In a study presented at the 58th annual Scientific Sessions of the American College of Cardiology and simultaneously published by The New England Journal of Medicine, researchers reported that a strategy using an upstream, investigational dose of INTEGRILIN(R) (eptifibatide) routinely in patients with Acute Coronary Syndrome (ACS), at least 12 hours prior to angiography, failed to achieve either the primary or secondary endpoints of the trial. Significantly higher rates of bleeding and transfusions also were reported.

"These results do not support the upstream use of double-bolus plus infusion eptifibatide as a routine course of treatment in ACS," said Enrico Veltri, M.D., group vice president of global clinical research, cardiovascular and metabolic disease, Schering-Plough Research Institute. "However, the results do not change what other studies have previously reported: that eptifibatide remains an integral component of therapy for appropriate patients undergoing PCI."

L. Kristin Newby, MD, associate professor of medicine at Duke Clinical Research Institute, presented the results of the nearly 9,500-patient Early Glycoprotein IIb-IIIa Inhibition in Non-ST-Segment Elevation Acute Coronary Syndrome (EARLY ACS) study, which was designed to determine whether routine early use of eptifibatide would result in improved cardiovascular outcomes for patients with ACS compared to delayed provisional use. The primary efficacy endpoint was a composite of death, (re)infarction (MI), recurrent ischemia requiring urgent revascularization, or thrombotic bailout through 96 hours. The secondary endpoint was death or (re)MI at 30 days. Safety endpoints included bleeding and transfusions through 120 hours.

No statistical difference was observed between the groups in either the primary or secondary endpoints. The primary endpoint occurred in 9.3 percent of the study group (receiving double-bolus plus infusion early administration of eptifibatide 12 or more hours prior to angiography), compared with 10.0 percent of the delayed provisional group (p=0.23). At 30 days, the death or (re)MI rate for the study group was 11.2 percent compared to 12.3 percent for the delayed provisional group (p=0.079).

Significantly higher rates of bleeding were observed in the study group, with 118 patients experiencing a TIMI major bleeding event, compared to 83 in the delayed provisional group (p=0.015). Investigators reported a 7.6 percent vs. 5.1 percent rate of moderate or severe bleeding (p Within the trial, the single largest group was PCI patients (n=5,559). An analysis of those randomized to receive early eptifibatide showed that these patients experienced fewer primary and secondary composite events after PCI than those randomized to the delayed provisional eptifibatide strategy.

"Consistent with findings from prior trials, in this double-bolus study, NSTE ACS patients undergoing PCI experienced fewer post-PCI ischemic complications with early eptifibatide," said Robert Giugliano, MD, lead author of the EARLY ACS study, associate physician at Brigham and Women's Hospital and associate professor at Harvard Medical School.

EARLY ACS Study Design

EARLY ACS randomly allocated 9,492 patients with high-risk non-ST-segment elevation ACS to one of two strategies: early routine eptifibatide, or early placebo with delayed provisional eptifibatide commenced after angiography but pre-PCI. After randomization, patients received double-blinded early eptifibatide (180 mcg/kg intravenous double bolus [10 minutes apart] and 2.0 mcg/kg/min [1.0 mcg/kg/min if creatinine clearance