Early and late clinical outcome following coronary angioplasty performed with platelet glycoprotein IIb/IIIa receptor inhibition: the EPIC Trial results.

Ischemic complications complicate coronary angioplasty in 10-20% of patients. Antithrombotic agents, such as aspirin and heparin, reduce the frequency of peri-procedural complications, but their effect is incomplete. A chimeric (mouse and human) monoclonal antibody (c7E3 Fab) has been developed, which is a specific inhibitor of the platelet glycoprotein IIb/IIIa receptor and prevents platelet-to-platelet aggregation. A randomized study of 2099 patients at "high-risk" for complications after coronary angioplasty has demonstrated a 35% reduction in 30-day ischemic complications resulting from bolus (0.25 mg/kg) and 12-hour infusion (10 micrograms/min) of c7E3 Fab (8.3% in c7E3 Fab-treated patients versus 12.8% in placebo-treated patients; p = 0.008). The highest reduction in ischemic complications was noted in patients presenting with acute myocardial infarction or unstable angina (hazard ratio = 0.5; 95% confidence intervals [CI]: 0.3-0.9) compared with those patients with high-risk anatomy alone (hazard ratio = 0.7; 95% CI: 0.5-1.1). Late (6-month) clinical events were also lower in patients undergoing successful coronary angioplasty (event-free at 48 hours) who treated with bolus and infusion c7E3 Fab (19.2% versus 25.4% in placebo-treated patients; p = 0.007). The beneficial effect of c7E3 Fab on reducing ischemic complications after coronary angioplasty was balanced by a doubling of major bleeding complications in c7E3 Fab-treated patients (14% versus 7% in placebo-treated patients; p = 0.001). Bleeding complications appear to be related to the intensity of peri-procedural anticoagulation using nonweight adjusted heparin. These results suggest that bolus and 12-hour infusion of c7E3 Fab is a valuable pharmacologic adjunct to reduce peri-procedural complications in "high-risk" patients undergoing coronary angioplasty, particularly in those patients with myocardial infarction or unstable angina. Further studies are underway to develop alternative heparin dosing strategies in an effort to reduce the occurrence of bleeding complications associated with c7E3 Fab administration and to assess the benefit of c7E3 Fab-mediated platelet inhibition in lower risk patient subgroups.