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.
RCT Entities:
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.
Authors: Veli-Pekka Harjola; Wilfried Mullens; Marek Banaszewski; Johann Bauersachs; Hans-Peter Brunner-La Rocca; Ovidiu Chioncel; Sean P Collins; Wolfram Doehner; Gerasimos S Filippatos; Andreas J Flammer; Valentin Fuhrmann; Mitja Lainscak; Johan Lassus; Matthieu Legrand; Josep Masip; Christian Mueller; Zoltán Papp; John Parissis; Elke Platz; Alain Rudiger; Frank Ruschitzka; Andreas Schäfer; Petar M Seferovic; Hadi Skouri; Mehmet Birhan Yilmaz; Alexandre Mebazaa Journal: Eur J Heart Fail Date: 2017-05-30 Impact factor: 15.534
Authors: Horng H Chen; Omar F AbouEzzeddine; Kevin J Anstrom; Michael M Givertz; Bradley A Bart; G Michael Felker; Adrian F Hernandez; Kerry L Lee; Eugene Braunwald; Margaret M Redfield Journal: Circ Heart Fail Date: 2013-09-01 Impact factor: 8.790
Authors: Robert J Mentz; Gary Michael Felker; Tariq Ahmad; William Frank Peacock; Bertram Pitt; Mona Fiuzat; Aldo P Maggioni; Mihai Gheorghiade; Yuki Ando; Stuart J Pocock; Faiez Zannad; Christopher M O'Connor Journal: Am Heart J Date: 2013-09-13 Impact factor: 4.749
Authors: Joerg C Schefold; Gerasimos Filippatos; Gerd Hasenfuss; Stefan D Anker; Stephan von Haehling Journal: Nat Rev Nephrol Date: 2016-08-30 Impact factor: 28.314
Authors: Stephen J Greene; Robert J Mentz; Mona Fiuzat; Javed Butler; Scott D Solomon; Andrew P Ambrosy; Cyrus Mehta; John R Teerlink; Faiez Zannad; Christopher M O'Connor Journal: Circulation Date: 2018-09-04 Impact factor: 29.690