Genetic determinants of on-clopidogrel high platelet reactivity

Clopidogrel has been used (alone or in association with aspirin) to prevent vascular complications in atherothrombotic patients, to prevent stent thrombosis (ST) in patients undergoing percutaneous coronary intervention (PCI) and as a long-term prevention of cardiovascular and cerebrovascular events. Unfortunately, it is important to note that there are a number of patients who, during clopidogrel therapy, show and maintain a high platelet reactivity (PR), similar to that observed before the start of antiplatelet therapy. Clopidogrel pro-drug is absorbed in the intestine and this process is influenced by P-glycoprotein-1 (P-GP). Its conversion into 2-oxo clopidogrel is regulated by cytochromes (CYP) called CYP2C19, CYP2B6 and CYP1A2. Whereas, the final transformation into the active metabolite is regulated by CYP called CYP2C19, CYP2C9, CYP2B6, CYP3A4, CYP3A5 and, as recently emerged, by the glycoprotein paraoxonase-1 (PON1). The genes encoding these enzymes are characterized by several polymorphisms. Som...