title: Prognostic performance of multiple biomarkers in patients with non-ST-segment elevation acute coronary syndrome: analysis from the MERLIN-TIMI 36 trial (Metabolic Efficiency With Ranolazine for Less Ischemia in Non-ST-Elevation Acute Coronary Syndromes-Thrombolysis In Myocardial Infarction 36).
abstract: OBJECTIVE
  The aim of this study was to assess the prognostic performance of C-terminal provasopressin (copeptin), midregional pro-adrenomedullin (MR-proADM), and midregional pro-atrial natriuretic peptide (MR-proANP) in a large prospective cohort of patients with non-ST-segment elevation acute coronary syndrome (NSTE-ACS).
  
  
  BACKGROUND
  Copeptin, MR-proADM, and MR-proANP are emerging biomarkers of hemodynamic stress that have been associated with adverse cardiovascular (CV) outcomes in heart failure (HF) and stable ischemic disease.
  
  
  METHODS
  We measured copeptin, MR-proADM, and MR-proANP concentrations in 4,432 patients with NSTE-ACS who were randomized to treatment with ranolazine or placebo in the MERLIN-TIMI 36 (Metabolic Efficiency With Ranolazine for Less Ischemia in Non-ST-Elevation Acute Coronary Syndromes-Thrombolysis In Myocardial Infarction 36) trial and followed up for 1 year.
  
  
  RESULTS
  A high concentration (quartile 4 vs. quartiles 1 to 3) of each biomarker identified an increased risk of CV death or HF(copeptin: 13.2% vs. 5.0%, p < 0.001; MR-proADM: 15.8% vs. 4.1%, p < 0.001; MR-proANP: 17.7% vs. 3.5%, p < 0.001)as well as CV death, HF, and myocardial infarction individually (all p ≤ 0.001). After adjustment for important covariates, each biomarker remained associated with CV death or HF at 1 year (adjusted hazard ratio: copeptin, 1.71; MR-proADM, 1.96; MR-proANP, 2.20; all p ≤ 0.001).These biomarkers improved prognostic discrimination and patient re-classification for CV death or HF at 1 year(all categorical NRI >10%, p < 0.001), and maintained independent association with composite CV death or HF when concurrently assessed in a model with clinical indicators plus BNP, cTnI, ST2, PAPP-A, and MPO (each p≤0.01) [corrected].
  
  
  CONCLUSIONS
  Copeptin, MR-proADM, and MR-proANP are complementary prognostic markers for CV death and HF in patients with NSTE-ACS that perform as well as or better than established and other emerging biomarkers and warrant further investigation of application for therapeutic decision making. (Metabolic Efficiency With Ranolazine for Less Ischemia in Non-ST Elevation Acute Coronary Syndromes; NCT00099788).
authors: TIMI Study Group, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts.
authors: Ryan G
authors: RG
authors: O'Malley
authors: TIMI Study Group, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts; Cardiovascular Division, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts. Electronic address: mbonaca@partners.org.
authors: Marc P
authors: MP
authors: Bonaca
authors: TIMI Study Group, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts; Cardiovascular Division, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts.
authors: Benjamin M
authors: BM
authors: Scirica
authors: TIMI Study Group, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts.
authors: Sabina A
authors: SA
authors: Murphy
authors: Department of Pathology, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts.
authors: Petr
authors: P
authors: Jarolim
authors: TIMI Study Group, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts; Cardiovascular Division, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts.
authors: Marc S
authors: MS
authors: Sabatine
authors: TIMI Study Group, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts; Cardiovascular Division, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts.
authors: Eugene
authors: E
authors: Braunwald
authors: TIMI Study Group, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts; Cardiovascular Division, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts.
authors: David A
authors: DA
authors: Morrow
mesh_terms: D000083:Acetanilides / Q000008:administration & dosage*; D054058:Acute Coronary Syndrome / Q000097:blood / Q000188:drug therapy* / Q000503:physiopathology; D000368:Aged; D009320:Atrial Natriuretic Factor / Q000097:blood; D015415:Biomarkers / Q000097:blood*; D004562:Electrocardiography; D004791:Enzyme Inhibitors / Q000008:administration & dosage; D005260:Female; D005500:Follow-Up Studies; D006020:Glycopeptides / Q000097:blood; D006801:Humans; D008297:Male; D010879:Piperazines / Q000008:administration & dosage*; D011379:Prognosis; D011446:Prospective Studies; D011498:Protein Precursors; D000069458:Ranolazine; D012307:Risk Factors; D026941:Sodium Channel Blockers; D015912:Thrombolytic Therapy / Q000379:methods*; D013997:Time Factors; D016896:Treatment Outcome
chemical_list: D000083:Acetanilides; D015415:Biomarkers; D004791:Enzyme Inhibitors; D006020:Glycopeptides; D010879:Piperazines; D011498:Protein Precursors; D026941:Sodium Channel Blockers; C048197:copeptins; C552580:midregional pro-atrial natriuretic peptide, human; D009320:Atrial Natriuretic Factor; D000069458:Ranolazine
keywords: acute coronary syndromes(s); cardiac biomarkers; ischemic heart disease; risk prediction