Challenges and prospects of CYP2C19 genotype-guided clopidogrel therapy from the perspective of precision medicine

In the era of precision medicine, dual antiplatelet therapy with aspirin and a P2Y12 receptor inhibitor is the standard strategy for patients after percutaneous coronary intervention (PCI). Clopidogrel, as a widely used representative drug, has its efficacy significantly influenced by CYP2C19 genetic polymorphisms, leading to poor metabolism in some patients, insufficient exposure to active metabolites, and increased risk of ischemic events. In theory, CYP2C19 genotyping to guide individualized antiplatelet therapy could help optimize the clinical selection of P2Y12 inhibitors and improve prognosis. However, current evidence and guidelines do not support its use as a routine test for post-PCI patients, reflecting multiple challenges in clinical translation. From the perspective of precision medicine, this article systematically reviews the main problems and clinical application dilemmas of CYP2C19 genotyping in guiding clopidogrel therapy, including controversies and uncertainties in randomized controlled trials (RCTs) evidence, neglect of rare alleles, complexity of metabolism regulated by polygenic and clinical factors, and limited predictive value for low platelet reactivity. Finally, this paper prospects future research directions and clinical translation prospects, aiming to provide a theoretical reference for promoting individualized antiplatelet therapy and balancing thrombosis and bleeding risks.