CLOPIDOGREL RESISTANCE AND ITS GENETICS

Abstract

Clopidogrel is an antiplatelet drug that is administered in the form of prodrug that
has to be converted to its active metabolite by hepatic cytochrome P450 (CYP)
isoenzymes in the liver. There exists individual response variability of platelets
inhibition by clopidogrel that is an indication that genetic factors are involved in
clopidogrel responsiveness. Combining aspirin and clopidogrel is considered as
gold standard therapy for patients who develop acute coronary syndromes (ACS)
or are undergoing percutaneous coronary intervention (PCI). However, despite
the administration of dual antiplatelet therapy, some patients face recurrent
cardiovascular ischemic events, the most catastrophic is stent thrombosis. It is
well established that the antiplatelet response to clopidogrel varies widely among
patients. Patients who display little attenuation of platelet reactivity under
clopidogrel therapy are recognized as low- or non-responders, or clopidogrelresistant.
Different alleles of cytochrome P450 gene and a number of other genes
are involved in the pharmacokinetics and pharmacodynamics of clopidogrel.
Herein we discussed the mode of action of clopidogrel, mechanism of
clopidogrel resistance and relation of genetic polymorphisms of CYP and other
genes to clopidogrel resistance in patients using clopidogrel.