Farmacogenética e a resposta ao tratamento do Clopidogrel em pacientes do HC-UFTM

Abstract

Variability in response to clopidogrel, a widely used prodrug in the treatment of cardiovascular diseases, is modulated by clinical and genetic factors, with particular emphasis on variants in the CYP2C19 gene, which encodes the enzyme responsible for converting clopidogrel into its active metabolite. This study aimed to evaluate the influence of genetic variants of the CYP2C19 gene on clopidogrel response, as well as to investigate the clinical applicability of genotyping and point-of-care platelet function testing in hospital practice. It involved a prospective cohort of 289 patients undergoing Percutaneous Coronary Intervention (PCI) at the Hospital de Clínicas of the Federal University of Triângulo Mineiro (HC-UFTM). The CYP2C19 *2, *3, and *17 variants, associated with loss or gain of enzymatic function, were analyzed, along with platelet aggregation using the VerifyNow P2Y12® assay. The observed allele frequencies were 0.13 for *2, 0.1 for *3, and 0.18 for *17. Platelet function analysis revealed that individuals carrying at least one loss-of-function allele exhibited higher platelet reactivity compared to individuals without a loss-of-function allele (p=0.011), suggesting reduced therapeutic effectiveness in these subjects. Moreover, intermediate metabolizers with the *2/*17 genotype showed significantly higher platelet reactivity than ultrarapid metabolizers (*17/*17) (p=0.0086) and normal metabolizers (*1/*1) (p=0.015). These findings underscore the importance of integrating pharmacogenetics with platelet function testing to personalize antiplatelet therapy, although the implementation of this approach in Brazilian clinical practice still faces structural and economic challenges.