2025-09-16 国立循環器病研究センター
<関連情報>
- https://www.ncvc.go.jp/pr/release/pr_49161/
- https://www.sciencedirect.com/science/article/pii/S2772374725003953
大動脈性動脈硬化性脳卒中の長期転帰におけるCYP2C19多型とクロピドグレル有効性:NCVCゲノムレジストリ CYP2C19 Polymorphism and Clopidogrel Efficacy in Long-Term Outcomes of Large-Artery Atherosclerotic Stroke: The NCVC Genome Registry
Takeshi Yoshimoto MD, PhD, Yorito Hattori MD, PhD, Hiroyuki Ishiyama MD, PhD, Yuriko Nakaoku MD, PhD, Soshiro Ogata PhD, Soichiro Abe MD, Kenji Ninomiya MD, Kunihiro Nishimura MD, PhD, Masafumi Ihara MD, PhD
JACC: Asia Available online: 13 September 2025
DOI:https://doi.org/10.1016/j.jacasi.2025.07.020
Abstract
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.
