“The results of the sub analysis are exciting findings for cardiologists and nephrologists who treat these patients, and need to be investigated further,” said the presenter of the analysis Professor Piotr Ponikowski, from the Medical University, 4th Military Hospital (Wroclaw Poland) and President-Elect of the HFA. “Many patients with CHF have renal dysfunction which is strongly related to poor health outcomes. None of the therapies currently recommended for CHF patients have a favourable effect on renal function. Thus, there is great interest in treatments which may have renoprotective properties.”
The Ferinject® Assessment in Patients with Iron Deficiency and Chronic Heart Failure (The FAIR-HF) study, presented at the American Heart Association meeting 2009 by Stefan Anker, was a phase III study demonstrating that treatment with intravenous FCM (Ferinject ®) in iron deficient CHF patients was well tolerated and significantly improved symptoms, NHYA functional class, six-minute-walk distances and quality of life. “The major message from the original study was that iron deficiency is not necessarily linked with anaemia, and that boosting iron levels offers a potential treatment in its own right,” said Ponikowski, who estimated that at least 35 to 40 % of CHF patients have iron deficiency. One theory to explain iron deficiency, he added, was that inflammation related to heart failure impairs the release of iron from stores in the liver and macrophages.
Preliminary findings from the nephrology literature have also suggested that i.v. iron improves renal function in patients with chronic renal disease. Since estimated glomerular filtration rates (eGFR) were evaluated in the original FAIR-HF trial, the investigators decided to explore this aspect of the data more closely in the post hoc FAIR-HF renal function analysis.
In the original FAIR-HF trial, which took place in 75 sites around the world, 459 patients with NYHA class II/III were randomised to i.v. iron (200 mg i.v. weekly in the correction phase , followed by 200mg i.v. iron every 4 weeks in the maintenance phase ) (n=304) or placebo consisting of normal saline (n=155). FAIR-HF was the first double blind placebo control trial to be undertaken exploring whether intravenous iron benefited patients with CHF. “Prior to FAIR-HF blinding the studies had proved difficult because i.v. iron is a black solution. FAIR-HF got round this difficulty by delivering the iron in blacked out syringes,” explained Ponikowski.
Results of the post hoc analysis show that at week 4 the average difference in eGFR between the group receiving the active treatment and the group receiving placebo, was 2.8 +_ 1.5 ml/min/1.73 m2) (P=0.054). At week 12 the average difference in eGFR between the active group and placebo group was 3.0 +- 1.5 ml/min/1.73 m2 (p=0.049) and at week 24 the average difference in eGFR between the active group and placebo group was 4.0 +- 1.7 ml/min/1.73 m2 (p=0.017).
The treatment effect on renal function of Ferinject ®was independent of the level of renal function at the start of the study, or of age, sex, CHF severity, magnitude of left ventricle dysfunction, the presence of anaemia and diabetes mellitus.
“But as yet we don’t have any clear ideas about the mechanisms of how iron would be improving renal function, and further studies are needed to determine potential clinical relevance of our results,”said Ponikowski.