title: The role of the cytochrome P450 polymorphisms in clopidogrel efficacy and clinical utility.
abstract: Clopidogrel, an antiplatelet agent, prevents platelet aggregation by inhibiting the adenosine disphosphate (ADP) P2Y12 receptor, which is located on the platelet surface. Although dual antiplatelet therapy appears to be efficient, a considerable number of patients continue to experience adverse cardiovascular events, such as stent thrombosis. The percentage of low response to antiplatelet therapy varies from 4% to 30% of patients depending on the cut-off values. In addition, several factors such as poor absorption, drug-to-drug interactions, inadequate dosing, elevated body mass index, insulin resistance and the nature of acute coronary syndromes have been implicated in low clopidogrel response. Recently, studies have focused on the role of genetic polymorphisms encoding enzymes that participate in clopidogrel hepatic metabolism or receptors involved in intestinal absorption and ADP induced platelet aggregation, which may affect the percentage of platelet inhibition after clopidogrel administration. The management of clopidogrel resistance remains a controversial issue and additional studies are required to evaluate the safety and efficacy of increased loading of clopidogrel or replacement with other new antiplatelet agents such as prasugrel.
authors.affiliation: 1st Cardiology Unit, Athens University Medical School, Hippokration Hospital, Vasilissis Sofias 114, 115 28, Athens, Greece. drtousoulis@hotmail.com
authors.forename: D
authors.initials: D
authors.lastname: Tousoulis
authors.forename: G
authors.initials: G
authors.lastname: Siasos
authors.forename: M
authors.initials: M
authors.lastname: Zaromytidou
authors.forename: N
authors.initials: N
authors.lastname: Papageorgiou
authors.forename: E
authors.initials: E
authors.lastname: Stefanadi
authors.forename: E
authors.initials: E
authors.lastname: Oikonomou
authors.forename: C
authors.initials: C
authors.lastname: Stefanadis
mesh_terms: D002986:Clinical Trials as Topic; D000077144:Clopidogrel; D003577:Cytochrome P-450 Enzyme System / Q000235:genetics* / Q000378:metabolism / Q000502:physiology; D006801:Humans; D017202:Myocardial Ischemia / Q000188:drug therapy; D010975:Platelet Aggregation Inhibitors / Q000737:chemistry* / Q000627:therapeutic use; D011110:Polymorphism, Genetic; D013988:Ticlopidine / Q000031:analogs & derivatives* / Q000737:chemistry / Q000627:therapeutic use
chemical_list: D010975:Platelet Aggregation Inhibitors; D003577:Cytochrome P-450 Enzyme System; D000077144:Clopidogrel; D013988:Ticlopidine