CONCEPT AND CLINICAL-APPLICATION OF PLATELET GLYCOPROTEIN IIB IIIA INHIBITION WITH ABCIXIMAB (C7E3 FAB - REOPRO) FOR THE PREVENTION OF ACUTE ISCHEMIC SYNDROMES/

The platelet membrane glycoprotein (GP) IIb/IIIa integrin receptor is the final common pathway leading to plate let aggregation. Local aggre gation commonly occurs following atherosclerotic plaque rupture or oth er injury to the vascular wall. When GP IIb/IIIa is activated, fibrino gen and von Willebrand factor bind to the receptor with high affinity, crosslinking platelets and locking them to the vessel surface and to each other. This process is central to arterial thrombus formation and consequent acute coronary syndromes, such as myocardial infarction (M I), unstable angina, and abrupt closure following revascularization pr ocedures. Abciximab (c7E3 Fab; ReoPro) is a chimeric monoclonal antibo dy fragment developed specifically to inhibit GP IIb/IIIa receptor act ivity and thus prevent platelet aggregation and thrombosis. Abciximab has been evaluated in several clinical studies, the largest of which w as the Evaluation of Abciximab for the Prevention of Ischemic Complica tions (EPIC) trial. This randomized, multicenter, placebo-controlled t rial enrolled 2,099 patients at high risk for ischemic complications f ollowing coronary revascularization. The patients were randomized into three treatment groups: placebo, abciximab bolus (0.25 mg/kg), or abc iximab bolus plus 12-h infusion (10 mu g/min). Patients in the abcixim ab bolus plus infusion group had significant reductions, compared with placebo, in a composite end point of death, nonfatal MI, and urgent c oronary intervention within 30 days. These positive, short-term findin gs were maintained at 6 months of follow-up. Bleeding complications an d transfusions were significantly increased in abciximab patients, alt hough there was no increase in bleeding-related death, stroke, or surg ery. Retrospective secondary analyses suggested that many of the bleed ing events observed in the EPIC trial may have been associated with co ncomitant high-dose heparin therapy, particularly in lighter weight pa tients. Subsequent clinical trials have shown that bleeding events can be reduced in patients treated with abciximab by using weight-adjuste d heparin dosing without affecting the efficacy of the abciximab bolus plus infusion regimen. Examination of health economic data from the E PIC trial showed that abciximab bolus plus infusion is cost effective as well as clinically beneficial. These results confirm the importance of platelet GP IIb/ma receptor blockade in the treatment of acute thr ombotic syndromes.