Preferred options are eptifiba- tide or tirofiban.43,94,295 (Level of Evidence: B) Despite the large number of new antiplatelet and antithrombotic agents, aspirin, which targets COX and subsequent throm- inhibition, is the mainstay of antiplatelet therapy. Multiple other pathways of platelet activation can be targeted by agents that inhibit the platelet P2Y12 receptor, including thi- enopyridine prodrug agents, such as clopidogrel and prasugrel, which require conversion into molecules that bind irreversibly to the P2Y12 receptor.Additional pyrimidine derivatives, includ- ing ticagrelor, do not require biotransformation and bind revers- ibly to the P2Y12 receptor, antagonizing adenosine diphosphate platelet activation. In addition to these oral agents, intravenous GP IIb/IIIa receptor inhibitors, including abciximab, eptifiba- tide, and tirofiban, target the final common pathway of platelet aggregation. In the EARLY ACS (Early Glycoprotein IIb/IIIa Inhibition in Patients With Non ST-Segment Elevation Acute Coronary Syndrome) trial, patients were randomly assigned to either early, pre PCI double-bolus eptifibatide or delayed, provisional eptifibatide. Seventy-five percent of the patients received upstream, preprocedure clopidogrel. The risk of TIMI major bleeding in the early eptifibatide group was 2.6% com- pared with 1.8% (P=0.02) in the delayed provisional group.295 In the GUSTO IV-ACS (Global Use of Strategies To Open Occluded Coronary Arteries IV-Acute Coronary Syndromes) trial, there was no clinical benefit of abciximab in this popu- lation; in troponin-negative patients, mortality was 8.5% com- pared with 5.8% in controls (P=0.002).288,289,296,297 Aspirin is the established first-line therapy in patients with NSTE-ACS and reduces the incidence of recurrent MI and A loading dose of non enteric-coated aspirin 162 mg to 325 mg is the initial antiplatelet therapy. 