Aspirin Dose and Ticagrelor Benefit in PLATO: Fact or Fiction?

<i>Objectives:</i> To summarize the available evidence regarding whether or not a higher aspirin maintenance dose inversely affects the ticagrelor benefit observed in the US cohort of the PLATO trial. <i>Background:</i> In the recent PLATO trial, the daily aspirin dosages in the USA were split between 81 and 325 mg while the vast majority of dosing outside of the USA was 75 or 100 mg. The FDA conducted exhaustive analyses of the aspirin dosage in a framework of primary clinical efficacy. Considering the post hoc, not prespecified nature of such analyses as well as multiple confounding problems with biologic plausibility, sensitivity to reclassification of small numbers of cases regarding loading versus maintenance aspirin dosing, and the distribution of events in high-dose aspirin observed outside of the USA, the FDA documents clearly suggest that aspirin dosing does not explain the disparate outcome results. In addition, the Advisory Committee members found no evidence to establish a reasonable link, and they uniformly rejected the hypothesis that aspirin dose affects the heterogeneity of outcomes in PLATO. <i>Methods:</i> Additional evidence dr