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Patients with large-artery atherosclerotic stroke who are poor or intermediate CYP2C19 metabolizers have over twice the long-term recurrence risk of ischemic events compared with extensive metabolizers, especially when treated with clopidogrel.
Genotype-driven antiplatelet response remains a major focus in stroke precision medicine, as CYP2C19 polymorphisms directly influence clopidogrel metabolism and clinical effectiveness. Emerging evidence indicates that variations in this enzyme may shape long-term cerebrovascular outcomes, particularly in patients with large-artery atherosclerosis (LAA) stroke who rely on antiplatelet therapy for secondary prevention.
The investigators aimed to determine whether CYP2C19 polymorphisms were linked with long-term recurrent ischemic events in people presenting with acute LAA stroke. The study analyzed a sub-dataset from the National Cerebral and Cardiovascular Center (NCVC) Genome Registry, which functioned as part of a multicenter, prospective, observational cohort. Eligible participants included individuals who presented with LAA stroke within 7 days of symptom onset and provided consent for CYP2C19 genotyping between 2004 and 2022. Participants were categorized into three metabolizer groups based on CYP2C19 genotypes:
The primary endpoint focused on the recurrence of symptomatic ischemic stroke or transient ischemic attack (TIA). Statistical analyses evaluated long-term outcomes and adjusted for key clinical covariates. The analysis included 369 patients with LAA stroke (median age 74 years; 26% female) and followed them for a median duration of 5.1 years. The findings were as follows:
The investigation demonstrated that CYP2C19 loss-of-function variants were associated with markedly higher long-term ischemic recurrence among patients with LAA stroke, particularly in those treated with clopidogrel. These findings reinforced the relevance of genotype-guided antiplatelet selection and highlighted the increasing role of pharmacogenomics in optimizing secondary stroke prevention strategies.
Journals of the American College of Cardiology
CYP2C19 Polymorphism and Clopidogrel Efficacy in Long-Term Outcomes of Large-Artery Atherosclerotic Stroke: The NCVC Genome Registry
Takeshi Yoshimoto et al.
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