat percutaneous intervention for acute ischemia
Insertion of a coronary endovascular stent because of procedural failure or placement of an intra-aortic balloon pump to relieve refractory ischemia
Unplanned repeat angioplasty to treat recurrent ischemia
Urgent coronary surgery to treat recurrent ischemia or failure of an angioplasty
Placement of an intracoronary stent to treat imminent or complete abrupt closure of the vessel undergoing angioplasty
Placement of an intra-aortic balloon pump for recurrent ischemia when a repeat revascularization procedure was contraindicated
Bleeding events, classified as major, minor, or insignificant

Secondary Endpoints:

Bleeding events, classified as major, minor, or insignificant

Drug/Procedures Used:

Three treatment groups (double blind):
c7E3 Fab in a bolus dose of 0.25 mg per kg of body weight, followed by an infusion of 10 mg per minute
c7E3 Fab in a bolus dose of 0.25 mg per kg of body weight, followed by a placebo infusion
Placebo bolus and placebo infusion

Concomitant Medications:

All patients:
Aspirin, 325 mg oral at least 2 hours before angioplasty or atherectomy, daily thereafter

Heparin
During procedure, intravenous, initial bolus dose of 10,000 to 12,000 units, followed by incremental bolus doses of up to 3,000 units at 15-minute intervals; no more than 20,000 units during the procedure. Goal was to keep activated clotting time between 300 and 350 seconds during operation.
Continued by constant infusion for at least 12 hours to maintain activated partial-thromboplastin time at 1.5 to 2.5 times control value.

Aspirin at discharge, 325 mg/day (required)

Principal Findings:

30 days:
As compared with placebo, c7E3 Fab bolus and infusion resulted in a 35% reduction in the rate of the primary end point (12.8 vs 8.3%, p = 0.008). This result was consistent across the end points of unplanned revascularization procedures and nonfatal MI.
A 10% reduction was observed with c7E3 bolus alone (12.8% vs 11.5%, p = 0.43).
Bleeding events and transfusions were more frequent in the c7E3 Fab bolus and infusion group than in the other two groups.

6 months:
The absolute difference in patients with a major ischemic event or elective revascularization was 8.1% between placebo bolus/placebo infusion patients and c7E3 bolus/c7E3 infusion patients (35.1% vs 27.0%; 23% reduction, p = 0.001).
The favorable effect was mainly attributed to the need for less bypass surgery or repeat angioplasty in patients with an initially successful procedure.

3 years:
Composite end points occurred in 41.1% of those receiving abciximab bolus plus infusion; 47.4% of those receiving abciximab bolus only; and 47.2% of those receiving placebo only (for abciximab bolus plus infusion vs placebo, P=0.009).

Interpretation:

Ischemic complications of coronary angioplasty and atherectomy were reduced with a monoclonal antibody directed against the platelet IIb/IIIa glycoprotein receptor, although the risk of bleeding was increased. Abciximab bolus with infusion given at the time of coronary angioplasty improves outcomes as long as 3 years after the procedure.

References:

1. N Engl J Med 1994;330:956-61. Design and baseline results.
2. Lancet 1994;343:881-6. 6-month results
3. Am J Cardiol 1996;77:1045-51. 6-month results
4. JAMA 1997;278:479-84. 3-year outcomes

Clinical Topics: Cardiac Surgery, Invasive Cardiovascular Angiography and Intervention, Aortic Surgery

Keywords: Myocardial Infarction, Platelet Aggregation Inhibitors, Atherectomy, Body Weight, Blood Platelets, Electrocardiography, Immunoglobulin Fab Fragments, Angioplasty, Platelet Membrane Glycoproteins


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