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. Of note, subgroup analysis consistently showed the same aspirin-dose effect outside the United States. With- out being able to fully rule out the play of chance or other factors related to clinical care in North America as explana- tions for the regional interaction, PLATO concluded that a low aspirin maintenance dose ( 100 mg daily) is likely to be associated with the most favorable outcomes when using the potent P2Y12 inhibitor ticagrelor in patients with ACS.11 Because of its reversible inhibition of the P2Y12 receptor, ticagrelor is associated with more rapid functional recovery of circulating platelets and, consequently, a faster offset of effect than clopidogrel. Although this may represent a poten- tial advantage for patients with ACS undergoing early CABG, it may theoretically pose a problem for noncompliant patients (especially given its twice-daily dosing regimen). The FDA approved ticagrelor on July 20, 2011.12 The FDA also issued a Boxed Warning indicating that aspirin daily maintenance doses of 100 mg decrease the effec- tiveness of ticagrelor, cautioned against its use in patients with active bleeding or a history of intracranial hemor- rhage, and advocated a Risk Evaluation and Mitigation Strategy, a plan to help ensure that the benefits of ticagrelor outweigh its risks. As part of that plan, the manufacturer is mandated to conduct educational outreach programs to alert physicians about the risk of using higher doses of aspirin. 