Ferric Carboxymaltose in Heart Failure with Iron Deficiency.
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:
14 Sep 2023
14 Sep 2023
Historique:
medline:
15
9
2023
pubmed:
27
8
2023
entrez:
26
8
2023
Statut:
ppublish
Résumé
Ferric carboxymaltose therapy reduces symptoms and improves quality of life in patients who have heart failure with a reduced ejection fraction and iron deficiency. Additional evidence about the effects of ferric carboxymaltose on clinical events is needed. In this double-blind, randomized trial, we assigned ambulatory patients with heart failure, a left ventricular ejection fraction of 40% or less, and iron deficiency, in a 1:1 ratio, to receive intravenous ferric carboxymaltose or placebo, in addition to standard therapy for heart failure. Ferric carboxymaltose or placebo was given every 6 months as needed on the basis of iron indexes and hemoglobin levels. The primary outcome was a hierarchical composite of death within 12 months after randomization, hospitalizations for heart failure within 12 months after randomization, or change from baseline to 6 months in the 6-minute walk distance. The significance level was set at 0.01. We enrolled 3065 patients, of whom 1532 were randomly assigned to the ferric carboxymaltose group and 1533 to the placebo group. Death by month 12 occurred in 131 patients (8.6%) in the ferric carboxymaltose group and 158 (10.3%) in the placebo group; a total of 297 and 332 hospitalizations for heart failure, respectively, occurred by month 12; and the mean (±SD) change from baseline to 6 months in the 6-minute walk distance was 8±60 and 4±59 m, respectively (Wilcoxon-Mann-Whitney P = 0.02; unmatched win ratio, 1.10; 99% confidence interval, 0.99 to 1.23). Repeated dosing of ferric carboxymaltose appeared to be safe with an acceptable adverse-event profile in the majority of patients. The number of patients with serious adverse events occurring during the treatment period was similar in the two groups (413 patients [27.0%] in the ferric carboxymaltose group and 401 [26.2%] in the placebo group). Among ambulatory patients who had heart failure with a reduced ejection fraction and iron deficiency, there was no apparent difference between ferric carboxymaltose and placebo with respect to the hierarchical composite of death, hospitalizations for heart failure, or 6-minute walk distance. (Funded by American Regent, a Daiichi Sankyo Group company; HEART-FID ClinicalTrials.gov number, NCT03037931.).
Sections du résumé
BACKGROUND
BACKGROUND
Ferric carboxymaltose therapy reduces symptoms and improves quality of life in patients who have heart failure with a reduced ejection fraction and iron deficiency. Additional evidence about the effects of ferric carboxymaltose on clinical events is needed.
METHODS
METHODS
In this double-blind, randomized trial, we assigned ambulatory patients with heart failure, a left ventricular ejection fraction of 40% or less, and iron deficiency, in a 1:1 ratio, to receive intravenous ferric carboxymaltose or placebo, in addition to standard therapy for heart failure. Ferric carboxymaltose or placebo was given every 6 months as needed on the basis of iron indexes and hemoglobin levels. The primary outcome was a hierarchical composite of death within 12 months after randomization, hospitalizations for heart failure within 12 months after randomization, or change from baseline to 6 months in the 6-minute walk distance. The significance level was set at 0.01.
RESULTS
RESULTS
We enrolled 3065 patients, of whom 1532 were randomly assigned to the ferric carboxymaltose group and 1533 to the placebo group. Death by month 12 occurred in 131 patients (8.6%) in the ferric carboxymaltose group and 158 (10.3%) in the placebo group; a total of 297 and 332 hospitalizations for heart failure, respectively, occurred by month 12; and the mean (±SD) change from baseline to 6 months in the 6-minute walk distance was 8±60 and 4±59 m, respectively (Wilcoxon-Mann-Whitney P = 0.02; unmatched win ratio, 1.10; 99% confidence interval, 0.99 to 1.23). Repeated dosing of ferric carboxymaltose appeared to be safe with an acceptable adverse-event profile in the majority of patients. The number of patients with serious adverse events occurring during the treatment period was similar in the two groups (413 patients [27.0%] in the ferric carboxymaltose group and 401 [26.2%] in the placebo group).
