Abstract 14192: Effect of Aspirin Dosing in Patients Treated With P2Y12 Inhibitors for Secondary Prevention of Cardiovascular Events

Background: The ADAPTABLE was a pragmatic randomized controlled trial that found no difference between high dose vs low dose aspirin for secondary prevention of ischemic or bleeding events. Whether concomitant P2Y12 inhibitor therapy modifies the effect of aspirin dose on clinical events remains unclear. Methods: Participants in ADAPTABLE were stratified according to baseline use of clopidogrel or prasugrel (P2Y12 group). Ticagrelor was not permitted due to a black box warning with high dose aspirin. The primary effectiveness endpoint was a composite of myocardial infarction, stroke, or death and the primary safety endpoint was hospitalization for major bleeding. We used multivariable Cox regression to compare the relative effectiveness and safety of aspirin dose within P2Y12 and non-P2Y12 groups. Results: Of the 13,815 (91.6%) participants with available data, 3,051 (22.1%) were on a P2Y12 inhibitor at baseline (clopidogrel: 93.4%; prasugrel: 6.6%). P2Y12 inhibitor use was associated with higher risk of the primary effectiveness endpoint (10.86% vs. 6.31%; adjusted HR 1.44 95% CI 1.22-1.62) but was not associated with bleeding (0.53% vs. 0.95%; adjusted HR:1.42; 95% CI 0.91, 2.22). We found no interaction in the relative effectiveness and safety of high vs. low dose aspirin by P2Y12 inhibitor use (Table, P interaction 0.09 and 0.73 for primary effectiveness and safety endpoint, respectively). Aspirin dose switching and discontinuation occurred in 28.6% of patients. Although this was more common in high dose vs. low dose aspirin, the above rates did not differ between the P2Y12 and non-P2Y12 groups. Conclusion: In this pre-specified subgroup analysis of a large, pragmatic trial, we found that the relative effectiveness and safety of high dose vs. low dose aspirin was not modified by baseline use of P2Y12 inhibitors. Decisions regarding aspirin dosing should be individualized based on clinical factors and patient preference, regardless of P2Y12 inhibitor use.