title: Effect of serelaxin on mode of death in acute heart failure: results from the RELAX-AHF study.
abstract: BACKGROUND
  Little is known about mode of death after acute heart failure (AHF) hospitalization. In the RELAX-AHF (Efficacy and Safety of Relaxin for the Treatment of Acute Heart Failure) study, serelaxin, the recombinant form of human relaxin-2, reduced post-discharge mortality at 180 days in selected patients with AHF.
  
  
  OBJECTIVE
  The goal of this study was to assess the effect of serelaxin on specific modes of death in patients with AHF.
  
  
  METHODS
  The RELAX-AHF study randomized 1,161 patients with AHF to 48 h of therapy with intravenous serelaxin or placebo. Patients were followed for vital status through 180 days. A blinded clinical events committee reviewed all deaths and adjudicated a cause of death on the basis of pre-specified criteria. Cox proportional hazard models were used to assess the effect of serelaxin on each mode of death, on the basis of pre-specified groupings of mode of death.
  
  
  RESULTS
  There were 107 deaths (9.3%): 37 (35%) due to HF, 25 (23%) due to sudden death, 15 (14%) due to other cardiovascular (CV) causes, 19 (18%) due to non-CV causes, and 11 (10%) classified as unknown. The treatment effect of serelaxin was most pronounced on other CV deaths (hazard ratio [HR]: 0.29; 95% CI: 0.12 to 0.73; p = 0.005) and sudden death (HR: 0.46; 95% CI: 0.20 to 1.07; p = 0.065). There was no apparent impact of serelaxin treatment on HF deaths or non-CV deaths.
  
  
  CONCLUSIONS
  In the RELAX-AHF study, the effects of serelaxin on mortality were primarily driven by reduction in mortality from other CV causes and sudden death, without apparent impact on HF deaths. (Efficacy and Safety of Relaxin for the Treatment of Acute Heart Failure [RELAX-AHF]; NCT00520806).
authors.affiliation: Division of Cardiology, Duke University School of Medicine and Duke Heart Center, Durham, North Carolina. Electronic address: michael.felker@duke.edu.
authors.forename: G Michael
authors.initials: GM
authors.lastname: Felker
authors.affiliation: Division of Cardiology, University of California at San Francisco and San Francisco Veterans Affairs Medical Center, San Francisco, California.
authors.forename: John R
authors.initials: JR
authors.lastname: Teerlink
authors.affiliation: Division of Cardiology, Emory University, Atlanta, Georgia.
authors.forename: Javed
authors.initials: J
authors.lastname: Butler
authors.affiliation: Division of Cardiology, Duke University School of Medicine and Duke Heart Center, Durham, North Carolina.
authors.forename: Adrian F
authors.initials: AF
authors.lastname: Hernandez
authors.affiliation: Division of Cardiology, University of Florida, Jacksonville, Florida.
authors.forename: Alan B
authors.initials: AB
authors.lastname: Miller
authors.affiliation: Momentum Research Inc., Durham, North Carolina.
authors.forename: Gad
authors.initials: G
authors.lastname: Cotter
authors.affiliation: Momentum Research Inc., Durham, North Carolina.
authors.forename: Beth A
authors.initials: BA
authors.lastname: Davison
authors.affiliation: Department of Cardiology, Athens University Hospital, Attikon, Athens, Greece.
authors.forename: Gerasimos
authors.initials: G
authors.lastname: Filippatos
authors.affiliation: Division of Cardiology, University of California at San Diego, San Diego, California.
authors.forename: Barry H
authors.initials: BH
authors.lastname: Greenberg
authors.affiliation: Department of Cardiology, Medical University, Clinical Military Hospital, Wroclaw, Poland.
authors.forename: Piotr
authors.initials: P
authors.lastname: Ponikowski
authors.affiliation: Department of Cardiology, Ek, Groningen, the Netherlands.
authors.forename: Adriaan A
authors.initials: AA
authors.lastname: Voors
authors.affiliation: Novartis Pharmaceuticals Corp., East Hanover, New Jersey.
authors.forename: Tsushung A
authors.initials: TA
authors.lastname: Hua
authors.affiliation: Novartis Pharma AG, Basel, Switzerland.
authors.forename: Thomas M
authors.initials: TM
authors.lastname: Severin
authors.affiliation: Corthera, Inc., San Carlos, California.
authors.forename: Elaine
authors.initials: E
authors.lastname: Unemori
authors.affiliation: Cardiology, Department of Medical and Surgical Specialties, Radiological Sciences, and Public Health; University of Brescia, Brescia, Italy.
authors.forename: Marco
authors.initials: M
authors.lastname: Metra
mesh_terms: D000208:Acute Disease; D000368:Aged; D002423:Cause of Death / Q000639:trends; D016757:Death, Sudden, Cardiac / Q000453:epidemiology / Q000209:etiology / Q000517:prevention & control*; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D005260:Female; D005500:Follow-Up Studies; D006333:Heart Failure / Q000150:complications / Q000188:drug therapy* / Q000401:mortality; D006801:Humans; D007275:Injections, Intravenous; D008297:Male; D011446:Prospective Studies; D011994:Recombinant Proteins / Q000008:administration & dosage; D012065:Relaxin / Q000008:administration & dosage*; D015996:Survival Rate / Q000639:trends; D016896:Treatment Outcome
chemical_list: D011994:Recombinant Proteins; C577649:serelaxin protein, human; D012065:Relaxin
keywords: cause of death; heart failure; relaxin; sudden cardiac death