In a subgroup analysis, early administration of eptifibatide in patients who underwent PCI was associated with numerically fewer ischemic events. A second contemporary study, the ACUITY (Acute Cath- eterization and Urgent Intervention Triage Strategy) trial,57 examined in part the optimal strategy for the use of GP IIb/IIIa inhibitors in moderate- and high-risk ACS patients undergoing early invasive therapy. A total of 9207 patients were randomized to 1 of 3 antithrombin regimens: unfractionated heparin (UFH) or enoxaparin plus GP IIb/IIIa inhibitor therapy; bivalirudin plus GP IIb/IIIa inhibitor therapy; or bivalirudin alone. Patients assigned to the heparin (UFH or enoxaparin) plus GP IIb/IIIa inhibitor therapy or to the bivalirudin plus GP IIb/IIIa inhibitor therapy were also randomized to immediate upstream routine GP IIb/IIIa inhibitor therapy or deferred selective use of GP IIb/IIIa inhibitor therapy at the time of PCI. A clopidogrel loading dose of 300 mg was required in all cases no later than 2 hours after PCI, and provisional GP IIb/IIIa inhibitor use was permitted before angiography in the deferred group for severe breakthrough ischemia. The composite ischemic endpoint oc- curred in 7.1% of the patients assigned to upstream administra- tion and in 7.9% of patients assigned to deferred selective thus the noninferiority hypothesis was not achieved. Major bleeding was lower in the deferred-use group versus the up- stream group (4.9% to 6.1%; P 0.001 for noninferiority and P 0.009 for superiority). Although early GP IIb/IIIa inhibitor therapy as dual antiplatelet therapy also reduced complications after PCI, supporting its continued role in patients undergoing PCI,49,53,54,56,58 these 2 most recent studies56,57 more strongly support a strategy of selective rather than routine upstream use of GP IIb/IIIa inhibitor therapy as part of triple antiplate- let therapy. 