The following is a summary of “Aspirin Dosing for Secondary Prevention of Atherosclerotic Cardiovascular Disease in Patients Treated With P2Y12 Inhibitors,” published in the October 2023 issue of Cardiology by Girotra et al.

The ADAPTABLE (Aspirin Dosing: A Patient‐Centric Trial Assessing Benefits and Long‐Term Effectiveness) trial, a substantial pragmatic randomized controlled study, concluded that there’s no significant difference between high and low doses of aspirin in the secondary prevention of atherosclerotic cardiovascular disease. However, the impact of concurrent P2Y12 inhibitor therapy on the association between aspirin dose and clinical outcomes remains uncertain.

In this study, participants from ADAPTABLE were categorized based on their initial usage of clopidogrel or prasugrel (P2Y12 group). The primary effectiveness measure comprised a composite of death, myocardial infarction, or stroke, while the primary safety metric was major bleeding necessitating blood transfusions. Using multivariable Cox regression, the investigators assessed and compared aspirin dosages’ relative efficacy and safety within P2Y12 and non‐P2Y12 groups. Among the 13,815 individuals with available data (representing 91.6% of the total cohort), 22.1% were receiving clopidogrel (93.4%) or prasugrel (6.7%) at the outset. Notably, P2Y12 inhibitor use was linked to a heightened risk of the primary effectiveness endpoint (10.86% versus 6.31%; adjusted hazard ratio [HR], 1.40 [95% CI, 1.22–1.62]), yet no significant association was found regarding bleeding incidents (0.95% versus 0.53%; adjusted HR, 1.42 [95% CI, 0.91–2.22]). Importantly, their analysis revealed no relative efficacy and safety interaction between high- and low-dose aspirin in relation to P2Y12 inhibitor use. Although there was a higher frequency of dose alteration or discontinuation in the high-dose aspirin group compared to the low-dose aspirin group overall, this pattern was not altered by P2Y12 inhibitor use.

Their prespecified analysis of the ADAPTABLE trial indicates that the relative effectiveness and safety of high- versus low-dose aspirin remains consistent regardless of baseline P2Y12 inhibitor use.

Source:  ahajournals.org/doi/10.1161/JAHA.123.030385