Ferric Carboxymaltose in Heart Failure with Iron Deficiency

From the Division of Cardiology, Department of Medicine (R.J.M., J.H., A.F.H.), and the Department of Biostatistics and Bioinformatics (F.W.R.), Duke University School of Medicine, and Duke Clinical Research Institute (R.J.M., J.G., F.W.R., L.S., J.H., A.F.H.) - both in Durham, NC; Baylor Scott and White Research Institute, Dallas (J.B.); the Department of Medicine, University of Mississippi, Jackson (J.B.); Flinders Medical Centre, Flinders University, Adelaide, SA (C.G.D.P.), and the Department of Cardiology, Prince Charles Hospital and Faculty of Medicine, University of Queensland, Brisbane (Y.W.W.) - both in Australia; Canadian VIGOUR Centre, University of Alberta, Edmonton (J.A.E.), and Montreal Heart Institute and Université de Montréal, Montreal (E.O.) - both in Canada; the Cardiology Division and Cardiovascular Research Center, Massachusetts General Hospital, Boston (G.D.L.); the Center for Heart Diseases, University Hospital, Wroclaw Medical University, Wroclaw, Poland (P.P.); Christchurch Heart Institute, University of Otago, Christchurch, New Zealand (R.W.T.); the Department of Cardiovascular Medicine, Mayo Clinic, Rochester, MN (Y.W.W.); and American Regent, Shirley, NY (R.A., N.B.).

The New England journal of medicine. 2023
PICO Summary

Population

Patients with heart failure and iron deficiency (n= 3,065).

Intervention

Intravenous ferric carboxymaltose group (n= 1,532).

Comparison

Placebo (n= 1,533).

Outcome

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 (unmatched win ratio, 1.10; 99% confidence interval [0.99, 1.23]). 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.
Abstract
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 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 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 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.).
Study details
Language : eng
Credits : Bibliographic data from MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine