Effects of Serelaxin in Patients with Acute Heart Failure.
Acute Disease
Aged
Blood Pressure
/ drug effects
Cardiovascular Diseases
/ mortality
Disease Progression
Double-Blind Method
Female
Heart Failure
/ drug therapy
Hospitalization
Humans
Incidence
Infusions, Intravenous
Male
Recombinant Proteins
/ adverse effects
Relaxin
/ adverse effects
Treatment Failure
Vasodilator Agents
/ adverse effects
Journal
The New England journal of medicine
ISSN: 1533-4406
Titre abrégé: N Engl J Med
Pays: United States
ID NLM: 0255562
Informations de publication
Date de publication:
22 08 2019
22 08 2019
Historique:
entrez:
22
8
2019
pubmed:
23
8
2019
medline:
29
8
2019
Statut:
ppublish
Résumé
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. 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. 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. 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. (Funded by Novartis Pharma; RELAX-AHF-2 ClinicalTrials.gov number, NCT01870778.).
Sections du résumé
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. (Funded by Novartis Pharma; RELAX-AHF-2 ClinicalTrials.gov number, NCT01870778.).
Identifiants
pubmed: 31433919
doi: 10.1056/NEJMoa1801291
doi:
Substances chimiques
Recombinant Proteins
0
Vasodilator Agents
0
serelaxin protein, human
0
Relaxin
9002-69-1
Banques de données
ClinicalTrials.gov
['NCT01870778']
Types de publication
Journal Article
Multicenter Study
Randomized Controlled Trial
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
716-726Investigateurs
Horacio Avaca
(H)
Guillermo Moises Azize
(GM)
Mario Alberto Berli
(MA)
Alberto Caccavo
(A)
Diego Carroza
(D)
Luis Cartasegna
(L)
German Cestari
(G)
Santorio Guemes
(S)
Fabian Diez
(F)
Mirta Diez
(M)
Alberto Fernandez
(A)
Matias Fosco
(M)
Daniela Garcia Brasca
(D)
Patricia Gitelman
(P)
Rodolfo Ahuad Guerrero
(RA)
Miguel Hominal
(M)
Horacio Jure
(H)
Gustavo Bustamante Labarta
(G)
Ricardo Leon de la Fuente
(RL)
Hugo Luquez
(H)
Lilia Lobo Marquez
(LL)
Sebastian Nani
(S)
Eduardo Perna
(E)
Carlos Poy
(C)
Aldo Prado
(A)
Hugo Ramos
(H)
Rodolfo Sarjanovich
(R)
Lilia Schiavi
(L)
Pablo Severino
(P)
Carlos Sosa
(C)
Oscar Vogelmann
(O)
Gerardo Zapata
(G)
Daniel Zivano
(D)
John Amerena
(J)
John Atherton
(J)
Carmine DePasquale
(C)
Nigel Jepson
(N)
Henry Krum
(H)
Kaitlyn Lam
(K)
JoDee Lattimore
(J)
Andrew Sindone
(A)
Geoff Tofler
(G)
Joahnn Auer
(J)
Diana Bonderman
(D)
Bernd Eber
(B)
Christian Ebner
(C)
Uta Hoppe
(U)
Gerhard Polzl
(G)
Anna Rab
(A)
Peter Siostrzonek
(P)
An-Kristen Ascoop
(AK)
Patrick Carlier
(P)
Ignace Demeyer
(I)
Walter Droogne
(W)
Christian Melot
(C)
Wilfried Mullens
(W)
Oliver Van Caenegem
(OV)
Denilson Albuquerque
(D)
Luis Beck
(L)
Almir Sergio Ferraz
(AS)
Lilia Nigro Maia
(LN)
Euler Manenti
(E)
Salvador Rassi
(S)
Paulo R Rossi
(PR)
Marcus Vinicius Simoes
(MV)
Nikolay Atanasov
(N)
Bojidar Dimov
(B)
Petar Lazov
(P)
Maria Milanova
(M)
Dimitar Raev
(D)
Nina Shehova-Iankova
(N)
Snezhanka Tisheva-Gospodinova
(S)
Georgi Todorov
(G)
Maria Tzekova
(M)
Yoto Yotov
(Y)
Jonathan Howlett
(J)
Claude Lauzon
(C)
Guy Proulx
(G)
Mauricio Fernandez
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(JL)
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(AJ)
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Lubomir Buncek
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Pavel Cervinka
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