Intravenous iron for treatment of anemia in heart failure

October 22, 2007 By Benjamin A. Olenchock, M.D. Ph.D. [mailto:bolenchock@partners.org]

“Buenes Aires” A new randomized, placebo-controlled trial has demonstrated that intravenous iron therapy significantly improved functional status and reduced NT-proBNP levels in heart failure patients. The study selected patients with co-morbid chronic anemia, chronic kidney disease, and iron studies consistent with iron-deficiency. At six-months follow-up, this small study showed significant improvement in hemoglobin concentration, iron indices, exercise capacity, NT-proBNP levels, and NYHA functional class.

Anemia is a common problem in heart failure patients and is associated with increased mortality. The pathogenesis is multifactorial - dilutional anemia from excess intravascular fluid, chronic inflammation, and iron-deficiency all contribute. It is estimated that iron-deficiency is present in up to one-third of heart failure patients, but the diagnosis is frequently missed when relying on ferritin levels, which might be falsely elevated in heart failure patients. Ongoing studies are testing whether administration of recombinant erythropoietin is beneficial in heart failure patients. In the wake of the CHOIR study, however, concern has been raised regarding pleotropic effects of recombinant erythropoietin. The current study has assessed whether IV iron alone is beneficial in this patient population.

The authors selected patients with NYHA class II-IV heart failure, hemoglobin < 12.5 for men or < 11.5 for women, creatinine clearance < 90 cc/min, and either ferritin < 100 or transferring saturation < 20%. Exclusions included patients requiring hemodialysis or those who recently received iron or erythropoietin therapy. They randomize 40 patients to weekly infusions of saline or 200 mg iron sucrose for five weeks. Baseline characteristics were similar between the two groups, with the majority of patients having ischemic heart disease and the average creatinine clearance of near 40 cc/min. At 6-months follow-up, patient who received IV iron had significant improvements in hemoglobin levels (11.8 vs. 9.8 g/dL), transferring saturation (0.25 vs. 0.20), NT-proBNP levels (118 vs. 451 pg/ml), NYHA functional class (2.0 vs. 3.3), and 6-minute walk test (240 vs 185 minutes). In short, the authors noted improvement in almost every measurement in the patients who received IV iron. Interestingly, they noted a strong inverse correlation between hemoglobin concentration and NT-proBNP level.

This was a small study with highly selected patients, however the results were quite encouraging. Additionally, this was the first randomized, placebo-controlled trial to address the use of IV iron in this patient population. In patients with chronic kidney disease, iron-deficiency and impaired iron utilization are common in patients in patients with normal iron studies. It would be interesting to know if IV iron is beneficial in heart failure patients with anemia and normal iron indices, or heart failure patients with lesser degrees of co-morbid kidney disease. The observation that IV-iron improves NT-proBNP levels is interesting, and speaks to the interconnections between inflammation, anemia, impaired hemodynamics, activation of the renin-angiotensin system. Ongoing studies will help clarify the role of erythropoietin and IV iron in heart failure patients with anemia.

.Toblli et al. Intravenous Iron Reduces NT-Pro-Brain Natriuretic Peptide in Anemic Patients With Chronic Heart Failure and Renal Insufficiency. JACC Vol 50, No. 17, 2007 pages 1657-65.