ABSTRACT NUMBER: ESOC2026A2297 USEFULNESS OF PHARMACOGENETIC DATA FOR PREDICTING VASCULAR OUTCOMES AND PHARMACODYNAMIC EFFICACY IN CLOPIDOGREL-TREATED ISCHEMIC STROKE PATIENTS

Abstract Background and aims Clopidogrel is a prodrug activated mainly by the polymorphic CYP2C19 enzyme. Because clopidogrel resistance is common and clinical recommendations for pharmacogenetic testing remain uncertain, we examined pharmacogenetic profiles of patients treated with clopidogrel and their associations with platelet function and subsequent thromboses or bleedings. Methods Patients who started clopidogrel during a hospital admission were identified from Turku University Hospital data pool. Genomic data from the FinnGen project were linked with demographic and clinical information. A subset—mostly acute ischemic stroke patients—had platelet function testing using the MPADP assay (Roche). Clinically relevant outcomes were captured as emergency procedures for acute bleedings or thromboses (including thrombectomies and thrombolysis) occurring 7–365 days after clopidogrel initiation. Pharmacogenetic results did not guide treatment. Patients were grouped by CYP2C19 phenotype and by MPADP response category (increased/normal/decreased) using manufacturer cut-offs. Analyses used chi-square testing and correlation methods (Kendall’s tau-b, Spearman’s rho) as appropriate. Results Among 62,015 patients with genomic data, 3,751 received clopidogrel with complete follow-up. There were 112 acute thromboses (3%) and 27 acute bleedings (0.7%), with no significant associations between CYP2C19 phenotype and either outcome. Platelet function results were available for 433 patients. Platelet response showed a weak, non-significant trend toward better response with higher CYP2C19 metabolic phenotypes. Non-response remained high: more than one-third of rapid and ultrarapid metabolizers were non-responders (Figure). Conclusions In this cohort, CYP2C19 phenotype was not significantly associated with thromboses, bleedings, or platelet function. Randomized trials of pharmacogenetically guided selection of clopidogrel versus alternative antiplatelets are needed. Conflict of interest Jori Ruuskanen: Scientific consultancy fees (AstraZeneca, Amgen), travel expenses reimbursement (UCB Pharma), employed and equity interest (Medbase, Turku, Finland). Juuso Blomster: Employed and equity interest in Precordior Oy, honoraria from Novo Nordisk and Roche Diagnostics. Pauli Ylikotila: Speaker fee (AstraZeneca). Niina Kannisto, Lila Kallio, Päivi Helmiö, Aleksi Tornio, Johanna Schleutker: Nothing to disclose. Figure 1 - belongs to Conclusions