Effectiveness of Intravenous iron treatment vs standard care in patients with heart failure and iron deficiency: a randomised, open-label multicentre trial (IRON-MAN)

Heart failure, acute and chronic (CHF), imposes a major burden on patients, their family and carers and the NHS. Following hospitalisation with decompensated CHF, in-hospital mortality is >10% and most will die within two years of index admission. Early readmission rates are high and quality of life often markedly impaired. Iron deficiency is common in patients with CHF and is independently associated with increased mortality and a key determinant of impaired exercise capacity, symptoms and quality of life, even in the absence of anaemia. Small, short-term studies suggest that intravenous (IV) iron improves symptoms in patients with CHF and anaemia secondary to iron deficiency. The largest study to date enrolled 459 out-patients with stable CHF and iron deficiency, with or without anaemia. Compared to placebo, treatment with IV iron (fortnightly) over 24 weeks improved symptoms, functional capacity and quality of life with an acceptable side-effect profile. However, the impact of iron on morbidity and mortality is uncertain and consequently, treatment guidelines unclear. We propose to conduct a randomised trial of IV iron compared to current standard therapy, which is powered to detect differences in the key composite endpoint of heart failure related hospitalisation and cardiovascular mortality, and to determine cost-effectiveness. This will inform both clinical management and international guidelines.