Therapeutic use of intravenous eptifibatide in patients undergoing percutaneous coronary intervention: acute coronary syndromes and elective stenting

Abstract

Eptifibatide, a molecule isolated from the venom of the southeastern pygmy rattlesnake, selectively inhibits the platelet receptor IIb/IIIa. The safety and clinical efficacy of eptifibatide in patients undergoing percutaneous coronary intervention (PCI) was first evaluated in the Integrilin to Minimize Platelet Aggregation and Coronary Thrombosis (IMPACT) trial. In this study, the primary combined endpoint (composite of death, myocardial infarction [MI] or target vessel revascularization [TVR] at 30 days) occurred in 9.6% of the patients assigned to eptifibatide bolus followed by the 4-hour infusion versus 12.2% in the placebo group (p = 0.67). In the IMPACT-II trial, two different eptifibatide dosages were studied in 4011 patients undergoing elective PCI. The primary endpoint (death, MI, TVR or stent placement for threatened vessel closure at 30 days) occurred in 11.6% in the placebo group versus 9.1% in the 135/0.5 eptifibatide group (p = 0.035) and 10% in the 135/0.75 eptifibatide group (p = 0.18). The Enhanced Suppression of Platelet IIb/IIIa Receptor with Integrilin Therapy (ESPRIT) trial studied a dose of eptifibatide 3- to 4-fold higher than that used in IMPACT II trial in patients undergoing non-emergent coronary artery stenting (two 180 microg/kg bolus doses 10 minutes apart). The 6-month composite endpoint (death, MI, TVR and 'bailout' eptifibatide use) occurred in 18.3% of patients in the placebo group versus 14.2% in the eptifibatide group (p = 0.008) and was maintained at 12 months (22.1% in the placebo group vs 17.5% in the eptifibatide group, p = 0.0068). The Platelet Glycoprotein IIb/IIIa in Unstable Angina: Receptor Suppression Using Integrilin Therapy (PURSUIT) study in 10 948 patients was designed to study the effect of eptifibatide in the treatment of acute coronary syndromes (ACS) using two different dosages (180 microg/kg bolus followed by an infusion of either 1.3 microg/kg/min or 2 microg/kg/min. The primary endpoint, a composite of death or MI at 30 days, occurred in 15.7% of placebo-treated patients and 14.2% of eptifibatide-treated patients (p = 0.042). This difference was maintained at 7 days (11.6% in the placebo group vs 10.1% in the eptifibatide group, p = 0.016) and at 30 days (15.7% in the placebo group vs 14.2% in the eptifibatide group). In the eptifibatide studies, the rates of major bleeding were 0.7% (0.5% in the control group) in ESPRIT and 2.1% (1.3% in the placebo group) in PURSUIT. The incidence of intracranial bleeding was 0.2% in ESPRIT (0.1% in the placebo group) and 0.7% in PURSUIT (0.8% in the placebo group). Significant thrombocytopenia (platelet count <20 000/microL) was reported in 0.2% of the patients receiving eptifibatide in the ESPRIT trial (0% in the placebo group) and in <1% in PURSUIT (<1% in the placebo group). In summary, several clinical trials have demonstrated a clear-cut reduction in a variety of ischemic events in patients receiving eptifibatide as adjunctive pharmacotherapy during PCI.