Key result
CYP2C19*2 carrier status was associated with significantly increased residual platelet aggregation after a 600 mg clopidogrel loading dose compared with noncarriers (OR 4.6; 95% CI 2.5-8.7; P<0.0001).
Why the study?
Does CYP2C19*2 genotype combined with nongenetic risk factors predict high residual platelet aggregation after a 600 mg clopidogrel loading dose in patients undergoing PCI?
Observational (n=237)
Does CYP2C19*2 genotype combined with nongenetic risk factors predict high residual platelet aggregation after a 600 mg clopidogrel loading dose in patients undergoing PCI?
Odds Ratio: 4.6 (95% CI 2.5–8.7)
p-value: p=<0.0001
Combining CYP2C19*2 genotype with clinical risk factors significantly improves the prediction of poor responsiveness to a clopidogrel loading dose in patients undergoing PCI.
Supports adding CYP2C19*2 to clinical models for predicting clopidogrel response in PCI; hypothesis-generating for outcome trials.
AIMS: To investigate an association of responsiveness to clopidogrel loading dose with genotypes of cytochrome P450 (CYP) 2C19, other CYP isozymes and nongenetic factors in patients with coronary artery disease. MATERIALS & METHODS: Genotyping for CYP2C19 (*2, *3 and *17), CYP3A4*1B and CYP3A5*3 variants was performed in patients (n = 237) who underwent percutaneous coronary intervention. Adenosine diphosphate-induced platelet aggregation was determined after first administration of 600 mg clopidogrel. RESULTS: CYP2C19*2 carriers showed significantly increased residual platelet aggregation (RPA) (OR: 4.6; 95% CI: 2.5-8.7; p < 0.0001) compared with noncarriers. All other polymorphisms had no influence on RPA. For the development of a risk score for better prediction of RPA, CYP2C19*2 genotype and previously identified nongenetic risk factors (age >65 years, Type 2 diabetes mellitus, decreased left ventricular function, renal failure and acute coronary syndrome) were analyzed. Multivariable logistic regression analysis showed a significant correlation of the nongenetic factors (chi (2) = 5.32; p = 0.021) and CYP2C19*2 (chi (2) = 21.31; p < 0.0001) with high RPA, and an even higher association for the combination of both (chi (2) = 25.85; p < 0.0001). CONCLUSIONS: Prediction of responsiveness after clopidogrel loading dose may substantially be improved by adding CYP2C19*2 genotype to nongenetic risk factors.
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Geisler et al. (2008) conducted an observational in Coronary artery disease (n=237). CYP2C19*2 carrier status vs. Noncarriers was evaluated on Increased residual platelet aggregation (RPA) (OR 4.6, 95% CI 2.5-8.7, p=<0.0001). CYP2C19*2 carrier status was associated with significantly increased residual platelet aggregation after a 600 mg clopidogrel loading dose compared with noncarriers (OR 4.6; 95% CI 2.5-8.7; P<0.0001).
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