Effect of IV Iron on Exercise Capacity in Patients With Chronic HF and Iron Deficiency

Study Questions:

The purpose of the EFFECT-HF (Effect of Ferric Carboxymaltose on Exercise Capacity in Patients With Iron Deficiency and Chronic Heart Failure) trial is to examine the effect of treatment with intravenous (IV) ferric carboxymaltose compared with standard of care (including oral iron supplementation), on exercise capacity in patients with symptomatic chronic heart failure (HF) and iron deficiency.

Methods:

The EFFECT-HF trial was a prospective randomized, controlled, multicenter, open-label trial with blinded end-point evaluation that examined the effect of treatment with IV ferric carboxymaltose compared with standard of care on exercise capacity in patients with symptomatic chronic HF and iron deficiency. The primary endpoint was the change in peak VO2 from baseline to 24 weeks. Secondary endpoints included the effect of ferric carboxymaltose on hematinic indices, B-type natriuretic peptide and N-terminal pro-B-type natriuretic peptide, New York Heart Association functional class, and patient global assessment.

Results:

The study population (n = 172) consisted of 86 patients in the intervention group and control group from 28 sites in 8 countries. There were no differences between study and control group on peak VO2 (p = 0.93). Patients with anemia did not benefit more than patients without anemia (p for interaction = 0.758), and in patients treated with ferric carboxymaltose, there was no association between the change in hemoglobin and the change in peak VO2 (for ferric carboxymaltose, r = 0.0758, p = 0.51). Patients in the ferric carboxymaltose group had improved New York Heart Association classification compared with the control group (p < 0.05). Patient global assessment was favorably affected in the ferric carboxymaltose group at 12 and 24 weeks post-treatment (p < 0.05). B-type natriuretic peptide and N-terminal pro-B-type natriuretic peptide were similar at baseline in both groups, but there was no statistical change in values between the two groups. No hypersensitivity reactions to ferric carboxymaltose or hypophosphatemia were reported.

Conclusions:

Iron deficiency is a serious comorbidity in patients with HF that is associated with an increase in morbidity and mortality. In this study, ferric carboxymaltose improved functional status and feeling of well-being. Even though this study did not show an effect on Peak VO2, the authors explained that this may be due to the dependence of the finding on the imputation method. Previous studies have shown an improvement in 6-minute walk tests in patients receiving ferric carboxymaltose, which may have been a beneficial measurement to determine the effect of ferric carboxymaltose in this study.

Perspective:

Treating iron deficiency is important in patients with HF, but using oral iron supplementation as first line therapy can have inconsistent results due to poor intestinal absorption. The use of ferric carboxymaltose should be considered as a treatment option for patients with iron deficiency when there is no improvement in iron stores with oral supplementation. Currently, there are two large studies in progress, AFFIRM-AHF (Study to Compare Ferric Carboxymaltose With Placebo in Patients With Acute Heart Failure and Iron Deficiency) and FAIR-HF (Ferinject® Assessment in Patients With Iron Deficiency and Chronic Heart Failure), that are looking at the effect of ferric carboxymaltose on HF outcomes to support the use of IV supplementation.

Keywords: Hematinics, Iron, Heart Failure, Natriuretic Peptide, Brain, Comorbidity, Exercise Tolerance, Ferric Compounds, Hemoglobins, Intestinal Absorption


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