Iron Deficiency and Administration of Ferric Carboxymaltose in Patients with Heart Failure

Methodology and Study Course

AFFIRM-AHF was a multicenter randomized double-blind placebo-controlled study conducted in Europe, South America, and Singapore. All enrolled patients were over 18 years old and were hospitalized for symptoms of acute heart failure requiring intravenous administration of at least 40 mg of furosemide. These patients had a reduced left ventricle ejection fraction (LVEF) below 50% (ascertained no longer than 12 months before the start of the study). All patients also suffered from iron deficiency defined as a serum ferritin level < 100 μg/l or ferritin levels 100–299 μg/l with transferrin saturation < 20%.

Before discharge from hospitalization, patients were randomly divided into two groups (1:1). The first group received ferric carboxymaltose for 24 weeks, while the second group received a placebo. The dosing was based on the depth of the iron deficiency. An initial dose was administered shortly before discharge, followed by another dose 6 weeks later. The next two doses (at the 12th and 24th week of follow-up) were given only to patients with persistent iron deficiency and hemoglobin levels between 80-150 g/l.

The primary measured outcome was the occurrence of a composite parameter including hospitalization for symptoms of acute heart failure and overall cardiovascular mortality over a period of 52 weeks after the start of the follow-up. Additionally, the risk of cardiovascular mortality, cardiovascular hospitalizations, and time to first heart failure hospitalization were individually monitored.

Results

Out of a total of 1,525 patients, 1,132 were included in the study. Of these, 567 participants were assigned to the ferric carboxymaltose group and 565 to the placebo group. Treatment was initiated in 1,110 patients, and at least one follow-up outcome was obtained for 1,108.

In the FCM treatment group, 370 occurrences of the composite parameter including heart failure hospitalization and cardiovascular mortality were recorded, while 451 occurrences were observed in the placebo group (relative risk [RR] 0.80; 95% confidence interval [CI] 0.64–1.00; p = 0.05). No difference in cardiovascular mortality incidence was noted between the two groups (77 [14%] cases in the FCM group and 78 [14%] in the placebo group; hazard ratio [HR] 0.96; 95% CI 0.70–1.32; p = 0.81). 217 patients treated with FCM were hospitalized for symptoms of acute heart failure, while 294 patients in the placebo group were hospitalized (RR 0.74; 95% CI 0.58–0.94; p = 0.013).

The total dose of FCM administered during the study averaged 1,352 mg. Laboratory values showed an increase in hemoglobin levels by 8 g/l in the FCM group and by 3 g/l in the placebo group. The FCM group also experienced a significant rise in serum ferritin levels and transferrin saturation.

Conclusion and Discussion

The study results indicate that in patients with iron deficiency and reduced LVEF (< 50%) stabilized after an episode of acute heart failure, administration of ferric carboxymaltose is safe, well-tolerated, and significantly (by approximately 26%) reduces the risk of subsequent hospitalizations for acute heart failure symptoms. No clear difference in cardiovascular mortality was observed compared to patients receiving a placebo.

Iron, as an essential micronutrient, plays a role in the energy metabolism of hematopoietic and other tissue cells. Iron deficiency in patients with acute heart failure is primarily characterized by unmet needs of this element in peripheral tissue cells, leading to disrupted metabolism and energy homeostasis of the organism. The use of FCM in at-risk individuals, regardless of the presence of anemia, has shown a positive effect both in compensating for iron deficiency and in reducing the number of hospitalizations.

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Source: Ponikowski P., Kirwan B.-A., Anker S. D. et al. Ferric carboxymaltose for iron deficiency at discharge after acute heart failure: a multicentre, double-blind, randomised, controlled trial. Lancet 2020; 396 (10266): 1895–1904, doi: 10.1016/S0140-6736(20)32339-4.