@article{958c885bf42e4326b56abb89877e7764,
title = "Consensus and update on the definition of on-treatment platelet reactivity to adenosine diphosphate associated with ischemia and bleeding",
abstract = "Dual antiplatelet therapy with aspirin and a P2Y12 receptor blocker is a key strategy to reduce platelet reactivity and to prevent thrombotic events in patients treated with percutaneous coronary intervention. In an earlier consensus document, we proposed cutoff values for high on-treatment platelet reactivity to adenosine diphosphate (ADP) associated with post-percutaneous coronary intervention ischemic events for various platelet function tests (PFTs). Updated American and European practice guidelines have issued a Class IIb recommendation for PFT to facilitate the choice of P2Y 12 receptor inhibitor in selected high-risk patients treated with percutaneous coronary intervention, although routine testing is not recommended (Class III). Accumulated data from large studies underscore the importance of high on-treatment platelet reactivity to ADP as a prognostic risk factor. Recent prospective randomized trials of PFT did not demonstrate clinical benefit, thus questioning whether treatment modification based on the results of current PFT platforms can actually influence outcomes. However, there are major limitations associated with these randomized trials. In addition, recent data suggest that low on-treatment platelet reactivity to ADP is associated with a higher risk of bleeding. Therefore, a therapeutic window concept has been proposed for P2Y 12 inhibitor therapy. In this updated consensus document, we review the available evidence addressing the relation of platelet reactivity to thrombotic and bleeding events. In addition, we propose cutoff values for high and low on-treatment platelet reactivity to ADP that might be used in future investigations of personalized antiplatelet therapy.",
keywords = "adenosine diphosphate, bleeding, consensus, ischemia, platelet reactivity",
author = "Tantry, {Udaya S.} and Laurent Bonello and Daniel Aradi and Price, {Matthew J.} and Jeong, {Young Hoon} and Angiolillo, {Dominick J.} and Stone, {Gregg W.} and Nick Curzen and Tobias Geisler and {Ten Berg}, Jurrien and Ajay Kirtane and Jolanta Siller-Matula and Elisabeth Mahla and Becker, {Richard C.} and Bhatt, {Deepak L.} and Ron Waksman and Rao, {Sunil V.} and Dimitrios Alexopoulos and Rossella Marcucci and Reny, {Jean Luc} and Dietmar Trenk and Dirk Sibbing and Gurbel, {Paul A.}",
note = "Funding Information: Dr. Tantry has received payment for lectures and travel support from Accumetrics. Dr. Bonello has received lecture and consulting fees from sanofi-aventis, AstraZeneca, and Eli Lilly; and grants from Assistance Publique Hopitaux de Marseille and AstraZeneca . Dr. Aradi has received consulting fees from Verum Diagnostica; and lecture fees from Verum Diagnostica, Roche, DSI/Lilly, AstraZeneca, Pfizer, Bayer AG, Abbott, and Krka. Dr. Price has received speaking fees from AstraZeneca and Daiichi Sankyo/Lilly & Co.; consulting fees from AstraZeneca, Daiichi Sankyo/Lilly & Co., Janssen Pharmaceuticals, Accumetrics, The Medicines Company, Merck & Co., Inc., Medicure, Boston Scientific, Bristol-Myers Squibb/sanofi-aventis, Terumo, and St. Jude Medical; and equity interest in Iverson Genetics. Dr. Jeong has received honoraria for lectures from sanofi-aventis, Daiichi Sankyo/Lilly, Nanosphere, Haemonetics, and Otsuka; and research grants or support from Dong-A Pharmaceuticals , Han-mi Pharmaceuticals , Boehringer-Ingelheim , Otsuka , Accumetrics , and Haemonetics . Dr. Angiolillo has received consulting fees or honoraria from Bristol-Myers Squibb, sanofi-aventis, Eli Lilly, Daiichi Sankyo, The Medicines Company, AstraZeneca, Merck & Co., Inc., Evolva, Abbott Vascular, and PLx Pharma; payment for participation in review activities from Johnson & Johnson, St. Jude Medical, and Sunovion; institutional payments for grants from Bristol-Myers Squibb, sanofi-aventis, GlaxoSmithKline, Otsuka, Eli Lilly, Daiichi Sankyo, The Medicines Company, AstraZeneca, and Evolva ; and he has received an Esther and King Biomedical Research Grant. Dr. Stone has received consulting fees from Boston Scientific, Eli Lilly, Daiichi Sankyo, and AstraZeneca. Dr. Curzen