Iron Deficiency and Anaemia in Heart Failure: Understanding the FAIR-HF Trial

José González-Costello; Josep Comín-Colet


Eur J Heart Fail. 2010;12(11):1159-1162. 

In This Article

Correction of Anaemia

Great early enthusiasm was generated by Silverberg et al.[5] small initial studies of correction of anaemia in patients with CHF and CKD. He achieved an increase in haemoglobin, functional class, and left ventricular ejection fraction, and decreases in hospitalizations for heart failure, with EPO and intravenous (IV) iron. Erythropoietin-stimulating agents (ESA) received most of the attention from the medical community, and randomized studies were performed assessing the benefits of ESA administration in patients with anaemia and CHF. However, iron replacement was given a secondary role and was only corrected with oral instead of IV iron, except in Silverberg's studies and in a recent study by our group.[6] Two recent meta-analyses of these studies with ESA demonstrated a beneficial effect on heart failure hospitalizations and some signs of symptomatic improvement with no increase in mortality or other adverse events.[7,8] However, in the larger studies, there was no significant improvement in exercise capacity despite the increase in haemoglobin.[9,10] If we add the patients with CHF that were included in the recent TREAT trial, that was designed to assess ESA treatment in diabetic patients with CKD and anaemia, there is a neutral effect on mortality and non-fatal heart failure events.[11] In this situation, an adequately powered clinical trial is needed and hopefully, the RED-HF trial will shed more light on the usefulness of ESA therapy in patients with anaemia and CHF.[12]

These findings are in contrast to the consistent clinical improvements found in recent studies using only IV iron in patients with CHF and iron deficiency (ID), with or without anaemia.[13–17] In the FAIR-HF trial, 459 patients were randomized to receive IV iron as ferric carboxymaltose vs. placebo. Among patients receiving IV iron, 50% reported being much or moderately improved, as compared with 28% of patients receiving placebo, according to the patient global assessment (odds ratio for improvement, 2.51; 95% CI, 1.75–3.61). There was also a significant improvement in the New York Heart Association functional class, in the distance on the 6-minute walk test and quality-of-life assessments. There were no differences in adverse events, but there was a trend for fewer hospitalizations for any cardiovascular disease in the IV iron group. It is important to note that treatment with IV iron was beneficial to both patients with and without anaemia.[16] This finding was also found in the FERRIC-HF trial and is consistent with the concept that impaired physical performance in iron-deficient animal models is due to two facts: (i) the impaired oxidative capacity of the skeletal muscle, as myoglobin, mitochondrial cytochrome, and iron-sulfur content, and total mitochondrial oxidative capacity decreases. (ii) The diminished oxygen transport when anaemia develops.[18] Also, the outcomes assessed in the FAIR-HF trial tended to estimate lower intensity endurance exercise, which correlates tightly with tissue ID. If maximal aerobic capacity had been assessed, probably no benefit would have been found in the non-anaemic group, as this parameter depends fundamentally on the haemoglobin concentration and not on the oxidative capacity of muscle.[19]