A post hoc analysis suggested there were 3 subgroups of ACS patients who did not have a favorable net clinical benefit (defined as the rate of death due to any cause, nonfatal MI, nonfatal stroke, or non CABG-related nonfatal TIMI major bleeding) from the use of prasugrel or who had net harm: Patients with a history of stroke or transient ischemic attack before enrollment had net harm from prasugrel (HR: 1.54; no net benefit from prasugrel (HR: 0.99; 95% CI: 0.81 to 1.21; P 0.92); and patients with a body weight of 60 kg had no net benefit from prasugrel (HR: 1.03; 95% CI: 0.69 to 1.53; P 0.89). In both treatment groups, patients with at least 1 of these risk factors had higher rates of bleeding than those The FDA approved prasugrel on July 10, 2009, and cited a contraindication against its use in patients with a history of transient ischemic attack or stroke or with active pathological bleeding.8 The FDA labeling information includes a general warning against the use of prasugrel in patients age 75 years because of concerns of an increased risk of fatal and intra- cranial bleeding and uncertain benefit except in high-risk situations (patients with diabetes or a history of prior MI), in which case the net benefit appears to be greater and its use may be considered.8 In focusing specifically on pa- tients with UA/NSTEMI, the rate of the primary efficacy endpoint was significantly reduced in favor of prasugrel The pivotal trial for ticagrelor, PLATO (Study of Platelet Inhibition and Patient Outcomes),9 was a multi- center, international, randomized controlled trial compar- ing ticagrelor with clopidogrel (on a background of aspirin therapy) to determine whether ticagrelor is superior to clopidogrel for the prevention of vascular events and death in a broad population of patients with ACS (see Online Data Supplement). 