Ferric Carboxymaltose in Heart Failure with Iron Deficiency

N Engl J Med. 2023 Sep 14;389(11):975-986. doi: 10.1056/NEJMoa2304968. Epub 2023 Aug 26.


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.).

Publication types

  • Randomized Controlled Trial

MeSH terms

  • Administration, Intravenous
  • Ambulatory Care
  • Double-Blind Method
  • Ferric Compounds* / administration & dosage
  • Ferric Compounds* / adverse effects
  • Ferric Compounds* / therapeutic use
  • Heart Failure* / complications
  • Heart Failure* / drug therapy
  • Heart Failure* / physiopathology
  • Humans
  • Iron Deficiencies* / complications
  • Iron Deficiencies* / drug therapy
  • Quality of Life
  • Stroke Volume
  • Ventricular Function, Left


  • ferric carboxymaltose
  • Ferric Compounds

Associated data

  • ClinicalTrials.gov/NCT03037931