Iron therapy for the treatment of iron deficiency in chronic heart failure: intravenous or oral?

Abstract

This article considers the use and modality of iron therapy to treat iron deficiency in patients with heart failure, an aspect of care which has received relatively little attention compared with the wider topic of anaemia management. Iron deficiency affects up to 50% of heart failure patients, and is associated with poor quality of life, impaired exercise tolerance, and mortality independent of haematopoietic effects in this patient population. The European Society of Cardiology Guidelines for heart failure 2012 recommend a diagnostic work-up for iron deficiency in patients with suspected heart failure. Iron absorption from oral iron preparations is generally poor, with slow and often inefficient iron repletion; moreover, up to 60% of patients experience gastrointestinal side effects. These problems may be exacerbated in heart failure due to decreased gastrointestinal absorption and poor compliance due to pill burden. Evidence for clinical benefits using oral iron is lacking. I.v. iron sucrose has consistently been shown to improve exercise capacity, cardiac function, symptom severity, and quality of life. Similar findings were observed recently for i.v. ferric carboxymaltose in patients with systolic heart failure and impaired LVEF in the double-blind, placebo-controlled FAIR-HF and CONFIRM-HF trials. I.v. iron therapy may be better tolerated than oral iron, although confirmation in longer clinical trials is awaited. Routine diagnosis and management of iron deficiency in patients with symptomatic heart failure regardless of anaemia status is advisable, and, based on current evidence, prompt intervention using i.v. iron therapy should now be considered.

Keywords: Anaemia; Heart failure; Intravenous; Iron; Iron deficiency; Oral; Quality of life.

Figure 1

Suggested algorithm for diagnosis of iron deficiency in patients with heart failure.– TSAT, transferrin saturation.

Figure 2

Effect of oral or i.v. iron therapy on ‘hepcidin block’ of iron release from macrophages. (A) Under normal circumstances, ∼25 mg of stored iron per day is transported out of macrophages to plasma transferrin by the iron transporter protein ferroportin. (B) In chronic disease, elevated levels of hepcidin cause degradation of ferroportin, restricting ferroportin-mediated transport to ∼15 mg iron/day, (C) The rate of iron absorption from iron therapy is inadequate to influence this ‘hepcidin block’. (D) I.v. iron therapy results in high intracellular iron levels which overcome the ‘hepcidin block’ by stimulating overexpression of ferroportin (modified from Aapro et al.46).

Figure 3

Suggested algorithm for treatment of iron deficiency in patients with heart failure.–,,, TSAT, transferrin saturation.