Interindividual variability in platelet aggregation among aspirin-treated patients: a large retrospective analysis

Interindividual variability in response to aspirin remains a major challenge in antiplatelet therapy. Identification of patients with high (HPR), optimal (OPR) or low platelet reactivity (LPR) remains challenging and may be influenced by both biological and methodological factors, including interlaboratory variability. We report results of a large cohort of aspirin-treated patients to assess the gold standard light transmission aggregometry (LTA). We retrospectively analyzed 3,065 patients treated with aspirin (ASA; 75-150 mg/day) who sequentially underwent LTA assessment using multiple agonists (ADP 2μM, collagen 2 μg/mL, arachidonic acid [AA] 0.75 mM, epinephrine 10μM). Patients were stratified according to AA-induced platelet aggregation using a 16% cut-off (third quartile). Patients with AA >16% showed significantly higher platelet aggregation across all agonists (p<0.0001). However, a substantial proportion of patients with AA ≤16%, consistent with effective COX-1 inhibition, still exhibited high platelet reactivity when stimulated with ADP, epinephrine or collagen. Collagen-induced aggregation was particularly informative in identifying residual platelet reactivity. Sex-related differences were observed, with females showing higher platelet reactivity, especially to ADP and collagen. Platelet reactivity in aspirin-treated patients is highly heterogeneous, with hyper- or hypo-reactive phenotype potentially affecting the safety and efficacy of antiplatelet therapy. AA-induced aggregation alone is insufficient to fully characterize platelet responsiveness. A multiagonist approach, particularly including collagen, may improve identification of patients with residual platelet reactivity and support personalized antiplatelet strategies. These data support ongoing strategies of guided selection of antiplatelet therapy in patients with cardiovascular disease.