CYP2C19 Genetic Variability, ADP-Induced Whole-Blood Platelet Aggregation, and Clopidogrel Response in an Exploratory Retrospective Cohort of Acute Ischemic Stroke

BackgroundPatient response to clopidogrel varies due to CYP2C19 genetic polymorphisms. Impaired metabolism has been linked to an increased risk of recurrent ischemic events. The purpose of this study was to examine CYP2C19 phenotypes and the impact on ADP aggregation in whole blood platelet aggregometry (WBPA) in patients with acute ischemic stroke (AIS).MethodsPatients with AIS or transient ischemic attack (TIA) from two academic comprehensive stroke centers between January 2022 and May 2025 were retrospectively reviewed. Inclusion criteria required both CYP2C19 genotyping and WBPA. Categorical variables were compared using chi-square test and continuous variables using Mann-Whitney U test. Multivariable logistic regression identified independent predictors of inadequate platelet inhibition defined by ADP aggregation threshold.ResultsAmong 112 patients (metabolizers: N=62, non-metabolizers: N=50), there was no correlation between CYP2C19 metabolizer phenotype and ADP-induced platelet aggregation (p=0.49). The study found substantial racial (p=0.012) and Hispanic ethnic (p=0.001) differences in metabolizer phenotype. Inadequate platelet inhibition was also associated with age (p=0.020) loading phase (p=0.04), underscoring the need to consider demographic variables, patient characteristics, and the timing of platelet function testing when interpreting platelet reactivity results and making clinical decisions.ConclusionThis study found no significant association between an individual's CYP2C19 metabolizer status and ADP-induced platelet aggregation. The results of this study may help advance understanding of pharmacogenomics, but care must be taken when interpreting them due to this study's limitations. These findings should be confirmed in a future study.