According to the results of a RCT published early online in the New England Journal of Medicine, treating chronic heart failure patients who have iron deficiency with IV iron (ferric carboxymaltose; Ferinject®) improves symptoms, functional capacity, and quality of life.

A total of 459 patients with NYHA class II or III chronic heart failure were enrolled in the Ferinject Assessment in Patients with Iron Deficiency and Chronic Heart Failure (FAIR-HF) trial.  All had a LVEF ≤40% (if class II) or ≤45% (if class III), iron deficiency (ferritin level <100 mcg/L, or 100-299 mcg/L if the transferrin saturation was <20%), and a haemoglobin [Hb] level of 9.5-13.5 g/dL.  They were randomised to received IV ferric carboxymaltose (n=304) or placebo (n=155).  The total iron dose required for iron repletion was calculated at baseline, according to Ganzoni's formula.  The dosing frequency was weekly until iron repletion was achieved (the correction phase) and then every 4 weeks during the maintenance phase.

The primary end points of the study were the self-reported Patient Global Assessment (PGA) and NYHA functional class at week 24; secondary endpoints included the 6-minute walk test, overall score on the Kansas City Cardiomyopathy questionnaire (0-100) and European Quality of Life–5 Dimensions (EQ-5D) Visual Analog Scale (0-100).

The main results were as follows:

• The self-reported PGA at week 24 was improved in the ferric carboxymaltose group, with 50% of patients reporting that they were much or moderately improved, compared to 28% of patients in the placebo group (odds ratio for being in a better rank, 2.51; 95% CI 1.75 to 3.61; P<0.001)

• After adjustment for the baseline value, the NYHA functional class was improved in the ferric carboxymaltose group at week 24, with 47% having a class I or II, as compared with 30% in the placebo group (odds ratio for improvement by one class, 2.40; 95% CI, 1.55 to 3.71; P<0.001)

• Significant improvements were seen with ferric carboxymaltose in the secondary endpoints, including the distance on the 6-minute walk test (mean improvement of 35±8m at week 24 compared to placebo) and quality-of-life assessments.

• Results were similar in patients with anaemia (defined as those with a baseline Hb <12.0g/dL) and those without anaemia

• The rates of death, adverse events, and serious adverse events were similar in the two groups. The hazard ratio for death or first hospitalisation for any cardiovascular reason among patients who received ferric carboxymaltose versus those who received placebo was 0.61 (95% CI 0.32 to 1.18; P=0.14).

The authors note that the fact treatment was beneficial to patients without anaemia suggests that iron deficiency is a valid independent therapeutic target.  They caution that they do not know the limit of Hb up to which iron deficiency is pathophysiologically important; on the basis of their findings they cannot recommend its use in patients with chronic heart failure, iron deficiency, and a HB level above 13.5 g/dL, and recommend this for future research.