Effect of Serelaxin on Cardiac, Renal, and Hepatic Biomarkers in the Relaxin in Acute Heart Failure (RELAX-AHF) Development Program: Correlation With Outcomes

J Am Coll Cardiol. 2013 Jan 15;61(2):196-206. doi: 10.1016/j.jacc.2012.11.005.

Abstract

Objectives: 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.

Publication types

  • Clinical Trial, Phase II
  • Clinical Trial, Phase III
  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acute Disease
  • Alanine Transaminase / blood
  • Aspartate Aminotransferases / blood
  • Biomarkers / blood*
  • Creatinine / blood
  • Cystatin C / blood
  • Double-Blind Method
  • Heart Failure / blood
  • Heart Failure / drug therapy*
  • Heart Failure / mortality
  • Hospitalization
  • Humans
  • Kidney / drug effects*
  • Kidney / metabolism
  • Liver / drug effects*
  • Liver / metabolism
  • Natriuretic Peptide, Brain / blood
  • Peptide Fragments / blood
  • Recombinant Proteins / administration & dosage
  • Recombinant Proteins / pharmacology
  • Relaxin / administration & dosage
  • Relaxin / pharmacology*
  • Survival Rate
  • Treatment Outcome
  • Troponin T / blood

Substances

  • Biomarkers
  • Cystatin C
  • Peptide Fragments
  • Recombinant Proteins
  • Troponin T
  • pro-brain natriuretic peptide (1-76)
  • serelaxin protein, human
  • Natriuretic Peptide, Brain
  • Relaxin
  • Creatinine
  • Aspartate Aminotransferases
  • Alanine Transaminase