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Published on: April 1, 2019
Association of Clopidogrel Genetic Polymorphism With Efficacy and Safety for Ischemic Stroke or Transient Ischemic
Hyungjong Park1, Yo Han Jung2,3, Sooyeoun You4
1Department of Neurology, Keimyung University School of Medicine, Daegu, Korea.
Insights
Patients with CYP2C19 loss-of-function alleles taking clopidogrel face a higher risk of recurrent stroke or TIA. This increased risk is particularly notable in Asian populations, underscoring the need for personalized treatment strategies.
Area of Science:
- Pharmacogenomics
- Cardiovascular Medicine
- Neurology
Background:
- CYP2C19 loss-of-function (LoF) alleles are known to impair clopidogrel metabolism.
- Limited data exists on the association between CYP2C19 LoF alleles and recurrent stroke or transient ischemic attack (TIA) risk in patients on clopidogrel.
- Clopidogrel is a commonly prescribed antiplatelet medication for stroke and TIA patients.
Purpose of the Study:
- To conduct an updated meta-analysis evaluating the relationship between CYP2C19 LoF alleles and the risk of stroke or TIA recurrence.
- To assess the impact of CYP2C19 genotype on clopidogrel efficacy and safety outcomes in patients with a history of stroke or TIA.
Main Methods:
- Systematic literature search across PubMed, Scopus, Cochrane CENTRAL, and Embase.
- Inclusion of studies reporting stroke/TIA recurrence, composite vascular events, or bleeding events as outcomes.
- Meta-analysis conducted following PRISMA guidelines (PROSPERO ID: CRD42024564771).
Main Results:
- Carriers of CYP2C19 LoF alleles showed a significantly higher risk of stroke recurrence (RR, 1.89) and composite vascular events (RR, 1.54) compared to non-carriers.
- Increased recurrence risk was observed in both observational studies (RR, 2.20) and RCT post-hoc analyses (RR, 1.44).
- The risk was particularly pronounced in Asian populations (RR, 1.97); bleeding event incidence was similar between groups.
Conclusions:
- Patients carrying CYP2C19 LoF alleles on clopidogrel therapy have an elevated risk of stroke or TIA recurrence.
- The pharmacogenetic impact on recurrence risk is significantly higher in Asian populations.
- Findings suggest potential utility of CYP2C19 genotyping for personalized antiplatelet therapy selection post-stroke/TIA.
Background And Purpose:
Research suggests that CYP2C19 loss-of-function (LoF) alleles impede the metabolism of clopidogrel. However, there is limited research on the relationship between these alleles and the risk of stroke or transient ischemic attack (TIA) recurrence in patients taking clopidogrel. This updated meta-analysis aims to evaluate the relationship between CYP2C19 LoF alleles and the risk of stroke or TIA recurrence among patients receiving clopidogrel.
Methods:
Relevant literature was obtained from searches of PubMed, Scopus, Cochrane Central Register Controlled Trials (CENTRAL), and Embase. The outcome measures of included studies were stroke or TIA, composite vascular events as an efficacy, and bleeding as a safety outcome. This meta-analysis was conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines (PROSPERO ID: CRD42024564771).
Results:
An analysis of 28 studies encompassing 11,401 patients treated with clopidogrel following stroke or TIA revealed that carriers of CYP2C19 LoF alleles had significantly higher risk of stroke recurrence compared to non-carriers (risk ratio [RR], 1.89; 95% confidence interval [CI]: 1.55-2.32). Composite vascular events were also significantly more frequent in carriers of the CYP2C19 LoF allele than in non-carriers (RR, 1.54; 95% CI: 1.16-2.04). Both observational studies (RR, 2.20; 95% CI: 1.74-2.79) and post-hoc analyses of randomized controlled trials (RR, 1.44; 95% CI: 1.04-1.99) demonstrated significantly increased recurrence risk among carriers of these alleles. This risk was especially pronounced in Asian populations (RR, 1.97; 95% CI: 1.60-2.43). There was insufficient data specific to other ethnic groups for definite conclusions. The incidence of bleeding events was similar between groups.
Conclusions:
Carriers of CYP2C19 LoF alleles treated with clopidogrel had a higher risk of stroke or TIA recurrence than non-carriers. This risk was higher in Asian populations.
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