Patients with heart failure may be prone to the development of iron deficiency either as a consequence of depletion of iron stores, defective iron absorption, or the reduced availability of iron recycled in the reticuloendothelial system. Iron plays a key role in oxygen uptake, transport, and storage, and oxidative metabolism in the skeletal muscle, as well as being involved in erythropoiesis.
To test the hypothesis that correction of iron deficiency (defined by low serum ferritin and transferrin saturation) confers symptomatic benefit in patients with chronic heart failure, the FAIR-HF (Ferinject Assessment in Patients with Iron Deficiency and Chronic Heart Failure) investigators recruited 459 patients with NYHA class II or III heart failure with an ejection fraction below 45%. The trial was a multicentre, double-blind placebo controlled study that gave intravenous iron (ferric carboxymaltose, 200mg) or placebo to patients with an initial haemoglobin level of <135g/L. The initial treatment was for 8 to 12 weeks, depending on the patient’s iron deficit, followed by treatment every four weeks up to a total of 26 weeks of treatment.
The results demonstrated both early and sustained benefits in the treatment arm for the study’s two primary outcomes: an improvement in the self-reported Patient Global Assessment scale, and a decrease in NYHA functional class at 24 weeks (odds ratio for NYHA improvement by one class, 2.40; P<0.001). Secondary end points, including distance covered on the 6-minute walk test, also showed improvement. No increase in adverse events was seen, and the drug was well tolerated.
Ferric carboxymaltose therapy given to patients with symptomatic heart failure and anaemia improved both subjective and objective measures of disease severity. Whether cheaper formulations of oral iron will be as effective or whether ferric carboxymaltose treatment will also show benefit on harder end-points such as re-hospitalisation and even mortality will be tested in future trials. However, in confirming the results of earlier small scale studies, this trial makes a convincing case that the correction of anemia is a high priority in the treatment of heart failure.
• Anker SD, Comin Colet J, Filippatos G, Willenheimer R, Dickstein K, Drexler H, Lüscher TF, Bart B, Banasiak W, Niegowska J, Kirwan BA, Mori C, von Eisenhart Rothe B, Pocock SJ, Poole-Wilson PA, Ponikowski P; the FAIR-HF Trial Investigators. Ferric Carboxymaltose in Patients with Heart Failure and Iron Deficiency N Engl J Med. 2009 Dec 17;361(25):2436-2448