CONCLUSIONS
CONCLUSIONS
Among ambulatory patients who had heart failure with a reduced ejection fraction and iron deficiency, there was no apparent difference between ferric carboxymaltose and placebo with respect to the hierarchical composite of death, hospitalizations for heart failure, or 6-minute walk distance. (Funded by American Regent, a Daiichi Sankyo Group company; HEART-FID ClinicalTrials.gov number, NCT03037931.).
Identifiants
pubmed: 37632463
doi: 10.1056/NEJMoa2304968
doi:
Substances chimiques
ferric carboxymaltose
6897GXD6OE
Ferric Compounds
0
Banques de données
ClinicalTrials.gov
['NCT03037931']
Types de publication
Randomized Controlled Trial
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
975-986Investigateurs
Carmine De Pasquale
(C)
Michael Stokes
(M)
Isuru Ranasinghe
(I)
Alicia Chan
(A)
Matthew Best
(M)
Kaitlyn Lam
(K)
John Atherton
(J)
Yee Weng Wong
(YW)
Scott McKenzie
(S)
Steven Sutcliffe
(S)
David Cross
(D)
John Amerena
(J)
Hendrik Zimmet
(H)
Matthew Marrinan
(M)
David Colquhoun
(D)
Peter MacDonald
(P)
Laurie Howes
(L)
Gayathri Kumarasinghe
(G)
John French
(J)
Nathan Dwyer
(N)
Aaron Sverdlov
(A)
Valentina Grigorova
(V)
Katerina Vitliyanova
(K)
Ivan Martinov
(I)
Maria Tzekova
(M)
Miroslav Stoyanov
(M)
Bojidar Dimov
(B)
Ivan Efremov
(I)
Ivaylo Vasilev
(I)
Georgi Todorov
(G)
Valentina Mincheva-Kabakchieva
(V)
Haralambi Benov
(H)
Yordan Dzhumean
(Y)
Savka Vaklyova
(S)
Tanya Petkova
(T)
Sebastien Bergeron
(S)
Sudip Datta
(S)
Brian Clarke
(B)
Robert Miller
(R)
Danielle Dion
(D)
Ryan Davey
(R)
Justin Ezekowitz
(J)
Nadia Giannetti
(N)
Mikael Hanninen
(M)
Amit Khosla
(A)
Dante Manyari
(D)
Gordon Moe
(G)
Eileen O'Meara
(E)
Amritanshu Pandey
(A)
John Parker
(J)
Yves Pesant
(Y)
Miroslaw Rajda
(M)
Richard Vandegriend
(R)
Denis Saulnier
(D)
Ying Tung Sia
(YT)
Bruce Sussex
(B)
Elizabeth Swiggum
(E)
Mustafa Toma
(M)
Alexander Zhai
(A)
Saul Vizel
(S)
Marc Benoit
(M)
Ronald Bourgeois
(R)
Martin Wiendl
(M)
Ondrej Toman
(O)
Jan Belohlavek
(J)
Vojtech Melenovsky
(V)
Anu Hedman
(A)
George Khabeishvili
(G)
Tamaz Shaburishvili
(T)
Irakli Khintibidze
(I)
Levan Kurashvili
(L)
Giorgi Nikolaishvili
(G)
Rusudan Agladze
(R)
Teona Gvinianidze
(T)
Zurab Klimiashvili
(Z)
Vakhtang Chumburidze
(V)
Nodar Emukhvari
(N)
Andrea Hornyik
(A)
Geza Lupkovics
(G)
Annamaria Piros
(A)
Bela Herczeg
(B)
Zeno Ajtay
(Z)
Zoltan Csanadi
(Z)
Andras Nagy
(A)
Orsolya Balogh
(O)
Bela Merkely
(B)
Iveta Sime
(I)
Natalja Kakurina
(N)
Dalia Jarasuniene
(D)
Jelena Celutkiene
(J)
Gintare Sakalyte
(G)
Jocelyne Benatar
(J)
Hamish Hart
(H)
Patrick Gladding
(P)
Mayanna Lund
(M)
John Baker
(J)
Ian Ternouth
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Andrew Corin
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Richard Luke
(R)
Timothy O'Meeghan
(T)
Scott Harding
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Alyssa Kirby
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Tammy Pegg
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Richard Troughton
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Piotr Abramczyk
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Marcin Ogorek
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Grzegorz Skonieczny
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