Abstract WP004: CYP2C19 Loss-of-Function Alleles and Early Imaging Outcomes in Clopidogrel-Treated Acute Ischemic Stroke

Introduction: Clopidogrel is widely used for acute ischemic stroke, but its efficacy is influenced by CYP2C19 loss-of-function alleles. Previous studies have shown inconsistent results regarding outcome differences by genotype. We aimed to evaluate imaging and clinical outcomes of clopidogrel-treated stroke patients according to CYP2C19 genotype. Methods: This was a single-center, prospective, registry-based cohort study conducted between January 2022 and June 2024. We included patients aged ≥20 years with acute ischemic stroke within 7 days of onset who received clopidogrel at admission and underwent CYP2C19 genotyping; those treated with endovascular thrombectomy were excluded. Patients carrying *2 or *3 alleles were classified as loss-of-function (LOF) carriers, and all others as non-carriers. The primary outcome was new ischemic lesions on day-5 diffusion-weighted imaging (DWI). Secondary outcomes included infarct growth on day-5 DWI, favorable functional outcome at 90 days (mRS 0–2), early neurological deterioration (END), intracranial hemorrhage (ICH), major bleeding, and vascular death. Results: A total of 317 patients were included (mean age 68.5±12.6 years, 66% male; median NIHSS 3 [IQR 1–5]) in this study. Baseline characteristics were comparable between groups except for older age in LOF carriers. On day-5 DWI, new ischemic lesions were observed in 24% of LOF carriers and 17% of non-carriers (p=0.11), while infarct growth was more frequent in LOF carriers (31% vs 18%, p=0.013). At 90 days, favorable functional outcome rates did not differ significantly (78% vs 84%, p=0.20). In multivariable analyses, LOF carrier status was not independently associated with new ischemic lesions (adjusted OR 1.43, 95% CI 0.74–2.84) but was associated with infarct growth (adjusted OR 1.93, 95% CI 1.08–3.53). Other outcomes, including END, ICH, major bleeding, and vascular death, showed no significant differences between groups. Conclusions: In clopidogrel-treated acute ischemic stroke patients, CYP2C19 loss-of-function allele carriage was not significantly associated with new ischemic lesions at day 5 or favorable functional outcome at 90 days. However, carriers showed a higher risk of infarct growth, indicating reduced antiplatelet response may affect stroke evolution. Further research is needed to evaluate genotype-guided antiplatelet therapy.