Key result
The P2RY1:A236G genetic variant was associated with significantly reduced platelet inhibition by clopidogrel in cats with hypertrophic cardiomyopathy.
Why the study?
Clopidogrel is frequently used in cats with HCM to prevent thromboembolism, but significant interpatient variability in response has been suspected.
Does genetic polymorphism in P2RY1, P2RY12, and CYP2C41 alter platelet inhibition by clopidogrel in cats with hypertrophic cardiomyopathy?
Observational (n=49)
Does genetic polymorphism in P2RY1, P2RY12, and CYP2C41 alter platelet inhibition by clopidogrel in cats with hypertrophic cardiomyopathy?
p-value: p=0.012
A genetic polymorphism in the P2RY1 gene (A236G variant) significantly reduces platelet inhibition by clopidogrel in cats with hypertrophic cardiomyopathy, providing a mechanism for clopidogrel resistance.
P2RY1 variant may blunt clopidogrel response in feline HCM; hypothesis-generating and should not yet alter practice.
Clopidogrel is converted to its active metabolite by cytochrome P450 isoenzymes and irreversibly inhibits platelet activation by antagonizing the adenosine-diphosphate (ADP) receptor. It is frequently used in cats with hypertrophic cardiomyopathy (HCM) to prevent thromboembolic complications. However, significant interpatient variability of the response to clopidogrel therapy has been suspected. In this study, we assessed the impact of single nucleotide polymorphisms (SNPs) within ADP receptor (P2RY1, P2RY12) and cytochrome P450 isoenzyme (CYP2C41) genes on platelet inhibition by clopidogrel administration in cats with HCM. Forty-nine cats completed the study, and blood samples were obtained before and after clopidogrel therapy to assess the degree of platelet inhibition based on flow cytometry and whole blood platelet aggregometry. Plasma concentrations of clopidogrel metabolites were measured after the last dose of clopidogrel. Whole blood platelet aggregometry revealed a significant reduction of platelet inhibition by clopidogrel in cats with the P2RY1:A236G and the P2RY12:V34I variants. The association with the P2RY1:A236G variant and clopidogrel resistance remained significant after adjustment for multiple comparisons. This study demonstrated that a genetic polymorphism in the P2RY1 gene altered response to clopidogrel therapy and suggests that clinicians may consider alternative or additional thromboprophylactic therapy in cats with the P2RY1:A236G variant.
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Ueda et al. (2021) conducted an observational in Hypertrophic cardiomyopathy (n=49). P2RY1:A236G variant vs. P2RY1:A236G wildtype was evaluated on Percent inhibition of area under the curve (AUC) for platelet aggregation (p=0.012). The P2RY1:A236G genetic variant was associated with significantly reduced platelet inhibition by clopidogrel in cats with hypertrophic cardiomyopathy.
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