title: Effects of nebivolol on biomarkers in elderly patients with heart failure.
abstract: BACKGROUND
  Heart failure activates neurohormones, and elevated levels of brain natriuretic peptide (BNP) are associated with adverse outcomes. The SENIORS trial showed that nebivolol, a highly selective beta-1 antagonist with vasodilating properties, reduced the composite outcome of all cause mortality or cardiovascular hospital admissions in older patients with heart failure. We explored the effects of nebivolol on a range of neurohormones, cytokines and markers of nitric oxide activity in heart failure.
  
  
  METHODS
  In a subset of patients in SENIORS we measured N-terminal pro-brain natriuretic peptide (NT-BNP), pro atrial natriuretic peptide (Pro-ANP), endothelin-1 (ET-1), peripheral norepinephrine (PNE), soluble Fas (sFas), soluble Fas-ligand (sFas-L), tumour necrosis factor-alpha (TNF-α), serum uric acid (SUA), symmetrical dimethyl arginine (SDMA), arginine, citrulline and asymmetrical dimethyl arginine (ADMA) at baseline (before study drug), at 6 months and 12 months in a prespecified substudy.
  
  
  RESULTS
  One hundred and six patients were enrolled and 75 had a baseline and at least one follow-up sample. There were no significant differences in neurohormone cytokines or nitric oxide markers measured between the two groups at six or twelve months. NT-ProBNP showed a numerical increase in the nebivolol group compared to placebo (P=0.08) and sFas showed a numerical increase in patients on placebo (P=0.08). Mean baseline LVEF was 35% in both groups and at 12 months was 43% on nebivolol group and 34% on placebo group (P=0.01).
  
  
  CONCLUSIONS
  There were trends but no clear changes associated with nebivolol in neurohormones, cytokines or markers of nitric oxide activity in this study of elderly patients with heart failure. Further studies are needed to understand the mechanistic effects of beta blockers on biomarkers in heart failure.
authors.affiliation: Whipps Cross University Hospital, Barts Health NHS Trust, London, UK. Electronic address: aniltaneja00@hotmail.com.
authors.forename: Anil K
authors.initials: AK
authors.lastname: Taneja
authors.affiliation: Department of Chemical Pathology, St. George's Hospital, London, UK.
authors.forename: David
authors.initials: D
authors.lastname: Gaze
authors.affiliation: Monash University, Australia; Melbourne University, Australia; Warwick University, UK.
authors.forename: Andrew J S
authors.initials: AJ
authors.lastname: Coats
authors.affiliation: Cluj-Napoca University Hospital, Romania.
authors.forename: Dan
authors.initials: D
authors.lastname: Dumitrascu
authors.affiliation: 1st Internal Cardioangiological Dept, St. Anne's Hospital & Medical Faculty, Brno, Czech Republic.
authors.forename: Lenka
authors.initials: L
authors.lastname: Spinarova
authors.affiliation: Cardiovascular Markers, St. George's Hospital University, London, UK.
authors.forename: Paul
authors.initials: P
authors.lastname: Collinson
authors.affiliation: Novartis, Basel, Switzerland.
authors.forename: Michael
authors.initials: M
authors.lastname: Roughton
authors.affiliation: Norwich Medical School, University of East Anglia, UK; Previously Royal Brompton and Harefield NHS Foundation Trust/Imperial College, London, UK.
authors.forename: Marcus D
authors.initials: MD
authors.lastname: Flather
mesh_terms: D058671:Adrenergic beta-1 Receptor Antagonists / Q000627:therapeutic use*; D000368:Aged; D000369:Aged, 80 and over; D001578:Benzopyrans / Q000627:therapeutic use*; D015415:Biomarkers / Q000097:blood; D016207:Cytokines / Q000097:blood*; D004311:Double-Blind Method; D004983:Ethanolamines / Q000627:therapeutic use*; D005260:Female; D006333:Heart Failure / Q000097:blood* / Q000188:drug therapy*; D006801:Humans; D038622:Internationality; D008297:Male; D000068577:Nebivolol; D018377:Neurotransmitter Agents / Q000097:blood; D016896:Treatment Outcome
chemical_list: D058671:Adrenergic beta-1 Receptor Antagonists; D001578:Benzopyrans; D015415:Biomarkers; D016207:Cytokines; D004983:Ethanolamines; D018377:Neurotransmitter Agents; D000068577:Nebivolol
keywords: Beta blockers in heart failure; NT-Pro BNP and beta blockers; Nebivolol; Neurohormones; SENIORS substudy