Effects of serelaxin in patients with acute heart failure

Marco Metra, John R. Teerlink, Gad Cotter, Beth A. Davison, G. Michael Felker, Gerasimos Filippatos, Barry H. Greenberg, Peter S. Pang, Piotr Ponikowski, Adriaan A. Voors, Kirkwood F. Adams, Stefan D. Anker, Alexandra Arias-Mendoza, Patricio Avendaño, Fernando Bacal, Michael Böhm, Guillermo Bortman, John G.F. Cleland, Alain Cohen-Solal, Maria G. Crespo-LeiroMaria Dorobantu, Luis E. Echeverría, Roberto Ferrari, Sorel Goland, Eva Goncalvesová, Assen Goudev, Lars Køber, Juan Lema-Osores, Phillip D. Levy, Kenneth McDonald, Pravin Manga, Béla Merkely, Christian Mueller, Burkert Pieske, Jose Silva-Cardoso, Jindřich Špinar, Iain Squire, Janina Stępińska, Walter Van Mieghem, Dirk Von Lewinski, Gerhard Wikström, Mehmet B. Yilmaz, Nicole Hagner, Thomas Holbro, Tsushung A. Hua, Shalini V. Sabarwal, Thomas Severin, Peter Szecsödy, Claudio Gimpelewicz

Research output: Contribution to journalArticle

11 Citations (Scopus)

Abstract

BACKGROUND Serelaxin is a recombinant form of human relaxin-2, a vasodilator hormone that contributes to cardiovascular and renal adaptations during pregnancy. Previous studies have suggested that treatment with serelaxin may result in relief of symptoms and in better outcomes in patients with acute heart failure. METHODS In this multicenter, double-blind, placebo-controlled, event-driven trial, we enrolled patients who were hospitalized for acute heart failure and had dyspnea, vascular congestion on chest radiography, increased plasma concentrations of natriuretic peptides, mild-to-moderate renal insufficiency, and a systolic blood pressure of at least 125 mm Hg, and we randomly assigned them within 16 hours after presentation to receive either a 48-hour intravenous infusion of serelaxin (30 μg per kilogram of body weight per day) or placebo, in addition to standard care. The two primary end points were death from cardiovascular causes at 180 days and worsening heart failure at 5 days. RESULTS A total of 6545 patients were included in the intention-to-treat analysis. At day 180, death from cardiovascular causes had occurred in 285 of the 3274 patients (8.7%) in the serelaxin group and in 290 of the 3271 patients (8.9%) in the placebo group (hazard ratio, 0.98; 95% confidence interval [CI], 0.83 to 1.15; P=0.77). At day 5, worsening heart failure had occurred in 227 patients (6.9%) in the serelaxin group and in 252 (7.7%) in the placebo group (hazard ratio, 0.89; 95% CI, 0.75 to 1.07; P=0.19). There were no significant differences between the groups in the incidence of death from any cause at 180 days, the incidence of death from cardiovascular causes or rehospitalization for heart failure or renal failure at 180 days, or the length of the index hospital stay. The incidence of adverse events was similar in the two groups. CONCLUSIONS In this trial involving patients who were hospitalized for acute heart failure, an infusion of serelaxin did not result in a lower incidence of death from cardiovascular causes at 180 days or worsening heart failure at 5 days than placebo.

Original languageEnglish (US)
Pages (from-to)716-726
Number of pages11
JournalNew England Journal of Medicine
Volume381
Issue number8
DOIs
StatePublished - Aug 22 2019

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Heart Failure
Cause of Death
Placebos
Incidence
Renal Insufficiency
Confidence Intervals
Blood Pressure
Relaxin
Natriuretic Peptides
Intention to Treat Analysis
Vasodilator Agents
Intravenous Infusions
Radiography
Dyspnea
Blood Vessels
Length of Stay
Thorax
Body Weight
Hormones
Kidney

ASJC Scopus subject areas

  • Medicine(all)

Cite this

Metra, M., Teerlink, J. R., Cotter, G., Davison, B. A., Felker, G. M., Filippatos, G., ... Gimpelewicz, C. (2019). Effects of serelaxin in patients with acute heart failure. New England Journal of Medicine, 381(8), 716-726. https://doi.org/10.1056/NEJMoa1801291

