title: Genetic variability in response to clopidogrel therapy and its clinical implications.
abstract: This article concentrates on individual genetic differences responsible for variations of action of clopidogrel, which have been found to be partially responsible for increased cardiovascular events in patients with coronary artery disease under dual antiplatelet therapy. According to these results, genotyping for the relevant gene polymorphisms, especially for the CYP2C19 loss-of-function alleles, has been discussed to be an effective method of individualising and optimising clopidogrel treatment. However, due to the facts that 1) there are no prospective studies demonstrating a clinical benefit of personalising antiplatelet therapy based on genotyping; 2) CYP2C19 polymorphisms account for only approximately 12% of variability in clopidogrel platelet response; 3) the positive predictive value of CYP2C19 loss-of-function polymorphisms for cardiovascular events in patients with acute coronary syndrome undergoing percutaneous coronary intervention is only approximately 12% - 20%; 4) it is likely that other clinical factors and risk constellations might be of greater clinical importance; and 5) it is unknown whether a specific genetic polymorphism is capable of influencing outcome for the individual patient; genetic profiling cannot be recommended for routine use at present but will remain of considerable scientific interest.
authors.affiliation: 3rd Department of Medicine, Cardiology and Emergency Medicine, Wilhelminenhospital, Montleartstrasse 37, Vienna, Austria.
authors.forename: Liana
authors.initials: L
authors.lastname: Yukhanyan
authors.forename: Matthias K
authors.initials: MK
authors.lastname: Freynhofer
authors.forename: Jolanta
authors.initials: J
authors.lastname: Siller-Matula
authors.forename: Karsten
authors.initials: K
authors.lastname: Schrör
authors.forename: Kurt
authors.initials: K
authors.lastname: Huber
mesh_terms: D001189:Aryl Hydrocarbon Hydroxylases / Q000235:genetics*; D000077144:Clopidogrel; D003324:Coronary Artery Disease / Q000188:drug therapy* / Q000235:genetics / Q000503:physiopathology; D065731:Cytochrome P-450 CYP2C19; D004252:DNA Mutational Analysis; D014644:Genetic Variation; D006801:Humans; D010975:Platelet Aggregation Inhibitors / Q000627:therapeutic use*; D011110:Polymorphism, Genetic; D057285:Precision Medicine / Q000639:trends; D011237:Predictive Value of Tests; D013988:Ticlopidine / Q000031:analogs & derivatives* / Q000627:therapeutic use
chemical_list: D010975:Platelet Aggregation Inhibitors; D000077144:Clopidogrel; D001189:Aryl Hydrocarbon Hydroxylases; C045793:CYP2C19 protein, human; D065731:Cytochrome P-450 CYP2C19; D013988:Ticlopidine