title: Genetics of platelet inhibitor treatment.
abstract: Dual antiplatelet therapy with aspirin and a P2Y12 receptor antagonist is the standard of care in patients undergoing percutaneous coronary intervention (PCI) and in patients with acute coronary syndromes (ACS) because this regimen has markedly decreased the rate of cardiovascular events. The substantial variability in pharmacodynamic response as well as the moderate antiplatelet efficacy of clopidogrel has raised major concerns, since high on-clopidogrel platelet reactivity has consistently been associated with increased risk for ischaemic events in PCI patients. Baseline demographic and clinical variables contributing to the observed variability have been identified. Besides this, research within the past decade has focused on the impact of genetic polymorphisms encoding transport systems or enzymes involved in the absorption and metabolism of these drugs. Loss-of-function polymorphisms in CYP2C19 are the strongest individual variables affecting pharmacokinetics and antiplatelet response to clopidogrel, but explain no more than 5 to 12% of the variability in adenosine diphosphate-induced platelet aggregation on clopidogrel. No genetic variables contributing to clinical outcomes of patients treated with the newer P2Y12 receptor antagonists, prasugrel or ticagrelor, have been identified so far. This review aims to provide an update on the current status of genotype-based personalized therapy with clopidogrel.
authors: Klinik für Kardiologie und Angiologie II, Universitäts-Herzzentrum Freiburg-Bad Krozingen, Bad Krozingen, Germany.
authors: Dietmar
authors: D
authors: Trenk
authors: Willibald
authors: W
authors: Hochholzer
mesh_terms: D018435:ATP Binding Cassette Transporter, Subfamily B / Q000235:genetics; D043303:Aryldialkylphosphatase / Q000235:genetics*; D002265:Carboxylic Ester Hydrolases / Q000235:genetics*; D000077144:Clopidogrel; D065731:Cytochrome P-450 CYP2C19 / Q000235:genetics*; D060005:Genotyping Techniques; D006801:Humans; D008969:Molecular Sequence Data; D010597:Pharmacogenetics; D010975:Platelet Aggregation Inhibitors / Q000009:adverse effects / Q000493:pharmacokinetics* / Q000627:therapeutic use; D011110:Polymorphism, Genetic / Q000235:genetics; D057285:Precision Medicine; D058921:Purinergic P2Y Receptor Antagonists / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use; D013988:Ticlopidine / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000493:pharmacokinetics / Q000627:therapeutic use
chemical_list: C513055:ABCB1 protein, human; D018435:ATP Binding Cassette Transporter, Subfamily B; D010975:Platelet Aggregation Inhibitors; D058921:Purinergic P2Y Receptor Antagonists; D000077144:Clopidogrel; C045793:CYP2C19 protein, human; D065731:Cytochrome P-450 CYP2C19; D002265:Carboxylic Ester Hydrolases; C474609:CES1 protein, human; D043303:Aryldialkylphosphatase; C468406:PON1 protein, human; D013988:Ticlopidine
keywords: P2Y12 antagonist; clopidogrel; platelet inhibitor; prasugrel; single nucleotide polymorphism; ticagrelor
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