Oral Iron Therapy for Heart Failure With Reduced Ejection Fraction

Abstract

Iron deficiency is present in ∼50% of patients with heart failure (HF) and is an independent predictor of mortality. Despite growing recognition of the functional and prognostic significance of iron deficiency, randomized multicenter trials exploring the utility of oral iron supplementation in HF, a therapy that is inexpensive, readily available, and safe, have not been performed. Moreover, patient characteristics that influence responsiveness to oral iron in patients with HF have not been defined. Although results of intravenous iron repletion trials have been promising, regularly treating patients with intravenous iron products is both expensive and poses logistical challenges for outpatients. Herein we describe the rationale for the Oral Iron Repletion effects ON Oxygen UpTake in Heart Failure (IRONOUT HF) Trial. This National Institute of Health-sponsored trial will investigate oral iron polysaccharide compared to matching placebo with the primary endpoint of change in exercise capacity as measured by peak oxygen consumption at baseline and at 16 weeks

Effect of Ferric Carboxymaltose on Exercise Capacity in Patients With Chronic Heart Failure and Iron Deficiency

“… 20 However, until recently, such data in patients with HF were scarce. 21 Recently, the data of the IRONOUT HF study (Oral Iron Repletion Effect on Oxygen Uptake in Heart Failure), (NCT02188784) 22 were published. 23 In that study, 225 patients with symptomatic HF and iron deficiency were randomized to oral iron polysaccharide 150 mg bid or placebo, and the primary end point was change in peak V O 2 after 16 weeks.…”

Iron Therapy in Patients with Heart Failure and Iron Deficiency: Review of Iron Preparations for Practitioners

“…In another study in HF patients with anaemia, the use of oral iron for 1 year was not associated with any clinical benefits in the context of any improvement in NYHA status, measured exercise endurance, oxygen use during exercise, renal function and plasma B-type natriuretic peptide levels, and the need for hospitalization [ 85 ]. Additionally, in the recently presented prospective, randomized clinical trial (IRON-OUT), PIC (150 mg twice daily for 16 weeks) had little effect in replacing iron stores and did not improve peak VO 2 , 6-min walking distance, oxygen kinetics, ventilatory efficiency, and HRQoL score in anaemic HFrEF patients [ 86 , 87 ].…”

Anemia in heart failure: still an unsolved enigma

“…Parenteral iron therapy is recommended in patients found to have iron deficiency. Oral iron therapy has been studied in the trial, IRONOUT (Oral Iron Repletion Effects On Oxygen Uptake in Heart Failure) [ 31 ]. However, in 16 weeks, the 300 mg of oral polysaccharide iron produced only marginal increase in ferritin and transferrin saturation, without any significant increase in exercise capacity or effect on N-terminal pro-B-type natriuretic peptide.…”