Consensus and update on the definition of on-treatment platelet reactivity to adenosine diphosphate associated with ischemia and bleeding.
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 P2Y12 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 P2Y12 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.
Sinai Center for Thrombosis Research, Sinai Hospital of Baltimore, Baltimore, Maryland.
Udaya S
US
Tantry
Département de Cardiologie, Hôpital Universitaire Nord, Aix-Marseille University, Marseille, France.
Laurent
L
Bonello
Department of Cardiology, Heart Center Balatonfüred, Balatonfüred, Hungary.
Daniel
D
Aradi
Scripps Clinic and Scripps Translational Science Institute, La Jolla, California.
Matthew J
MJ
Price
Department of Internal Medicine, Gyeongsang National University Hospital, Gyeongsang National University, Jinju, South Korea.
Young-Hoon
YH
Jeong
Cardiovascular Research Center, University of Florida College of Medicine, Jacksonville, Florida.
Dominick J
DJ
Angiolillo
Cardiovascular Research and Education, Columbia University Medical Center/New York-Presbyterian Hospital, New York, New York.
Gregg W
GW
Stone
Wessex Cardiothoracic Unit, University Hospital, Southampton National Health Service Foundation Trust, Southampton, United Kingdom.
Nick
N
Curzen
Medizinische Klinik III, Kardiologie und Kreislauferkrankungen, Universitätsklinikum Tübingen, Tübingen, Germany.
Tobias
T
Geisler
Department of Cardiology, St. Antonius Hospital Nieuwegein, Nieuwegein, the Netherlands.
Jurrien
J
Ten Berg
Cardiovascular Research and Education, Columbia University Medical Center/New York-Presbyterian Hospital, New York, New York.
Ajay
A
Kirtane
Department of Cardiology, Medical University of Vienna, Vienna, Austria.
Jolanta
J
Siller-Matula
Department of Anesthesiology and Intensive Care Medicine, Medical University of Graz, Graz, Austria.
Elisabeth
E
Mahla
Duke Clinical Research Institute, Duke University School of Medicine, Durham, North Carolina.
Richard C
RC
Becker
Veterans Affairs Boston Healthcare System, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts.
Deepak L
DL
Bhatt
Interventional Cardiology, Medstar Washington Hospital Center, Washington, DC.
Ron
R
Waksman
The Duke Clinical Research Institute, Durham, North Carolina.
Sunil V
SV
Rao
Department of Cardiology, Patras University Hospital, Patras, Greece.
Dimitrios
D
Alexopoulos
Department of Medical and Surgical Critical Care, University of Florence, Florence, Italy.
Rossella
R
Marcucci
Department of Internal Medicine, Rehabilitation, and Geriatrics, Geneva Platelet Group, Geneva University Hospitals and School of Medicine, Geneva, Switzerland.
Jean-Luc
JL
Reny
Universitaets-Herzzentrum Freiburg-Bad Krozingen, Bad Krozingen, Germany.
Dietmar
D
Trenk
Department of Cardiology, Ludwig-Maximilians Universität München, Medizinische Klinik und Poliklinik I, Munich, Germany.
Dirk
D
Sibbing
Sinai Center for Thrombosis Research, Sinai Hospital of Baltimore, Baltimore, Maryland. Electronic address: pgurbel@lifebridgehealth.org.
Paul A
PA
Gurbel
D054058:Acute Coronary Syndrome / Q000628:therapy; D000244:Adenosine Diphosphate / Q000627:therapeutic use*; D015906:Angioplasty, Balloon, Coronary; D001792:Blood Platelets / Q000187:drug effects; D003324:Coronary Artery Disease / Q000628:therapy; D003328:Coronary Thrombosis / Q000209:etiology / Q000517:prevention & control; D006470:Hemorrhage / Q000209:etiology*; D006801:Humans; D017202:Myocardial Ischemia / Q000209:etiology*; D010975:Platelet Aggregation Inhibitors / Q000627:therapeutic use*; D010979:Platelet Function Tests; D058921:Purinergic P2Y Receptor Antagonists / Q000627:therapeutic use*; D058925:Receptors, Purinergic P2Y12 / Q000187:drug effects; D018570:Risk Assessment; D012307:Risk Factors; D015607:Stents / Q000009:adverse effects
D010975:Platelet Aggregation Inhibitors; D058921:Purinergic P2Y Receptor Antagonists; D058925:Receptors, Purinergic P2Y12; D000244:Adenosine Diphosphate
ACS; ADP; CABG; CAD; CI; HPR; HR; LPR; MI; OR; P2Y(12) reaction units; PCI; PFT; PR; PRI; PRU; ROC; ST; TIMI; Thrombolysis In Myocardial Infarction; VASP-P; acute coronary syndrome(s); adenosine diphosphate; bleeding; confidence interval; consensus; coronary artery bypass graft; coronary artery disease; hazard ratio; high platelet reactivity to adenosine diphosphate; ischemia; low platelet reactivity to adenosine diphosphate; myocardial infarction; odds ratio; percutaneous coronary intervention; platelet function testing/test; platelet reactivity; platelet reactivity index; receiver-operating characteristic; stent thrombosis; vasodilator-stimulated phosphoprotein-phosphorylation