Comparison of oxidative and tissue stress biomarkers and platelet activation in myocardial infarction treated with prasugrel or ticagrelor

Background Oxidative stress and inflammation are central drivers of platelet activation, endothelial dysfunction, and myocardial injury in acute myocardial infarction (AMI). Redox-sensitive pathways regulate platelet reactivity and vascular inflammation and may interact bidirectionally with P2Y₁₂ inhibition. Circulating biomarkers of oxidative and tissue/inflammatory stress provide insight into these processes and may reflect residual biological risk beyond platelet aggregation. Whether contemporary oral P2Y₁₂ inhibitors differentially modulate these pathways remains incompletely defined. Purpose To compare circulating biomarkers of oxidative stress, tissue stress, and platelet activation in AMI patients undergoing primary percutaneous coronary intervention (pPCI) treated with prasugrel or ticagrelor. Methods This laboratory substudy of a multicentre randomized trial included 476 AMI patients with complete laboratory data (prasugrel n=234; ticagrelor n=242). Baseline demographic, clinical, and procedural characteristics were well balanced between treatment groups (all p> 0.05). Blood samples were obtained 24±6 hours after pPCI. Serum and plasma biomarkers of oxidative stress (thioredoxin-1, 8-isoprostane, superoxide dismutase 3, NADPH oxidase 2), tissue/inflammatory stress (soluble ST2, interleukin-33, α-klotho, growth differentiation factor 15), and platelet activation (thromboxane B₂, soluble P-selectin) were quantified. Unadjusted and multivariable analyses were performed adjusting for age, sex, body mass index, diabetes, smoking, and glomerular filtration rate. Exploratory subgroup analyses assessed treatment-by-subgroup interactions. Correlations were evaluated using Spearman’s rank coefficient. Results In unadjusted analyses, no significant differences were observed between prasugrel and ticagrelor treatment across oxidative and tissue stress biomarkers, or platelet activation in the whole cohort. Exploratory subgroup analyses identified isolated differences, including higher 8-isoprostane levels in ticagrelor vs prasugrel treated smokers (33.52 pg/ml [9.60–514.51] vs 26.39 [9.11–217.63]; p=0.041) and lower NADPH oxidase 2 levels in statin users on ticagrelor compared to prasugrel (2.10 U/ml [1.98–21.14] vs 2.54 [2.00–44.37]; p=0.022). However, no treatment-related differences were observed in the overall cohort or within any subgroup after multivariable adjustment (Table, Figure). In the whole study population, thioredoxin-1 correlated with soluble P-selectin (Spearman ρ=0.59). Conclusions In this randomized study of AMI patients undergoing pPCI, no differences in oxidative stress, tissue/inflammatory stress, or platelet activation were observed between prasugrel- and ticagrelor treatment, suggesting similar biological effects beyond platelet aggregation. The observed association between thioredoxin-1 and soluble P-selectin indicate a link between redox activity and platelet activation in AMI, independent of treatment.