Prasugrel should not be started in patients likely to undergo urgent CABG. Prasugrel has not been studied in elective PCI, and thus no recommen- dation can be made regarding its use in this clinical setting. Ticagrelor reversibly binds the P2Y12 receptor. Unlike clopidogrel or prasugrel, ticagrelor is not a thienopyridine. It also does not require metabolic conversion to an active metabolite. Compared with clopidogrel in patients with ACS in the PLATO (Platelet Inhibition and Patient Outcomes) trial, ticagrelor was associated with a significant 1.9% reduc- tion in absolute risk and a 16% reduction in relative risk in the primary composite endpoint of vascular death, nonfatal MI, or nonfatal stroke.568 Importantly, a significant reduction in vascular mortality and all-cause mortality was observed. Although CABG-related bleeding was not significantly in- creased with ticagrelor compared with clopidogrel, a signif- icantly greater incidence of major bleeding was observed in patients not undergoing CABG. Ticagrelor was associated with higher rates of transient dyspnea and bradycardia com- pared with clopidogrel, although only a very small percentage of patients discontinued the study drug because of dyspnea. Based on post hoc analysis of the PLATO study, specifically the results in the US patient cohort, a black box warning states that maintenance doses of aspirin above 100 mg reduce the effectiveness of ticagrelor and should be avoided. After any initial dose, ticagrelor should be used with aspirin 75 mg to 100 mg per day.583 Given the twice-daily dosing and reversible nature of the drug, patient compliance may be a particularly important issue to consider and emphasize. Ti- cagrelor has not been studied in elective PCI or in patients who received fibrinolytic therapy; thus, no recommendations about its use in these clinical settings can be made. 5.7.3. IV Antiplatelet Therapy: Recommendations STEMI Class IIa 1. 