has received unrestricted grants from Haemonetics, St. Jude Medical, and Medtronic ; and speaker/consulting fees from Haemonetics, St. Jude Medical, Boston Scientific, Medtronic, Abbott Vascular, and Daiichi Sankyo/Lilly. Dr. Geisler has received consulting fees from Daiichi Sankyo, Lilly, Bayer, and AstraZeneca; lecture fees from Bayer, Daiichi Sankyo, and The Medicines Company; and restricted grants from Daiichi Sankyo, The Medicines Company, and Siemens Healthcare . Dr. ten Berg has received lecture and consulting fees from AstraZeneca, Merck & Co., Inc., Eli Lilly, and Daiichi Sankyo. Dr. Siller-Matula has received lecture or consulting fees from AstraZeneca, Daiichi Sankyo, and Eli Lilly; and has received a research grant from Roche Diagnostics . Dr. Mahla has received study grants from CSL Behring Biotherapies for Life and NovoNordisk Pharma ; and has received lecture fees from CSL Behring Biotherapies for Life and Boehringer Ingelheim. Dr. Becker has received research support from AstraZeneca and the National Heart, Lung and Blood Institutes ; educational grants from Pfizer and AstraZeneca ; and honoraria for his service on the scientific advisory boards for Daiichi-Sankyo and Portola. Dr. Bhatt serves on the advisory boards of Elsevier Practice Update Cardiology, Medscape Cardiology, and Regado Biosciences; he is the on board of directors of Boston VA Research Institute and Society of Cardiovascular Patient Care; he is the chair of the American Heart Association Get With The Guidelines Science Subcommittee; he has received honoraria from American College of Cardiology (editor, Clinical Trials, Cardiosource), Duke Clinical Research Institute (clinical trial steering committees), Slack Publications (chief medical editor, Cardiology Today Intervention), WebMD (continuing medical education steering committees); he is a senior associate editor for Journal of Invasive Cardiology; he sits on the data monitoring committees of the COMPLETE (Complete Versus Culprit Revascularization in STEMI), and TOTAL (A Randomized Trial of Routine Aspiration Thrombectomy With PCI Versus PCI Alone in Patients With STEMI Undergoing Primary PCI) studies; he has received research grants from Amarin, AstraZeneca, Bristol-Myers Squibb, Eisai, Ethicon, Medtronic, sanofi-aventis, The Medicines Company ; and he has performed unfunded research for FlowCo, PLx Pharma, and Takeda. Dr. Rao has received research funding from Ikaria and sanofi-aventis ; and consulting fees/honoraria from AstraZeneca, Daiichi Sankyo Lilly, The Medicines Company, Terumo Medical, and ZOLL. Dr. Alexopoulos has received lecture fees from AstraZeneca. Dr. Marcucci has received consulting fees from Merck & Co., Inc., and Haemonetics; and lecture fees from AstraZeneca, Eli Lilly, Sharp, Dohme, and Instrumentation Laboratory. Dr. Reny has received lectures fees from Merck Sharp & Dohme. Dr. Trenk has received consulting fees from Boehringer Ingelheim, Daiichi Sankyo, and Eli Lilly; lecture fees from AstraZeneca, Bayer Vital, Daiichi Sankyo, Eli Lilly, and Merck Sharp & Dohme; and an institutional grant from Eli Lilly. Dr. Sibbing has received consulting fees from Daiichi Sankyo, Eli Lilly, and Verum Diagnostica; and lecture fees from Roche and CSL Behring. Dr. Gurbel has received consulting fees from Daiichi Sankyo, Lilly, Pozen, Novartis, Bayer, AstraZeneca, Accumetrics, Nanosphere, sanofi-aventis, Boehringer Ingelheim, Merck & Co., Inc., Medtronic, Iverson Genetics, CSL, and Haemonetics; grants from the National Institutes of Health, Daiichi Sankyo, Lilly, Pozen, CSL, AstraZeneca, sanofi-aventis, Haemoscope, Medtronic, Harvard Clinical Research Institute, and Duke Clinical Research Institute ; lecture fees, including service on Speakers' Bureaus, from Lilly, Daiichi Sankyo, Nanosphere, sanofi-aventis, Merck, and Iverson Genetics; and payment for development of educational presentations from Schering-Plough, the Discovery Channel, and Pri-Med. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose. ",
year = "2013",
month = dec,
day = "17",
doi = "10.1016/j.jacc.2013.07.101",
language = "English",
volume = "62",
pages = "2261--2273",
journal = "Journal of the American College of Cardiology",
issn = "0735-1097",
publisher = "Elsevier USA",
number = "24",
}