Key result
Carriers of the CES1 143E-allele had significantly greater levels of clopidogrel active metabolite (P=0.001) and better clopidogrel response measured by platelet aggregation.
Why the study?
Does the CES1 G143E variant increase clopidogrel active metabolite levels and improve platelet response in patients treated with clopidogrel?
Observational (n=916)
Does the CES1 G143E variant increase clopidogrel active metabolite levels and improve platelet response in patients treated with clopidogrel?
p-value: p=0.001
The CES1 G143E variant is associated with higher clopidogrel active metabolite levels and greater platelet inhibition, suggesting it is an important genetic determinant of clopidogrel efficacy.
CES1 143E-allele carriage was associated with greater clopidogrel response; extends candidate-gene evidence but leaves clinical utility open.
INTRODUCTION: Carboxylesterase 1 (CES1) is the primary enzyme responsible for converting clopidogrel into biologically inactive carboxylic acid metabolites. METHODS: We genotyped a functional variant in CES1, G143E, in participants of the Pharmacogenomics of Anti-Platelet Intervention (PAPI) study (n=566) and in 350 patients with coronary heart disease treated with clopidogrel, and carried out an association analysis of bioactive metabolite levels, on-clopidogrel ADP-stimulated platelet aggregation, and cardiovascular outcomes. RESULTS: The levels of clopidogrel active metabolite were significantly greater in CES1 143E-allele carriers (P=0.001). Consistent with these findings, individuals who carried the CES1 143E-allele showed a better clopidogrel response as measured by ADP-stimulated platelet aggregation in both participants of the PAPI study (P=0.003) and clopidogrel-treated coronary heart disease patients (P=0.03). No association was found between this single nucleotide polymorphism and baseline measures of platelet aggregation in either cohort. CONCLUSION: Taken together, these findings suggest, for the first time, that genetic variation in CES1 may be an important determinant of the efficacy of clopidogrel.
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Lewis et al. (2012) conducted an observational in Coronary heart disease (n=916). CES1 G143E variant (143E-allele) vs. Non-carriers of the 143E-allele was evaluated on Clopidogrel active metabolite levels and on-clopidogrel ADP-stimulated platelet aggregation (p=0.001). Carriers of the CES1 143E-allele had significantly greater levels of clopidogrel active metabolite (P=0.001) and better clopidogrel response measured by platelet aggregation.
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