article · European Stroke Journal
Abstract Background and aims Clopidogrel resistance is prevalent in patients with ischemic stroke or transient ischemic attack (TIA), leading to recurrent cerebrovascular events. However, reported associations for its risk factors are inconsistent. This systematic review and meta-analysis quantifys the sociodemographic, clinical, and genetic predictors of clopidogrel resistance in patients with ischemic stroke or TIA. Methods Following PRISMA guidelines (PROSPERO: CRD420251113725), we systematically searched PubMed, Embase, Scopus, and Web of Science from inception to June 2025. Eligible studies included adults (≥18 years) with ischemic stroke or TIA reporting extractable data for clopidogrel-resistant and non-resistant groups. Results Sixty-five articles (11,786 patients) were included in this systematic review, of which 34 studies (6,053 patients) were included in the analysis. Compared with non-resistant patients, those with clopidogrel resistance were slightly older (MD 1.92 years; 95% CI 1.15–2.68) and had higher HbA1c (MD 0.27%; 95% CI 0.07–0.46), fasting blood glucose (MD 0.62 mmol/L; 95% CI 0.24–0.99), and total cholesterol (MD 0.09 mmol/L; 95% CI 0.004–0.18), but lower hemoglobin levels (MD −0.54 g/dL; 95% CI −1.04 to −0.04). While diabetes mellitus was associated with higher odds of resistance (OR 1.55; 95% CI 1.22–1.97), male sex (OR 0.75; 95% CI 0.65–0.86), current smoking (OR 0.74; 95% CI 0.56–0.97), and the CYP2C19 2 GG genotype (OR 0.45; 95% CI 0.26–0.78) were associated with lower odds of resistance. Conclusions Clopidogrel resistance in stroke/TIA patients is multifactorial, driven by a specific profile of demographic ( age, sex, smoking), metabolic (diabetes, glycemic control) and genetic (CYP2C19) factors. Conflict of interest Yusof M. Omar: Nothing to disclose, Abdullah Almarfadi: Nothing to disclose, Fawaz K Alfahmi: Nothing to disclose, Omar Hammam Salloum : Nothing to disclose, Jamal Ahmad: Nothing to disclose, Abdelrahman Abdelhameed Hashem: Nothing to disclose, Moamen Samy Syaj: Nothing to disclose, Omnia Samy El-Sayed : Nothing to disclose.
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DOI: 10.1093/esj/aakag023.938
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