Effect of serelaxin on cardiac, renal, and hepatic biomarkers in the relaxin in acute heart failure (RELAX-AHF) development program: Correlation with outcomes

Marco Metra, Gad Cotter, Beth A. Davison, G. Michael Felker, Gerasimos Filippatos, Barry H. Greenberg, Piotr Ponikowski, Elaine Unemori, Adriaan A. Voors, Kirkwood F. Adams, Maria I. Dorobantu, Liliana Grinfeld, Guillaume Jondeau, Alon Marmor, Josep Masip, Peter S. Pang, Karl Werdan, Margaret F. Prescott, Christopher Edwards, Sam L. TeichmanAngelo Trapani, Christopher A. Bush, Rajnish Saini, Christoph Schumacher, Thomas Severin, John R. Teerlink

Research output: Contribution to journalArticle

308 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)196-206
Number of pages11
JournalJournal of the American College of Cardiology
Volume61
Issue number2
DOIs
StatePublished - Jan 15 2013

Keywords

  • RELAX-AHF
  • congestion
  • heart failure
  • organ protection
  • serelaxin

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine

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    Metra, M., Cotter, G., Davison, B. A., Felker, G. M., Filippatos, G., Greenberg, B. H., Ponikowski, P., Unemori, E., Voors, A. A., Adams, K. F., Dorobantu, M. I., Grinfeld, L., Jondeau, G., Marmor, A., Masip, J., Pang, P. S., Werdan, K., Prescott, M. F., Edwards, C., ... Teerlink, J. R. (2013). Effect of serelaxin on cardiac, renal, and hepatic biomarkers in the relaxin in acute heart failure (RELAX-AHF) development program: Correlation with outcomes. Journal of the American College of Cardiology, 61(2), 196-206. https://doi.org/10.1016/j.jacc.2012.11.005