Several large RCTs evaluated the impact of GP IIb/IIIa receptor inhibitors in patients with NSTE-ACS who were committed to an invasive strategy.295,296,306 TheACUITY (Acute Catheterization and Urgent Intervention Triage Strategy) trial evaluated unfractionated heparin (UFH) versus bivalirudin with or without GP IIb/IIIa inhibitors.295,307 The rates of composite ischemia (death, MI, unplanned revascularization) in patients who received bivalirudin alone compared with those who received UFH plus GP IIb/IIIa inhibitors were similar (9% ver- Fewer patients experienced major bleeding with bivalirudin alone than did with heparin plus GP IIb/IIIa inhibitors (4% versus 7%; relative risk [RR]: 0.52; 95% confi- The ACUITY Timing trial evaluated the benefit of upstream GP IIb/IIIa receptor antagonist compared with its deferred use, testing the hypothesis that earlier administration of GP IIb/IIIa inhibitors in patients destined for PCI would be superior.308 Composite ischemia at 30 days occurred in 7.9% of patients assigned to deferred use compared with 7.1% assigned to upstream admin- riority; P=0.13 for superiority). Deferred GP IIb/IIIa inhibitors reduced the 30-day rates of major bleeding compared with Similar results were reported by the EARLYACS investigators, who evaluated eptifibatide given upstream versus delayed, provisional admin- istration in >9000 patients with NSTE-ACS.295 The compos- ite endpoint of death, MI, recurrent ischemia requiring urgent revascularization, or thrombotic complications occurred in 9.3% of patients in the early-eptifibatide group compared with 10% in the delayed-eptifibatide group (odds ratio [OR]: 0.92; As in the ACUITY Timing trial, the early-eptifibatide group had significantly higher rates of bleeding and red cell transfusions.295,308 Amsterdam et al 2014 AHA/ACC NSTE-ACS Guideline e367 4.3.2. 