Association of Clopidogrel Genetic Polymorphism With Efficacy and Safety for Ischemic Stroke or Transient Ischemic Attack: A Systematic Review and Updated Meta-Analysis

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 in-cluded 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 fol-lowing 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.