Effects of serelaxin in patients with acute heart failure. / Metra, Marco; Teerlink, John R.; Cotter, Gad; Davison, Beth A.; Felker, G. Michael; Filippatos, Gerasimos; Greenberg, Barry H.; Pang, Peter S.; Ponikowski, Piotr; Voors, Adriaan A.; Adams, Kirkwood F.; Anker, Stefan D.; Arias-Mendoza, Alexandra; Avendaño, Patricio; Bacal, Fernando; Böhm, Michael; Bortman, Guillermo; Cleland, John G.F.; Cohen-Solal, Alain; Crespo-Leiro, Maria G.; Dorobantu, Maria; Echeverría, Luis E.; Ferrari, Roberto; Goland, Sorel; Goncalvesová, Eva; Goudev, Assen; Køber, Lars; Lema-Osores, Juan; Levy, Phillip D.; McDonald, Kenneth; Manga, Pravin; Merkely, Béla; Mueller, Christian; Pieske, Burkert; Silva-Cardoso, Jose; Špinar, Jindřich; Squire, Iain; Stępińska, Janina; Van Mieghem, Walter; Von Lewinski, Dirk; Wikström, Gerhard; Yilmaz, Mehmet B.; Hagner, Nicole; Holbro, Thomas; Hua, Tsushung A.; Sabarwal, Shalini V.; Severin, Thomas; Szecsödy, Peter; Gimpelewicz, Claudio.

In: New England Journal of Medicine, Vol. 381, No. 8, 22.08.2019, p. 716-726.

