Patients with a history of bleeding were excluded in PLATO, and 4% of patients had a prior history of nonhemorrhagic stroke.9 The efficacy and safety of ticagrelor in patients with prior tran- sient ischemic attack or stroke were not reported in PLATO,9 and the balance of risks and benefits of ticagrelor in this patient population remains unclear. A separate analysis was performed for the 5216 patients in PLATO admitted with ACS and prespecified as planned for noninvasive management (constituting 28% of the overall PLATO study population).10 Compared with clopidogrel, ticagrelor was associated with a lower incidence of the 0.73 to 1.00; P 0.04) and overall mortality without increas- ing major bleeding. These results indicate the benefits of intensified P2Y12 inhibition with ticagrelor applied broadly for patients regardless of the intended or actualized manage- The benefits of ticagrelor in PLATO appeared to be attenuated in patients weighing less than the median weight for their sex and those not taking lipid-lowering therapies at randomization.9 There was a significant interaction between treatment and geographic region, with patients enrolled in North America having no statistically significant differences between ticagrelor and clopidogrel with respect to the pri- mary efficacy endpoint.9 Extensive additional analyses were conducted to explore potential explanations for this interac- tion between treatment effect in PLATO and geographic region and whether this could be explained by specific patient characteristics or concomitant therapies.11 Mahaffey and colleagues11 noted that a significantly higher proportion of patients in the United States received a median aspirin dose of 300 mg daily compared with the rest of the world (53.6% versus 1.7%). Indeed, of all 37 baseline and postrandomiza- tion variables explored, only aspirin maintenance dose ap- peared to explain a substantial fraction of the regional interaction. 