title: Effects of serelaxin in acute heart failure patients with renal impairment: results from RELAX-AHF.
abstract: BACKGROUND
  Serelaxin showed beneficial effects on clinical outcome and trajectories of renal markers in patients with acute heart failure. We aimed to study the interaction between renal function and the treatment effect of serelaxin.
  
  
  METHODS
  In the current post hoc analysis of the RELAX-AHF trial, we included all patients with available estimated glomerular filtration rate (eGFR) at baseline (n = 1132). Renal impairment was defined as an eGFR <60 ml/min/1.73 m(2) estimated by creatinine.
  
  
  RESULTS
  817 (72.2 %) patients had a baseline eGFR <60 ml/min/1.73 m(2). In placebo-treated patients, baseline renal impairment was related to a higher 180 day cardiovascular (HR 3.12, 95 % CI 1.33-7.30) and all-cause mortality (HR 2.81, 95 % CI 1.34-5.89). However, in serelaxin-treated patients, the risk of cardiovascular and all-cause mortality was less pronounced (HR 1.19, 95 % CI 0.54 -2.64; p for interaction = 0.106, and HR 1.15 95 % CI 0.56-2.34 respectively; p for interaction = 0.088). In patients with renal impairment, treatment with serelaxin resulted in a more pronounced all-cause mortality reduction (HR 0.53, 95 % CI 0.34-0.83), compared with patients without renal impairment (HR 1.30, 95 % CI 0.51-3.29).
  
  
  CONCLUSIONS
  Renal dysfunction was associated with higher cardiovascular and all-cause mortality in placebo-treated patients, but not in serelaxin-treated patients. The observed reduction in (cardiovascular) mortality in RELAX-AHF was more pronounced in patients with renal dysfunction. These observations need to be confirmed in the ongoing RELAX-AHF-2 trial.
authors.affiliation: Department of Cardiology, University Medical Center Groningen, Hanzeplein 1, 9713 GZ, Groningen, The Netherlands.
authors.forename: Licette C Y
authors.initials: LC
authors.lastname: Liu
authors.affiliation: Department of Cardiology, University Medical Center Groningen, Hanzeplein 1, 9713 GZ, Groningen, The Netherlands. a.a.voors@umcg.nl.
authors.forename: Adriaan A
authors.initials: AA
authors.lastname: Voors
authors.affiliation: San Francisco Veterans Affairs Medical Center, University of California, San Francisco, CA, USA.
authors.forename: John R
authors.initials: JR
authors.lastname: Teerlink
authors.affiliation: Momentum Research, Durham, NC, USA.
authors.forename: Gad
authors.initials: G
authors.lastname: Cotter
authors.affiliation: Momentum Research, Durham, NC, USA.
authors.forename: Beth A
authors.initials: BA
authors.lastname: Davison
authors.affiliation: Duke University School of Medicine, Duke Heart Center, Durham, NC, USA.
authors.forename: G Michael
authors.initials: GM
authors.lastname: Felker
authors.affiliation: School of Medicine, Attikon University Hospital, National and Kapodistrian University of Athens, Athens, Greece.
authors.forename: Gerasimos
authors.initials: G
authors.lastname: Filippatos
authors.affiliation: Columbia University Medical Center, New York, NY, USA.
authors.forename: Yakuan
authors.initials: Y
authors.lastname: Chen
authors.affiliation: University of California at San Diego, San Diego, CA, USA.
authors.forename: Barry H
authors.initials: BH
authors.lastname: Greenberg
authors.affiliation: Clinical Military Hospital, Medical University, Wroclaw, Poland.
authors.forename: Piotr
authors.initials: P
authors.lastname: Ponikowski
authors.affiliation: Indiana University School of Medicine, Indianapolis, IN, USA.
authors.forename: Peter S
authors.initials: PS
authors.lastname: Pang
authors.affiliation: Novartis Pharma, Basel, Switzerland.
authors.forename: Margaret F
authors.initials: MF
authors.lastname: Prescott
authors.affiliation: Novartis Pharma, Basel, Switzerland.
authors.forename: Tsushung A
authors.initials: TA
authors.lastname: Hua
authors.affiliation: Novartis Pharma, Basel, Switzerland.
authors.forename: Thomas M
authors.initials: TM
authors.lastname: Severin
authors.affiliation: University of Brescia, Brescia, Italy.
authors.forename: Marco
authors.initials: M
authors.lastname: Metra
mesh_terms: D000208:Acute Disease; D000368:Aged; D000369:Aged, 80 and over; D002317:Cardiovascular Agents / Q000009:adverse effects / Q000627:therapeutic use*; D005260:Female; D005919:Glomerular Filtration Rate / Q000187:drug effects*; D006333:Heart Failure / Q000150:complications / Q000188:drug therapy* / Q000401:mortality / Q000503:physiopathology; D006801:Humans; D053208:Kaplan-Meier Estimate; D007668:Kidney / Q000187:drug effects* / Q000503:physiopathology; D007674:Kidney Diseases / Q000150:complications / Q000188:drug therapy* / Q000401:mortality / Q000503:physiopathology; D008297:Male; D008875:Middle Aged; D016032:Randomized Controlled Trials as Topic; D011994:Recombinant Proteins / Q000009:adverse effects / Q000627:therapeutic use; D012065:Relaxin / Q000009:adverse effects / Q000627:therapeutic use*; D012189:Retrospective Studies; D013997:Time Factors; D016896:Treatment Outcome
chemical_list: D002317:Cardiovascular Agents; D011994:Recombinant Proteins; C577649:serelaxin protein, human; D012065:Relaxin
keywords: Acute heart failure; Number needed to treat; Renal function; Renal impairment; Serelaxin