Key result
The presence of the CYP3A4*1B allele was an independent determinant of poor response to clopidogrel in patients with acute coronary syndrome (OR 4.03; 95% CI 1.01-16.34).
Why the study?
Does genotyping of six clopidogrel-metabolizing enzyme polymorphisms improve the prediction of poor response to clopidogrel in patients with ACS compared to clinical variables alone?
Cross-Sectional (n=278)
Does genotyping of six clopidogrel-metabolizing enzyme polymorphisms improve the prediction of poor response to clopidogrel in patients with ACS compared to clinical variables alone?
Genotyping for six clopidogrel-metabolizing enzyme polymorphisms adds little value to clinical variables in predicting platelet reactivity in ACS patients.
Answers are grounded in this paper and cite their sources.
Genotyping these polymorphisms adds little to platelet reactivity assessment in ACS; leaves open whether targeted testing improves outcomes.
OBJECTIVE: To evaluate the contribution of six polymorphisms to the platelet reactivity in patients with acute coronary syndrome (ACS) treated with clopidogrel. METHODS: Cross-sectional study of 278 consecutive patients with ACS. Detailed clinical information for each patient was collected and genotypes (CYP2C9*2, CYP2C9*3, CYP2C19*2, CYP2C19*17, CYP3A4*1B, and PON1-Q192R) were evaluated with TaqMan® and KASPar® assays. Platelet reactivity was measured with VerifyNow®. RESULTS: Mean age of patients was 66±11 years and 182 (65.5%) patients presented ACS without ST-segment elevation. A total of 206 (74.1%) patients presented poor response to clopidogrel (PRC). CYP2C19*2 polymorphism (p=0.038) was associated with PRC in the univariate setting. In the multiple logistic regression analysis, the risk factors for PRC were the presence of CYP3A4*1B allele (odds ratio [OR] 4.03; 95% confidence interval [CI] 1.01-16.34), age (OR 1.43; 95% CI 1.03-2.00), and body mass index (OR 4.05; 95% CI 1.21-13.43), whereas elevated hemoglobin was a protective factor. Discrimination of PRC through the model that included the six polymorphisms added modest information to the model based on clinical variables (C statistic difference 3.9%). CONCLUSION: CYP3A4*1B allele may be an independent determinant of PRC in patients with ACS, although the variability in response to clopidogrel explained by the six polymorphisms is poor when compared to clinical variables.
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María Henar García-Lagunar (2017) conducted a cross-sectional in acute coronary syndrome (n=278). CYP3A4*1B allele was evaluated on poor response to clopidogrel (PRC) (OR 4.03, 95% CI 1.01-16.34). The presence of the CYP3A4*1B allele was an independent determinant of poor response to clopidogrel in patients with acute coronary syndrome (OR 4.03; 95% CI 1.01-16.34).
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