The incidence of acute myocardial infarction (AMI) in USA remains significant, approximately 800,000 cases per year [1] . Dual antiplatelet management, including an adenosine diphosphate receptor P2Y ₁₂ inhibitor, is a critical aspect of management of AMI patients undergoing emergency percutaneous coronary intervention (PCI) and in post-AMI management. P2Y ₁₂ inhibitors have been compared in large clinical trials. In the TRITON-TIMI 38 study [2] , prasugrel was compared to clopidogrel in 13,600 ACS patients [2] . Prasugrel treatment significantly reduced a composite of CV death, non-fatal myocardial infarction and non-fatal stroke, albeit with increased major bleeding. In particular, bleeding outcomes were worse if previous stroke or TIA, >75 years of age and weight <60 kg. A separate report on the subset of 3534 STEMI patients undergoing PCI showed similar efficacy results as the overall cohort, but no differences in TIMI major bleeding unrelated to CABG surgery [3] . The PLATO trial [4] randomized >18,000 ACS patients, including 38 % STEMI, to either ticagrelor or clopidogrel [4] . Again, a composite primary endpoint of vascular death, myocardial infarction and stroke was significantly reduced in the ticagrelor arm, including vascular death and overall mortality. The ticagrelor groups also suffered increased major bleeds not related to CABG, including fatal intracranial bleeds ⁴ . Both trials showed reductions in stent thrombosis [24] . Based on these data, the American College of Cardiology (ACC)/American Heart Association (AHA) [5] , the European Society of Cardiology (ESC) [6] , and the Canadian Cardiovascular Society [7] have published guidelines for use of P2Y ₁₂ inhibitors in Acute Coronary Syndromes (ACS) (non-STEMI ACS or STEMI) ( Fig. 1 ) 567 . While the latter 2 bodies have provided strong recommendations for ticagrelor or prasugrel over clopidogrel for use in ACS patients, the ACC/AHA has only indicated that it is “reasonable” for their use with a lower level of evidence (Class 2B) [5] .