Contemporary clinical trials have therefore been needed to define the optimal timing of initiation of GP IIb/IIIa inhibitor therapy in patients with UA/NSTEMI, whether upstream (at presentation and before angiography) or deferred (at the time of angiography/PCI), and its optimal application (whether routine, selective, or provisional) and to clarify the relative benefit and risk of GP IIb/IIIa inhibitor therapy as a third antiplatelet agent in combination with aspirin and a thienopyridine. The EARLY ACS (Early Glycoprotein IIb/IIIa Inhibition in Patients With Non ST-Segment Elevation Acute Coronary Syndrome) trial56 tested the hypothesis that a strategy of early routine administration of the GP IIb/IIIa inhibitor eptifibatide would be superior to delayed provisional administration in reducing ischemic complications among high-risk patients with UA/NSTEMI. The study investigators enrolled 9492 patients who presented within 24 hours of an episode of ischemic rest discomfort of at least 10 minutes duration. The study subjects were randomized within 8 to 12 hours after presentation and assigned to an invasive treatment strategy no sooner than the next calendar day. To qualify as having high-risk UA/NSTEMI, the subjects were required to have at least 2 of the following: ST-segment depression or transient ST-segment elevation, elevated biomarker levels (creatine kinase myocardial band or troponin), or age 60 years. The study subjects were randomized in a double-blind design to receive either early routine administration of eptifibatide (double bolus followed by standard infusion) or delayed provisional eptifibatide at the time of PCI. Eptifibatide infusion was given for 18 to 24 hours after PCI in both groups. For patients who underwent PCI, the total duration of the infusion was 96 hours. For patients who did not receive PCI for whatever reason, the duration of infusion was 96 hours. The study infusion was stopped 2 hours before surgery for those undergoing CABG. 