Key result
CYP2C19 loss-of-function alleles linked to ~2.3-fold higher risk of recurrent stroke or TIA.
Why the study?
CYP2C19 polymorphisms influence clopidogrel metabolism, which may affect long-term prognosis after acute ischemic stroke due to large-artery atherosclerosis.
Does CYP2C19 poor or intermediate metabolizer status increase the long-term risk of recurrent ischemic events in patients with large-artery atherosclerosis stroke?
Cohort (n=369)
Yes
Does CYP2C19 poor or intermediate metabolizer status increase the long-term risk of recurrent ischemic events in patients with large-artery atherosclerosis stroke?
Hazard Ratio: 2.33 (95% CI 1.28–4.24)
Absolute Event Rate: 20.1% vs 9.3%
p-value: p=<0.01
CYP2C19 loss-of-function alleles are strongly associated with a more than doubled long-term risk of recurrent ischemic events in LAA stroke patients, highlighting the potential value of genotype-guided antiplatelet therapy.
CYP2C19 PM/IM status was associated with more than doubled recurrent stroke risk; leaves open whether genotype-guided therapy reduces events in LAA stroke.
BACKGROUND: CYP2C19 polymorphisms influence clopidogrel metabolism, which may influence long-term stroke prognosis. OBJECTIVES: The authors sought to investigate whether CYP2C19 polymorphisms were associated with long-term recurrent ischemic events in patients with acute ischemic stroke due to large-artery atherosclerosis (LAA). METHODS: The present study, comprising a sub-data set from the National Cerebral and Cardiovascular Center Genome Registry-a data registry from a multicenter, prospective, observational study-enrolled patients with LAA stroke within 7 days of stroke onset who consented to genotyping of CYP2C19 polymorphism between 2004 and 2022. Based on CYP2C19 polymorphisms, participants were assigned to 1 of 3 groups: extensive metabolizers (∗1/∗1), intermediate metabolizers (∗1/∗2, ∗1/∗3), and poor metabolizers (∗2/∗2, ∗2/∗3, ∗3/∗3). The primary endpoint was the recurrence of symptomatic ischemic stroke/transient ischemic attack. RESULTS: Among 369 participants with LAA stroke (96 females [26.0%]; age, median [Q1-Q3], 74 [65-80] years) and a median follow-up of 5.1 years, poor or intermediate metabolizers (PM/IMs) (n = 164) had a significantly higher risk of recurrent symptomatic ischemic stroke transient ischemic attack than extensive metabolizers (n = 205) (adjusted HR: 2.33; 95% CI: 1.28-4.24). Furthermore, restricting the analysis to patients taking clopidogrel, PM/IMs exhibited a similarly significant risk (adjusted HR: 5.26; 95% CI: 1.87-14.56). CONCLUSIONS: In patients with LAA stroke, CYP2C19 PM/IMs had a significantly higher long-term recurrence rate of ischemic events than extensive metabolizers.
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Yoshimoto et al. (2025) conducted a cohort in Acute ischemic stroke due to large-artery atherosclerosis (LAA) (n=369). CYP2C19 poor or intermediate metabolizers (PM/IMs) vs. CYP2C19 extensive metabolizers was evaluated on Recurrence of symptomatic ischemic stroke/transient ischemic attack (TIA) (HR 2.33, 95% CI 1.28-4.24, p=<0.01). In patients with large-artery atherosclerotic stroke, being a CYP2C19 poor or intermediate metabolizer significantly increased the risk of recurrent symptomatic ischemic stroke or TIA compared to extensive metabolizers (HR 2.33).
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