title: Biomarkers in relation to the effects of ticagrelor in comparison with clopidogrel in non-ST-elevation acute coronary syndrome patients managed with or without in-hospital revascularization: a substudy from the Prospective Randomized Platelet Inhibition and Patient Outcomes (PLATO) trial.
abstract: BACKGROUND
  Risk stratification and the use of specific biomarkers have been proposed for tailoring treatment in patients with non-ST-elevation acute coronary syndrome (NSTE-ACS). We investigated the prognostic importance of high-sensitivity troponin T (hs-TnT), N-terminal pro-brain natriuretic peptide (NT-proBNP), and growth differentiation factor-15 (GDF-15) in relation to randomized treatment (ticagrelor versus clopidogrel) and management strategy (with or without revascularization) in the NSTE-ACS subgroup of the Platelet Inhibition and Patient Outcomes (PLATO) trial.
  
  
  RESULTS
  Of 18 624 patients in the PLATO trial, 9946 had an entry diagnosis of NSTE-ACS and baseline blood samples available. During index hospitalization, 5357 were revascularized, and 4589 were managed without revascularization. Hs-TnT, NT-proBNP, and GDF-15 were determined and assessed according to predefined cutoff levels. Median follow-up was 9.1 months. Increasing levels of hs-TnT were associated with increasing risk of cardiovascular death, myocardial infarction, and stroke in medically managed patients (P<0.001), but not in those managed invasively. NT-proBNP and GDF-15 levels were associated with the same events independent of management strategy. Ticagrelor versus clopidogrel reduced the rate of cardiovascular death, myocardial infarction, and stroke in patients with NSTE-ACS and hs-TnT ≥14.0 ng/L in both invasively and noninvasively managed patients; in patients with hs-TnT <14.0 ng/L, there was no difference between ticagrelor and clopidogrel in the noninvasive group
  
  
  CONCLUSIONS
  Hs-TnT, NT-proBNP, and GDF-15 are predictors of cardiovascular death, myocardial infarction, and stroke in patients with NSTE-ACS managed noninvasively, and NT-proBNP and GDF-15 also in those managed invasively. Elevated hs-TnT predicts substantial benefit of ticagrelor over clopidogrel both in invasively and noninvasively managed patients, but no apparent benefit was seen at normal hs-TnT.
  
  
  BACKGROUND
  URL:http://www.clinicaltrials.gov. Unique identifier: NCT00391872.
authors.affiliation: Department of Medical Sciences, Cardiology and Uppsala Clinical Research Center, Uppsala University, Uppsala, Sweden (L.W., D.L., L.W., C.H., S.K.J.); Department of Medical Sciences, Clinical Chemistry and Uppsala Clinical Research Center Uppsala University, Uppsala, Sweden (A.S.); Division of Cardiovascular Health and Disease, Heart, Lung and Vascular Institute, Academic Health Center, Cincinnati, OH (R.C.B.); Department of Medicine, Stanford University, Stanford, CA (R.A.H., K.W.M.); TIMI Study Group, Cardiovascular Division, Brigham and Women's Hospital, Boston, MA (C.P.C.); Department of Cardiology, Medisch Centrum Alkmaar, Alkmaar, Netherlands (J.H.C.); AstraZeneca Research and Development, Mölndal, Sweden (A.H.); Medizinische Klinik, Universitätsklinikum Heidelberg, Heidelberg, Germany (E.G., H.A.K.); Medical Department, Hospital Unit West, Herning/Holstbro, Denmark (S.H.); INSERM-Unité 698, Paris, France; Assistance Publique-Hôpitaux de Paris, Département Hospitalo-Universitaire FIRE, Hôpital Bichat, Paris, France; Université Paris-Diderot, Sorbonne-Paris Cité, Paris, France; NHLI Imperial College, ICMS, Royal Brompton Hospital, London, UK (P.G.S.); and Department of Cardiovascular Science, University of Sheffield, Sheffield, UK (R.F.S.).
authors.forename: Lars
authors.initials: L
authors.lastname: Wallentin
authors.forename: Daniel
authors.initials: D
authors.lastname: Lindholm
authors.forename: Agneta
authors.initials: A
authors.lastname: Siegbahn
authors.forename: Lisa
authors.initials: L
authors.lastname: Wernroth
authors.forename: Richard C
authors.initials: RC
authors.lastname: Becker
authors.forename: Christopher P
authors.initials: CP
authors.lastname: Cannon
authors.forename: Jan H
authors.initials: JH
authors.lastname: Cornel
authors.forename: Anders
authors.initials: A
authors.lastname: Himmelmann
authors.forename: Evangelos
authors.initials: E
authors.lastname: Giannitsis
authors.forename: Robert A
authors.initials: RA
authors.lastname: Harrington
authors.forename: Claes
authors.initials: C
authors.lastname: Held
authors.forename: Steen
authors.initials: S
authors.lastname: Husted
authors.forename: Hugo A
authors.initials: HA
authors.lastname: Katus
authors.forename: Kenneth W
authors.initials: KW
authors.lastname: Mahaffey
authors.forename: Ph Gabriel
authors.initials: PG
authors.lastname: Steg
authors.forename: Robert F
authors.initials: RF
authors.lastname: Storey
authors.forename: Stefan K
authors.initials: SK
authors.lastname: James
mesh_terms: D054058:Acute Coronary Syndrome / Q000097:blood / Q000188:drug therapy / Q000401:mortality; D000241:Adenosine / Q000008:administration & dosage / Q000031:analogs & derivatives*; D015415:Biomarkers / Q000097:blood; D000077144:Clopidogrel; D004562:Electrocardiography; D055436:Growth Differentiation Factor 15 / Q000097:blood; D017052:Hospital Mortality; D006801:Humans; D053208:Kaplan-Meier Estimate; D009204:Myocardial Revascularization / Q000401:mortality*; D020097:Natriuretic Peptide, Brain / Q000097:blood; D010446:Peptide Fragments / Q000097:blood; D011237:Predictive Value of Tests; D011379:Prognosis; D011446:Prospective Studies; D058921:Purinergic P2Y Receptor Antagonists / Q000008:administration & dosage; D012307:Risk Factors; D000077486:Ticagrelor; D013988:Ticlopidine / Q000008:administration & dosage / Q000031:analogs & derivatives*; D020107:Troponin T / Q000097:blood
chemical_list: D015415:Biomarkers; C526140:GDF15 protein, human; D055436:Growth Differentiation Factor 15; D010446:Peptide Fragments; D058921:Purinergic P2Y Receptor Antagonists; D020107:Troponin T; C109794:pro-brain natriuretic peptide (1-76); D020097:Natriuretic Peptide, Brain; D000077144:Clopidogrel; D000077486:Ticagrelor; D000241:Adenosine; D013988:Ticlopidine
keywords: acute coronary syndrome; biological markers; blood platelets; myocardial infarction; troponin