Clopidogrel resistance is driven by multifactorial mechanisms including genetic factors like CYP2C19 polymorphisms, epigenetic regulators, drug-drug interactions, and clinical comorbidities.
Abstract Background and aims Clopidogrel is a key antiplatelet agent for preventing thrombotic cardiovascular events. However, clopidogrel resistance limits its therapeutic efficacy and increases the risk of adverse cerebrocardiovascular outcomes. Understanding the mechanisms underlying this resistance is essential for optimizing treatment and improving patient outcomes. Methods This review summarizes current knowledge on the multifactorial mechanisms of clopidogrel resistance. Genetic factors, such as CYP2C19 polymorphisms, significantly influence drug metabolism, while epigenetic regulators including circRNAs and miRNAs modulate gene expression. In addition, drug–drug interactions and clinical conditions—particularly comorbidities and inflammatory states—can also affect antiplatelet response and treatment efficacy. Results Clarifying the interplay among genetic, epigenetic, and pharmacological factors and identifying novel biomarkers are current research priorities. In the future, the integration of genetic testing and platelet function assessment may help achieve precision therapy and guide the development of new antiplatelet or adjunctive strategies to reduce clopidogrel resistance and improve cardiovascular outcomes. Conflict of interest huangxinyi:nothing to disclose
Xinyi Huang (Fri,) conducted a review in Clopidogrel resistance. Clopidogrel was evaluated. Clopidogrel resistance is driven by multifactorial mechanisms including genetic factors like CYP2C19 polymorphisms, epigenetic regulators, drug-drug interactions, and clinical comorbidities.