Research output: Contribution to journalArticle

Metra, M, Teerlink, JR, Cotter, G, Davison, BA, Felker, GM, Filippatos, G, Greenberg, BH, Pang, PS, Ponikowski, P, Voors, AA, Adams, KF, Anker, SD, Arias-Mendoza, A, Avendaño, P, Bacal, F, Böhm, M, Bortman, G, Cleland, JGF, Cohen-Solal, A, Crespo-Leiro, MG, Dorobantu, M, Echeverría, LE, Ferrari, R, Goland, S, Goncalvesová, E, Goudev, A, Køber, L, Lema-Osores, J, Levy, PD, McDonald, K, Manga, P, Merkely, B, Mueller, C, Pieske, B, Silva-Cardoso, J, Špinar, J, Squire, I, Stępińska, J, Van Mieghem, W, Von Lewinski, D, Wikström, G, Yilmaz, MB, Hagner, N, Holbro, T, Hua, TA, Sabarwal, SV, Severin, T, Szecsödy, P & Gimpelewicz, C 2019, 'Effects of serelaxin in patients with acute heart failure', New England Journal of Medicine, vol. 381, no. 8, pp. 716-726. https://doi.org/10.1056/NEJMoa1801291
Metra M, Teerlink JR, Cotter G, Davison BA, Felker GM, Filippatos G et al. Effects of serelaxin in patients with acute heart failure. New England Journal of Medicine. 2019 Aug 22;381(8):716-726. https://doi.org/10.1056/NEJMoa1801291
Metra, Marco ; Teerlink, John R. ; Cotter, Gad ; Davison, Beth A. ; Felker, G. Michael ; Filippatos, Gerasimos ; Greenberg, Barry H. ; Pang, Peter S. ; Ponikowski, Piotr ; Voors, Adriaan A. ; Adams, Kirkwood F. ; Anker, Stefan D. ; Arias-Mendoza, Alexandra ; Avendaño, Patricio ; Bacal, Fernando ; Böhm, Michael ; Bortman, Guillermo ; Cleland, John G.F. ; Cohen-Solal, Alain ; Crespo-Leiro, Maria G. ; Dorobantu, Maria ; Echeverría, Luis E. ; Ferrari, Roberto ; Goland, Sorel ; Goncalvesová, Eva ; Goudev, Assen ; Køber, Lars ; Lema-Osores, Juan ; Levy, Phillip D. ; McDonald, Kenneth ; Manga, Pravin ; Merkely, Béla ; Mueller, Christian ; Pieske, Burkert ; Silva-Cardoso, Jose ; Špinar, Jindřich ; Squire, Iain ; Stępińska, Janina ; Van Mieghem, Walter ; Von Lewinski, Dirk ; Wikström, Gerhard ; Yilmaz, Mehmet B. ; Hagner, Nicole ; Holbro, Thomas ; Hua, Tsushung A. ; Sabarwal, Shalini V. ; Severin, Thomas ; Szecsödy, Peter ; Gimpelewicz, Claudio. / Effects of serelaxin in patients with acute heart failure. In: New England Journal of Medicine. 2019 ; Vol. 381, No. 8. pp. 716-726.
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abstract = "BACKGROUND Serelaxin is a recombinant form of human relaxin-2, a vasodilator hormone that contributes to cardiovascular and renal adaptations during pregnancy. Previous studies have suggested that treatment with serelaxin may result in relief of symptoms and in better outcomes in patients with acute heart failure. METHODS In this multicenter, double-blind, placebo-controlled, event-driven trial, we enrolled patients who were hospitalized for acute heart failure and had dyspnea, vascular congestion on chest radiography, increased plasma concentrations of natriuretic peptides, mild-to-moderate renal insufficiency, and a systolic blood pressure of at least 125 mm Hg, and we randomly assigned them within 16 hours after presentation to receive either a 48-hour intravenous infusion of serelaxin (30 μg per kilogram of body weight per day) or placebo, in addition to standard care. The two primary end points were death from cardiovascular causes at 180 days and worsening heart failure at 5 days. RESULTS A total of 6545 patients were included in the intention-to-treat analysis. At day 180, death from cardiovascular causes had occurred in 285 of the 3274 patients (8.7{\%}) in the serelaxin group and in 290 of the 3271 patients (8.9{\%}) in the placebo group (hazard ratio, 0.98; 95{\%} confidence interval [CI], 0.83 to 1.15; P=0.77). At day 5, worsening heart failure had occurred in 227 patients (6.9{\%}) in the serelaxin group and in 252 (7.7{\%}) in the placebo group (hazard ratio, 0.89; 95{\%} CI, 0.75 to 1.07; P=0.19). There were no significant differences between the groups in the incidence of death from any cause at 180 days, the incidence of death from cardiovascular causes or rehospitalization for heart failure or renal failure at 180 days, or the length of the index hospital stay. The incidence of adverse events was similar in the two groups. CONCLUSIONS In this trial involving patients who were hospitalized for acute heart failure, an infusion of serelaxin did not result in a lower incidence of death from cardiovascular causes at 180 days or worsening heart failure at 5 days than placebo.",
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TY - JOUR

T1 - Effects of serelaxin in patients with acute heart failure

AU - Metra, Marco

AU - Teerlink, John R.

AU - Cotter, Gad

AU - Davison, Beth A.

AU - Felker, G. Michael

AU - Filippatos, Gerasimos

AU - Greenberg, Barry H.

AU - Pang, Peter S.

AU - Ponikowski, Piotr

AU - Voors, Adriaan A.

AU - Adams, Kirkwood F.

AU - Anker, Stefan D.

AU - Arias-Mendoza, Alexandra

AU - Avendaño, Patricio

AU - Bacal, Fernando

AU - Böhm, Michael

AU - Bortman, Guillermo

AU - Cleland, John G.F.

AU - Cohen-Solal, Alain

AU - Crespo-Leiro, Maria G.

AU - Dorobantu, Maria

AU - Echeverría, Luis E.

AU - Ferrari, Roberto

AU - Goland, Sorel

AU - Goncalvesová, Eva

AU - Goudev, Assen

AU - Køber, Lars

AU - Lema-Osores, Juan

AU - Levy, Phillip D.

AU - McDonald, Kenneth

AU - Manga, Pravin

AU - Merkely, Béla

AU - Mueller, Christian

AU - Pieske, Burkert

AU - Silva-Cardoso, Jose

AU - Špinar, Jindřich

AU - Squire, Iain

AU - Stępińska, Janina

AU - Van Mieghem, Walter

AU - Von Lewinski, Dirk

AU - Wikström, Gerhard

AU - Yilmaz, Mehmet B.

