Does clopidogrel resistance or pharmacogenetic mismatch affect 90-day outcomes in patients with acute ischemic stroke?
572 patients with acute ischemic stroke (median age 67 years) who underwent clopidogrel genetic testing
Clopidogrel resistance (CR) based on CYP2C19 metabolic phenotypes and pharmacogenetic mismatch
Clopidogrel-sensitive (CS) and pharmacogenetically matched patients
Poor neurological outcomes and composite adverse events at 90 dayscomposite
In a real-world registry of acute ischemic stroke patients, CYP2C19-defined clopidogrel resistance was common but not independently associated with poor 90-day clinical outcomes.
Abstract Background and aims Clopidogrel resistance (CR), largely influenced by CYP2C19 polymorphisms, may affect clinical outcomes in acute ischemic stroke (AIS). This study aimed to determine the prevalence of CR, describe CYP2C19 genotype distribution, and evaluate the association between clopidogrel-related genetic variants, CR, and clinical prognosis in AIS patients. Methods AIS patients admitted to the Second Affiliated Hospital of Soochow University between January 2019 and November 2024 who underwent clopidogrel genetic testing were consecutively enrolled. Patients were classified as clopidogrel-sensitive (CS) or CR according to CYP2C19 metabolic phenotypes. Those receiving clopidogrel for secondary prevention were further divided into pharmacogenetically matched or mismatched groups. Baseline characteristics, laboratory and imaging findings, and 90-day outcomes were compared, and logistic regression was performed to identify predictors of poor neurological outcomes and composite adverse events. Results A total of 572 AIS patients (median age 67 years) were included, of whom 61.4% were classified as CR. Intermediate and poor metabolizers predominated. CR patients showed higher rates of hyperuricemia and renal insufficiency. Pharmacogenetically mismatched patients accounted for 10.7% and differed from matched patients in several clinical and laboratory characteristics. Multivariate analysis identified age, diabetes, hyperuricemia, prior stroke, baseline NIHSS score, leukocyte count, and homocysteine as independent predictors of poor 90-day outcomes, whereas CR and pharmacogenetic mismatch were not associated with prognosis or composite adverse events. Conclusions CR was common in AIS patients, mainly driven by CYP2C19*1/*2 and *2/*2 genotypes, but neither CR nor pharmacogenetic mismatch was independently associated with unfavorable outcomes. Conflict of interest All authors claim that they have no conflict of interests to disclose.
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Cao et al. (Fri,) studied this question.
www.synapsesocial.com/papers/69fd7fa1bfa21ec5bbf08342 — DOI: https://doi.org/10.1093/esj/aakag023.254
Yongjun Cao
Rongguang Ge
Shoujiang You
European Stroke Journal
Soochow University
Second Affiliated Hospital of Soochow University
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