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Genetics of platelet inhibitor treatment
Author(s) -
Trenk Dietmar,
Hochholzer Willibald
Publication year - 2014
Publication title -
british journal of clinical pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.216
H-Index - 146
eISSN - 1365-2125
pISSN - 0306-5251
DOI - 10.1111/bcp.12230
Subject(s) - prasugrel , clopidogrel , ticagrelor , p2y12 , cyp2c19 , medicine , percutaneous coronary intervention , aspirin , pharmacodynamics , conventional pci , pharmacology , pharmacogenetics , acute coronary syndrome , platelet aggregation inhibitor , cardiology , pharmacokinetics , genotype , myocardial infarction , biology , cytochrome p450 , metabolism , gene , biochemistry
Dual antiplatelet therapy with aspirin and a P2Y 12 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 P2Y 12 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.