Oral Iron Supplementation Does Not Improve Functional Capacity in Chronic HF

Iron deficiency is present in approximately 50% of patients with chronic heart failure (HF), and HF complicated with iron deficiency is associated with impaired functional capacity, poor quality of life, and increased mortality. Although these factors point to iron deficiency as a therapeutic target in HF, the findings of a recent study show that oral iron supplementation may not improve functional capacity in patients with HF and reduced ejection fraction. 

On behalf of the National Heart, Lung, and Blood Institute's Heart Failure Clinical Research Network, Gregory D. Lewis, MD, of Massachusetts General Hospital in Boston, presented the results of the study at the Scientific Sessions of the American Heart Association held November 12 to 16, 2016, in New Orleans, LA. Duke investigators involved in the study included Kevin J. Anstrom, PhD, Steven E. McNulty, MS, and Adrian F. Hernandez, MD.

The findings of other studies have shown that intravenous iron increased 6-minute walk distance and quality of life and decreased HF-related hospitalizations in patients with HF and reduced ejection fraction.

However, the administration of intravenous iron poses logistical challenges and is expensive, said Lewis. He added that oral iron is safe and readily available, but its efficacy in HF is unknown. Patient characteristics that influence responsiveness to oral iron in HF also remain undefined.

Lewis and his co-investigators sought to test the hypothesis that oral iron polysaccharide is superior to oral placebo in improving exercise capacity (peak oxygen consumption) in patients who have HF, reduced ejection fraction, and iron deficiency at 16 weeks.

The study included 225 patients with New York Heart Association functional classification II to IV HF symptoms and left ventricular ejection fraction of 40% or less. Patients had to have a serum ferritin level of 15 to 100 ng/mL or a serum ferritin level of 100 to 299 ng/mL with transferrin saturation of less than 20%. All patients had stable chronic HF and were receiving evidence-based medical therapy.

The study participants were randomly assigned to receive twice-daily oral iron polysaccharide 150 mg (n = 111) or placebo (n = 114).

The primary end point was change in peak oxygen consumption at 16 weeks, and secondary end points included change in 6-minute walk distance, oxygen kinetics, ventilator efficiency, change in N-terminal pro-brain natriuretic peptide level, and change in quality-of-life score on the Kansas City Cardiomyopathy Questionnaire.

No significant differences were observed in the change in peak oxygen consumption between the 2 groups (23 in the oral iron group vs –2 in the placebo group; P = .46). There were also no differences between the 2 groups in terms of the secondary or exploratory end points.

In an effort to explain the difference between the results of the study and those of previous studies showing a benefit of iron, Lewis and colleagues considered many factors. Increased congestion or bleeding did not explain the results, said Lewis, as the rates of both were low in the trial. He added that the ferritin levels in the current study were substantially lower than in other studies, indicating that the iron supplementation was not repleting iron stores. Levels of hepcidin, a key regulator of iron, were elevated, suggesting that resistance to the uptake of iron seemed to be related to hepcidin.

Source: Lewis GD, Anstrom KJ, McNulty S, Hernandez AF, Braunwald E. Oral iron repletion effects on oxygen uptake in heart failure (IRONOUT HF). Presented at: American Heart Association Scientific Sessions 2016; November 12-16, 2016; New Orleans, LA. Abstract LBCT.04.