Ticagre- lor was also associated with a notable reduction in all-cause mortality in PLATO. Compared with clopidogrel, ticagrelor was associated with a higher rate of non CABG-related major bleeding and slightly more frequent discontinuation of the study drug due to adverse events.9 On the other hand, prasugrel was associated with a significant increase in the rate of TIMI major hemorrhage, TIMI major and non-CABG bleeding, as well as higher fatal and life-threatening bleeding. There was a signifi- cant interaction between the treatment effect in PLATO and the geographic region, with lack of benefit in the United States for ticagrelor versus clopidogrel (with the explanation depending on a post hoc analysis of aspirin maintenance dose, as noted in the preceding text)11 (see Online Data Supplement). It must be recognized, however, that the 2 newer P2Y12 receptor inhibitors were studied in different patient popula- tions and that there is no head-to-head comparative trial of these agents. Also, the loading dose of clopidogrel in TRITON TIMI 38 was lower than is currently recommended in this guideline.7 Furthermore, some emerging studies sug- gest there may be some patients who are resistant to clopi- dogrel, but there is little information about the use of strategies to select patients who might do better with newer P2Y12 receptor inhibitors. Considerations of efficacy in the prevention of thrombosis and risk of an adverse effect related to bleeding and experience with a given medication may best guide decisions about the choice of P2Y12 receptor inhibitor for individual patients14 (Appendix 4). 3.2.3.1.2.1. Timing of Discontinuation of P2Y12 Receptor Inhibitor Therapy for Surgical Procedures. 