We determined the efficacy of abciximab, a platelet glycoprotein IIb/IIIa receptor antagonist, combined with low-dose weight-adjusted heparin in reducing ischemic complications in patients undergoing directional coronary atherectomy (DCA). The Evaluation of IIb/IIIa platelet receptor antagonist 7E3 in Preventing Ischemic Complications (EPIC) trial demonstrated a reduction in the incidence of non-Q-wave myocardial infarction in DCA patients who were treated with abciximab bolus and infusion plus heparin. This benefit, however, was associated with increased bleeding complications. Of the 2,792 patients who had coronary intervention in the Evaluation of PTCA to Improve Long-term Outcome by c7E3 GP IIb/IIIa receptor blockade (EPILOG) trial, 144 (5%) underwent DCA. Patients were randomly assigned to 3 treatment groups: placebo with standard-dose, weight-adjusted heparin; abciximab with low-dose weight-adjusted heparin; or abciximab with standard-dose weight-adjusted heparin. Study end points included 30-day and 6-month composite incidence of death, myocardial infarction, or revascularization. Compared with those undergoing percutaneous transluminal coronary angioplasty (PTCA), DCA patients had a higher rate of myocardial infarction (11.1 % vs 4.9%, p = 0.001) and predominantly non-Q-wave myocardial infarction (9.7% vs 4.4%, p = 0.004). Abciximab was associated with a 57% lower combined rate of death, myocardial infarction, or urgent revascularization within 30 days following DCA (20% placebo vs 8.7% abciximab with low-dose heparin) without excess risk of bleeding complications. A combined analysis of data from the EPIC and EPILOG trials demonstrates a reduction in the rate of death or myocardial infarction (19.9% vs 8.4%, p = 0.008) at 30 days that was sustained for up to 6 months in the abciximab-treated patients. These findings support the premise that non-Q-wave myocardial infarction in DCA patients are platelet mediated.