title: Bleeding and stent thrombosis on P2Y12-inhibitors: collaborative analysis on the role of platelet reactivity for risk stratification after percutaneous coronary intervention.
abstract: OBJECTIVE
  Although platelet reactivity during P2Y12-inhibitors is associated with stent thrombosis (ST) and bleeding, standardized and clinically validated thresholds for accurate risk stratification after percutaneous coronary intervention (PCI) are lacking. We sought to determine the prognostic value of low platelet reactivity (LPR), optimal platelet reactivity (OPR), or high platelet reactivity (HPR) by applying uniform cut-off values for standardized devices.
  
  
  RESULTS
  Authors of studies published before January 2015, reporting associations between platelet reactivity, ST, and major bleeding were contacted for a collaborative analysis using consensus-defined, uniform cut-offs for standardized platelet function assays. Based on best available evidence for each device (exploratory studies), LPR-OPR-HPR categories were defined as <95, 95-208, and >208 PRU for VerifyNow, <19, 19-46, and >46 U for the Multiplate analyser and <16, 16-50, and >50% for VASP assay. Seventeen studies including 20 839 patients were used for the analysis; 97% were treated with clopidogrel and 3% with prasugrel. Patients with HPR had significantly higher risk for ST [risk ratio (RR) and 95% CI: 2.73 (2.03-3.69), P < 0.00001], yet a slight reduction in bleeding [RR: 0.84 (0.71-0.99), P = 0.04] compared with those with OPR. In contrast, patients with LPR had a higher risk for bleeding [RR: 1.74 (1.47-2.06), P < 0.00001], without any further benefit in ST [RR: 1.06 (0.68-1.65), P = 0.78] in contrast to OPR. Mortality was significantly higher in patients with HPR compared with other categories (P < 0.05). Validation cohorts (n = 14) confirmed all results of exploratory studies (n = 3).
  
  
  CONCLUSIONS
  Platelet reactivity assessment during thienopyridine-type P2Y12-inhibitors identifies PCI-treated patients at higher risk for mortality and ST (HPR) or at an elevated risk for bleeding (LPR).
authors.affiliation: Department of Cardiology, Heart Center Balatonfüred and Semmelweis University, Heart and Vascular Center, 2 Gyogy Ter Balatonfüred, Budapest 8230, Hungary daniel_aradi@yahoo.com.
authors.forename: Dániel
authors.initials: D
authors.lastname: Aradi
authors.affiliation: Columbia University Medical Center/New York-Presbyterian Hospital and the Cardiovascular Research Foundation, New York, NY, USA.
authors.forename: Ajay
authors.initials: A
authors.lastname: Kirtane
authors.affiliation: Département de Cardiologie, Hôpital Universitaire Nord, Aix-Marseille University, Marseille, France.
authors.forename: Laurent
authors.initials: L
authors.lastname: Bonello
authors.affiliation: Sinai Center for Thrombosis Research, Sinai Hospital of Baltimore, Baltimore, MD, USA.
authors.forename: Paul A
authors.initials: PA
authors.lastname: Gurbel
authors.affiliation: Sinai Center for Thrombosis Research, Sinai Hospital of Baltimore, Baltimore, MD, USA.
authors.forename: Udaya S
authors.initials: US
authors.lastname: Tantry
authors.affiliation: 3rd Department of Internal Medicine, Cardiology and Emergency Medicine, Wilhelminen Hospital, Vienna, Austria.
authors.forename: Kurt
authors.initials: K
authors.lastname: Huber
authors.affiliation: 3rd Department of Internal Medicine, Cardiology and Emergency Medicine, Wilhelminen Hospital, Vienna, Austria.
authors.forename: Matthias K
authors.initials: MK
authors.lastname: Freynhofer
authors.affiliation: Department of Cardiology, St. Antonius Hospital, Nieuwegein, Netherlands.
authors.forename: Jurrien
authors.initials: J
authors.lastname: ten Berg
authors.affiliation: Department of Cardiology, St. Antonius Hospital, Nieuwegein, Netherlands.
authors.forename: Paul
authors.initials: P
authors.lastname: Janssen
authors.affiliation: Cardiovascular Research Center, University of Florida College of Medicine, Jacksonville, FL, USA.