AU - Hagner, Nicole

AU - Holbro, Thomas

AU - Hua, Tsushung A.

AU - Sabarwal, Shalini V.

AU - Severin, Thomas

AU - Szecsödy, Peter

AU - Gimpelewicz, Claudio

PY - 2019/8/22

Y1 - 2019/8/22

N2 - BACKGROUND Serelaxin is a recombinant form of human relaxin-2, a vasodilator hormone that contributes to cardiovascular and renal adaptations during pregnancy. Previous studies have suggested that treatment with serelaxin may result in relief of symptoms and in better outcomes in patients with acute heart failure. METHODS In this multicenter, double-blind, placebo-controlled, event-driven trial, we enrolled patients who were hospitalized for acute heart failure and had dyspnea, vascular congestion on chest radiography, increased plasma concentrations of natriuretic peptides, mild-to-moderate renal insufficiency, and a systolic blood pressure of at least 125 mm Hg, and we randomly assigned them within 16 hours after presentation to receive either a 48-hour intravenous infusion of serelaxin (30 μg per kilogram of body weight per day) or placebo, in addition to standard care. The two primary end points were death from cardiovascular causes at 180 days and worsening heart failure at 5 days. RESULTS A total of 6545 patients were included in the intention-to-treat analysis. At day 180, death from cardiovascular causes had occurred in 285 of the 3274 patients (8.7%) in the serelaxin group and in 290 of the 3271 patients (8.9%) in the placebo group (hazard ratio, 0.98; 95% confidence interval [CI], 0.83 to 1.15; P=0.77). At day 5, worsening heart failure had occurred in 227 patients (6.9%) in the serelaxin group and in 252 (7.7%) in the placebo group (hazard ratio, 0.89; 95% CI, 0.75 to 1.07; P=0.19). There were no significant differences between the groups in the incidence of death from any cause at 180 days, the incidence of death from cardiovascular causes or rehospitalization for heart failure or renal failure at 180 days, or the length of the index hospital stay. The incidence of adverse events was similar in the two groups. CONCLUSIONS In this trial involving patients who were hospitalized for acute heart failure, an infusion of serelaxin did not result in a lower incidence of death from cardiovascular causes at 180 days or worsening heart failure at 5 days than placebo.

AB - BACKGROUND Serelaxin is a recombinant form of human relaxin-2, a vasodilator hormone that contributes to cardiovascular and renal adaptations during pregnancy. Previous studies have suggested that treatment with serelaxin may result in relief of symptoms and in better outcomes in patients with acute heart failure. METHODS In this multicenter, double-blind, placebo-controlled, event-driven trial, we enrolled patients who were hospitalized for acute heart failure and had dyspnea, vascular congestion on chest radiography, increased plasma concentrations of natriuretic peptides, mild-to-moderate renal insufficiency, and a systolic blood pressure of at least 125 mm Hg, and we randomly assigned them within 16 hours after presentation to receive either a 48-hour intravenous infusion of serelaxin (30 μg per kilogram of body weight per day) or placebo, in addition to standard care. The two primary end points were death from cardiovascular causes at 180 days and worsening heart failure at 5 days. RESULTS A total of 6545 patients were included in the intention-to-treat analysis. At day 180, death from cardiovascular causes had occurred in 285 of the 3274 patients (8.7%) in the serelaxin group and in 290 of the 3271 patients (8.9%) in the placebo group (hazard ratio, 0.98; 95% confidence interval [CI], 0.83 to 1.15; P=0.77). At day 5, worsening heart failure had occurred in 227 patients (6.9%) in the serelaxin group and in 252 (7.7%) in the placebo group (hazard ratio, 0.89; 95% CI, 0.75 to 1.07; P=0.19). There were no significant differences between the groups in the incidence of death from any cause at 180 days, the incidence of death from cardiovascular causes or rehospitalization for heart failure or renal failure at 180 days, or the length of the index hospital stay. The incidence of adverse events was similar in the two groups. CONCLUSIONS In this trial involving patients who were hospitalized for acute heart failure, an infusion of serelaxin did not result in a lower incidence of death from cardiovascular causes at 180 days or worsening heart failure at 5 days than placebo.

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