CYP2C19 Genotype and Stroke Risk Score: Implications for Clopidogrel Therapy and Recurrent Events

Clopidogrel, a commonly used antiplatelet agent for stroke prevention, requires CYP2C19-mediated metabolism for efficacy. Loss-of-function alleles reduce clopidogrel’s antiplatelet effect, potentially leading to treatment failure. This study aimed to determine the prevalence of CYP2C19 polymorphisms in a Thai population and the association of these polymorphisms with recurrent cardiovascular events.

This retrospective chart review included patients who presented to Bangkok Hospital, Thailand (January 2014–December 2023), for whom CYP2C19 genetic testing results were available. Patients were categorized as carriers or noncarriers of loss-of-function alleles. The Essen Stroke Risk Score (ESRS) was used to stratify patients at high risk (≥3) or low risk (<3) for recurrent stroke. The primary outcome was either recurrent ischemic stroke or myocardial infarction. Log-rank test was used to assess differences in event rates between groups.

Among the 126 patients (mean age 70.45 ± 12.48 years, 74.6% male), the CYP2C19 phenotypes were distributed as follows: normal metabolizers (31%), intermediate metabolizers (48.4%), poor metabolizers (12.7%), and ultrarapid metabolizers (7.9%). All recurrent cardiovascular events occurred in the carriers. Compared to noncarriers, carriers exhibited significantly greater rates of recurrent stroke (p=0.028) and recurrent myocardial infarction (p=0.04). Recurrent stroke and myocardial infarction were significantly more frequent in carriers only within the high ESRS group.

Loss-of-function CYP2C19 alleles were prevalent in more than half of the studied population. Carriers demonstrated a significantly increased risk for recurrent cardiovascular events. Pretreatment CYP2C19 genotyping should be considered to prevent adverse outcomes in clopidogrel-treated patients, particularly those with high ESRS (≥3).