authors.forename: Dominick J
authors.initials: DJ
authors.lastname: Angiolillo
authors.affiliation: Department of Cardiology, Medical University of Vienna, Vienna, Austria.
authors.forename: Jolanta M
authors.initials: JM
authors.lastname: Siller-Matula
authors.affiliation: Department of Medical and Surgical Critical Care, University of Florence, Florence, Italy.
authors.forename: Rossella
authors.initials: R
authors.lastname: Marcucci
authors.affiliation: Department of Cardiovascular Sciences, Campus Bio-Medico University of Rome, Rome, Italy.
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Patti
authors.affiliation: Department of Cardiovascular Sciences, Campus Bio-Medico University of Rome, Rome, Italy.
authors.forename: Fabio
authors.initials: F
authors.lastname: Mangiacapra
authors.affiliation: Thoraxcenter, Erasmus Medical Center, Rotterdam, The Netherlands.
authors.forename: Marco
authors.initials: M
authors.lastname: Valgimigli
authors.affiliation: Pôle d'activité médico-chirurgicale Cardiovasculaire, Nouvel Hôpital Civil, Université de Strasbourg, Strasbourg, France.
authors.forename: Olivier
authors.initials: O
authors.lastname: Morel
authors.affiliation: Cardiovascular Department, Policlinico S. Orsola, Bologna, Italy.
authors.forename: Tullio
authors.initials: T
authors.lastname: Palmerini
authors.affiliation: Scripps Clinic and Scripps Translational Science Institute, La Jolla, CA, USA.
authors.forename: Matthew J
authors.initials: MJ
authors.lastname: Price
authors.affiliation: Département de Cardiologie, CHU Timone, Marseille F-13385, France.
authors.forename: Thomas
authors.initials: T
authors.lastname: Cuisset
authors.affiliation: Department of Cardiology, Deutsches Herzzentrum München, Technische Universität München, Munich, Germany Medizinische Klinik, Klinikum rechts der Isar, Technische Universität München, Munich, Germany DZHK (German Center for Cardiovascular Research), Partner Site Munich Heart Alliance, Munich, Germany.
authors.forename: Adnan
authors.initials: A
authors.lastname: Kastrati
authors.affiliation: Columbia University Medical Center/New York-Presbyterian Hospital and the Cardiovascular Research Foundation, New York, NY, USA.
authors.forename: Gregg W
authors.initials: GW
authors.lastname: Stone
authors.affiliation: DZHK (German Center for Cardiovascular Research), Partner Site Munich Heart Alliance, Munich, Germany Medizinische Klinik und Poliklinik I, Klinikum der Universität München, Ludwig-Maximilians-Universität München, Munich, Germany.
authors.forename: Dirk
authors.initials: D
authors.lastname: Sibbing
mesh_terms: D000368:Aged; D000077144:Clopidogrel; D005260:Female; D006083:Graft Occlusion, Vascular / Q000209:etiology / Q000401:mortality / Q000517:prevention & control; D006470:Hemorrhage / Q000139:chemically induced* / Q000401:mortality / Q000517:prevention & control; D006801:Humans; D008297:Male; D062645:Percutaneous Coronary Intervention / Q000009:adverse effects* / Q000401:mortality; D015539:Platelet Activation / Q000187:drug effects*; D010975:Platelet Aggregation Inhibitors / Q000009:adverse effects; D000068799:Prasugrel Hydrochloride / Q000009:adverse effects; D058921:Purinergic P2Y Receptor Antagonists / Q000009:adverse effects*; D018570:Risk Assessment; D015607:Stents; D013927:Thrombosis / Q000139:chemically induced* / Q000401:mortality / Q000517:prevention & control; D013988:Ticlopidine / Q000009:adverse effects / Q000031:analogs & derivatives
chemical_list: D010975:Platelet Aggregation Inhibitors; D058921:Purinergic P2Y Receptor Antagonists; D000077144:Clopidogrel; D000068799:Prasugrel Hydrochloride; D013988:Ticlopidine
keywords: P2Y12-inhibitors; Platelet reactivity; Stent thrombosis, Bleeding