title: Advocating cardiovascular precision medicine with P2Y12 receptor inhibitors.
abstract: Antiplatelet therapy with P2Y12-receptor inhibitors has become the cornerstone of medical treatment in patients with acute coronary syndrome treated with percutaneous coronary intervention (PCI). With over 100 million prescriptions filled since its approval, clopidogrel is the most widely used P2Y12-receptor inhibitor. Dual antiplatelet therapy with clopidogrel plus aspirin has been associated with a lower rate of major cardiovascular events in patients after PCI than aspirin monotherapy. However, an alarmingly high number of clopidogrel-treated patients experience adverse thrombotic events. Insufficient P2Y12-inhibition or high on-treatment platelet reactivity to adenosine diphosphate has stimulated the increased use of more potent P2Y12 inhibitors: prasugrel (a third generation thienopyridine) and ticagrelor (a cyclopentyl-triazolo-pyrimidine). However, more potent platelet inhibition and low on-treatment platelet reactivity has resulted in increased major bleeding and higher costs. These limitations have suggested the need for an individualized antiplatelet approach in order to decrease thrombotic events and minimize bleeding. This model of personalized medicine integrates a patient's demographic and biological data (pharmacodynamic, genomic, epigenomic, transcriptomic, and metabolic information) to target therapy in order to maximize efficacy while minimizing bleeding and costs. This review discusses the role of diagnostic tools such as platelet function and pharmacogenomic testing to personalize antiplatelet therapy.
authors.affiliation: Department of Cardiology, Medical University of Vienna, Vienna, Austria.
authors.forename: Max-Paul
authors.initials: MP
authors.lastname: Winter
authors.affiliation: Department of Cardiology, Aarhus University Hospital, Aarhus, Denmark.|Faculty of Health, Institute of Clinical Medicine, Aarhus University, Aarhus, Denmark.
authors.forename: Erik L
authors.initials: EL
authors.lastname: Grove
authors.affiliation: Institute of Cardiology, "G. d'Annunzio" University, Chieti, Italy.
authors.forename: Raffaele
authors.initials: R
authors.lastname: De Caterina
authors.affiliation: Postgraduate Medical School, University of Hertfordshire, Hertfordshire, UK.|National Heart & Lung Institute, Imperial College, London, UK.
authors.forename: Diana A
authors.initials: DA
authors.lastname: Gorog
authors.affiliation: Department of Cardiology and Angiology I, University Heart Center Freiburg, Freiburg, Germany.
authors.forename: Ingo
authors.initials: I
authors.lastname: Ahrens
authors.affiliation: Department of Cardiology, University Hospital Tübingen, Tübingen, Germany.
authors.forename: Tobias
authors.initials: T
authors.lastname: Geisler
authors.affiliation: Inova Center for Thrombosis Research and Drug Development, Inova Heart and Vascular Institute, Fairfax, VA, USA.
authors.forename: Paul A
authors.initials: PA
authors.lastname: Gurbel
authors.affiliation: Inova Center for Thrombosis Research and Drug Development, Inova Heart and Vascular Institute, Fairfax, VA, USA.
authors.forename: Udaya
authors.initials: U
authors.lastname: Tantry
authors.affiliation: Department of Internal Medicine, Division of Cardiology, Pulmonology and Vascular Medicine, Heinrich-Heine-University, Düsseldorf, Germany.
authors.forename: Eliano P
authors.initials: EP
authors.lastname: Navarese
authors.affiliation: Department of Cardiology, Medical University of Vienna, Vienna, Austria.
authors.forename: Jolanta M
authors.initials: JM
authors.lastname: Siller-Matula
mesh_terms: D054058:Acute Coronary Syndrome / Q000097:blood / Q000175:diagnosis / Q000235:genetics / Q000628:therapy*; D001792:Blood Platelets / Q000187:drug effects* / Q000378:metabolism; D000066491:Clinical Decision-Making; D003328:Coronary Thrombosis / Q000097:blood / Q000175:diagnosis / Q000235:genetics / Q000517:prevention & control*; D065731:Cytochrome P-450 CYP2C19 / Q000235:genetics / Q000378:metabolism; D004351:Drug Resistance; D006470:Hemorrhage / Q000139:chemically induced; D006801:Humans; D018579:Patient Selection; D062645:Percutaneous Coronary Intervention / Q000009:adverse effects; D000071185:Pharmacogenomic Testing; D000071184:Pharmacogenomic Variants; D010975:Platelet Aggregation Inhibitors / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use*; D010979:Platelet Function Tests; D057285:Precision Medicine / Q000379:methods*; D058921:Purinergic P2Y Receptor Antagonists / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use*; D058925:Receptors, Purinergic P2Y12 / Q000097:blood / Q000187:drug effects*; D018570:Risk Assessment; D016896:Treatment Outcome
chemical_list: C548576:P2RY12 protein, human; D010975:Platelet Aggregation Inhibitors; D058921:Purinergic P2Y Receptor Antagonists; D058925:Receptors, Purinergic P2Y12; C045793:CYP2C19 protein, human; D065731:Cytochrome P-450 CYP2C19
keywords: ACS; Antiplatelet therapy; HPR; LPR; P2Y12 inhibitors; Precision medicine