Implementation of clopidogrel pharmacogenetics: a Brazilian perspective

Abstract

The CYP2C19 gene encodes one of the main enzymes responsible for clopidogrel bioactivation, a widely prescribed antiplatelet prodrug. Due to its high polymorphism, clopidogrel response varies considerably, especially in carriers of nonfunctional alleles, such as CYP2C192 and * 3. Meta-analyses have associated CYP2C19 loss-of-function alleles with worse cardiovascular outcomes, and genotype-guided strategies have demonstrated feasibility and clinical utility, supporting the rationale for locally validated implementation in Brazil. Personalized treatment strategies, based on preemptive genotyping and genotype-guided recommendations, have been proposed to improve clopidogrel efficacy and safety. However, extrapolating international guidelines to genetically diverse and underrepresented populations, such as Brazilians, poses challenges. Therefore, to discuss the clinical application of this testing in Brazil, it is also necessary to explore strategies that promote national pharmacogenomic studies, enhance infrastructure and training, and better align public policies. This study followed a contextual synthesis approach, with evidence identified through PubMed (last updated July 2025), and discusses structural and scientific barriers to implementing precision medicine in a local context of Brazil, proposing strategies for CYP2C19-clopidogrel pharmacogenetics at the Hospital de Clínicas of the Universidade Federal do Triângulo Mineiro (HC-UFTM), Minas Gerais, Brazil, considering both local realities and broader systemic limitations.

Keywords: Brazil; CYP2C19; Pharmacogenomics implementation; clopidogrel; genetic diversity; precision medicine.