title: Effect of serelaxin on cardiac, renal, and hepatic biomarkers in the Relaxin in Acute Heart Failure (RELAX-AHF) development program: correlation with outcomes.
abstract: OBJECTIVE
  The aim of this study was to assess the effects of serelaxin on short-term changes in markers of organ damage and congestion and relate them to 180-day mortality in patients with acute heart failure.
  
  
  BACKGROUND
  Hospitalization for acute heart failure is associated with high post-discharge mortality, and this may be related to organ damage.
  
  
  METHODS
  The Pre-RELAX-AHF (Relaxin in Acute Heart Failure) phase II study and RELAX-AHF phase III study were international, multicenter, double-blind, placebo-controlled trials in which patients hospitalized for acute heart failure were randomized within 16 h to intravenous placebo or serelaxin. Each patient was followed daily to day 5 or discharge and at days 5, 14, and 60 after enrollment. Vital status was assessed through 180 days. In RELAX-AHF, laboratory evaluations were performed daily to day 5 and at day 14. Plasma levels of biomarkers were measured at baseline and days 2, 5, and 14. All-cause mortality was assessed as a safety endpoint in both studies.
  
  
  RESULTS
  Serelaxin reduced 180-day mortality, with similar effects in the phase II and phase III studies (combined studies: N = 1,395; hazard ratio: 0.62; 95% confidence interval: 0.43 to 0.88; p = 0.0076). In RELAX-AHF, changes in markers of cardiac (high-sensitivity cardiac troponin T), renal (creatinine and cystatin-C), and hepatic (aspartate transaminase and alanine transaminase) damage and of decongestion (N-terminal pro-brain natriuretic peptide) at day 2 and worsening heart failure during admission were associated with 180-day mortality. Serelaxin administration improved these markers, consistent with the prevention of organ damage and faster decongestion.
  
  
  CONCLUSIONS
  Early administration of serelaxin was associated with a reduction of 180-day mortality, and this occurred with fewer signs of organ damage and more rapid relief of congestion during the first days after admission.
authors.affiliation: Cardiology, Department of Medical and Surgical Specialties, Radiological Sciences, and Public Health, University of Brescia and Civil Hospital, Brescia, Italy. metramarco@libero.it
authors.forename: Marco
authors.initials: M
authors.lastname: Metra
authors.forename: Gad
authors.initials: G
authors.lastname: Cotter
authors.forename: Beth A
authors.initials: BA
authors.lastname: Davison
authors.forename: G Michael
authors.initials: GM
authors.lastname: Felker
authors.forename: Gerasimos
authors.initials: G
authors.lastname: Filippatos
authors.forename: Barry H
authors.initials: BH
authors.lastname: Greenberg
authors.forename: Piotr
authors.initials: P
authors.lastname: Ponikowski
authors.forename: Elaine
authors.initials: E
authors.lastname: Unemori
authors.forename: Adriaan A
authors.initials: AA
authors.lastname: Voors
authors.forename: Kirkwood F
authors.initials: KF
authors.lastname: Adams
authors.forename: Maria I
authors.initials: MI
authors.lastname: Dorobantu
authors.forename: Liliana
authors.initials: L
authors.lastname: Grinfeld
authors.forename: Guillaume
authors.initials: G
authors.lastname: Jondeau
authors.forename: Alon
authors.initials: A
authors.lastname: Marmor
authors.forename: Josep
authors.initials: J
authors.lastname: Masip
authors.forename: Peter S
authors.initials: PS
authors.lastname: Pang
authors.forename: Karl
authors.initials: K
authors.lastname: Werdan
authors.forename: Margaret F
authors.initials: MF
authors.lastname: Prescott
authors.forename: Christopher
authors.initials: C
authors.lastname: Edwards
authors.forename: Sam L
authors.initials: SL
authors.lastname: Teichman
authors.forename: Angelo
authors.initials: A
authors.lastname: Trapani
authors.forename: Christopher A
authors.initials: CA
authors.lastname: Bush
authors.forename: Rajnish
authors.initials: R
authors.lastname: Saini
authors.forename: Christoph
authors.initials: C
authors.lastname: Schumacher
authors.forename: Thomas
authors.initials: T
authors.lastname: Severin
authors.forename: John R
authors.initials: JR
authors.lastname: Teerlink
mesh_terms: D000208:Acute Disease; D000410:Alanine Transaminase / Q000097:blood; D001219:Aspartate Aminotransferases / Q000097:blood; D015415:Biomarkers / Q000097:blood*; D003404:Creatinine / Q000097:blood; D055316:Cystatin C / Q000097:blood; D004311:Double-Blind Method; D006333:Heart Failure / Q000097:blood / Q000188:drug therapy* / Q000401:mortality; D006760:Hospitalization; D006801:Humans; D007668:Kidney / Q000187:drug effects* / Q000378:metabolism; D008099:Liver / Q000187:drug effects* / Q000378:metabolism; D020097:Natriuretic Peptide, Brain / Q000097:blood; D010446:Peptide Fragments / Q000097:blood; D011994:Recombinant Proteins / Q000008:administration & dosage / Q000494:pharmacology; D012065:Relaxin / Q000008:administration & dosage / Q000494:pharmacology*; D015996:Survival Rate; D016896:Treatment Outcome; D020107:Troponin T / Q000097:blood
chemical_list: D015415:Biomarkers; D055316:Cystatin C; D010446:Peptide Fragments; D011994:Recombinant Proteins; D020107:Troponin T; C109794:pro-brain natriuretic peptide (1-76); C577649:serelaxin protein, human; D020097:Natriuretic Peptide, Brain; D012065:Relaxin; D003404:Creatinine; D001219:Aspartate Aminotransferases; D000410:Alanine Transaminase