Key result
CYP2C19*2 allele linked to higher platelet aggregation during clopidogrel therapy before and after PCI.
Why the study?
The concentration of clopidogrel's inactive carboxylic acid metabolite may help evaluate therapy response, prompting evaluation of its correlation with platelet aggregation inhibition and genetic polymorphisms in PCI patients.
Do genetic polymorphisms (CYP2C19, CYP3A4/5, ABCB1, PON1) affect clopidogrel inactive metabolite levels and antiplatelet response in patients after percutaneous coronary intervention?
Observational (n=155)
No
Do genetic polymorphisms (CYP2C19, CYP3A4/5, ABCB1, PON1) affect clopidogrel inactive metabolite levels and antiplatelet response in patients after percutaneous coronary intervention?
Absolute Event Rate: 415.87% vs 262.6%
p-value: p=0.0006
The CYP2C19*2 allele is associated with decreased platelet reactivity during clopidogrel therapy, and simultaneous determination of platelet aggregation and inactive metabolite concentration may help identify causes of insufficient treatment effect.
CYP2C19*2 was associated with higher on-treatment platelet reactivity post-PCI; supports genotyping for response prediction but leaves metabolite monitoring utility open.
BACKGROUND AND OBJECTIVE: Clopidogrel is frequently used as part of optimal dual antiplatelet therapy in high-bleeding risk patients with the acute coronary syndrome. The concentration of the inactive carboxylic acid metabolite of clopidogrel might be useful to evaluate the response to clopidogrel therapy. Therefore, we sought to correlate the inhibition of platelet aggregation with the plasma level of the inactive metabolite of clopidogrel in patients after percutaneous coronary interventions (PCI) and their associations with the most frequently studied genetic polymorphisms. For this purpose, the fast and simple HPLC method for determining the concentration of the inactive metabolite was developed. METHODS: The effect of CYP2C19, CYP3A4/5, ABCB1 and PON1 genes on the plasma inactive metabolite concentration of clopidogrel and the platelet aggregation was investigated in 155 patients before and after PCI. RESULTS: The concentration of the inactive metabolite of clopidogrel was not significantly different in the intermediate metabolizers (IM) of CYP2C19 compared with extensive metabolizers (EM) both before and after PCI, while inhibition of platelet aggregation was found to be significantly better in EM than in IM. The presence of the A allele at position 2677 in the ABCB1 gene was associated with a significantly lower concentration of inactive metabolite of clopidogrel before PCI. CONCLUSION: The CYP2C19*2 allele was associated with decreased platelet reactivity during clopidogrel therapy before and after PCI. Simultaneous determination of platelet aggregation and concentration of the inactive clopidogrel metabolite may be useful in clinical practice to find the cause of adverse effects or insufficient treatment effect in patients chronically treated with clopidogrel.
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Adamiak-Giera et al. (2020) conducted an observational in Coronary artery disease requiring percutaneous coronary intervention (n=155). CYP2C19*2 allele (Intermediate Metabolizers) vs. CYP2C19 Extensive Metabolizers was evaluated on Platelet aggregation (AUC agr in AU·min) after PCI (p=0.0006). The presence of the CYP2C19*2 allele was associated with significantly decreased platelet inhibition (higher platelet aggregation) during clopidogrel therapy both before and after percutaneous coronary intervention.
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