Expert Opinion

Rachel Bijou, MD, Attending Cardiologist, Columbia University Irving Medical Center, New York, NY. Dr. Bijou specializes in advanced heart failure and transplant cardiology.

Although oral iron supplementation is accessible and inexpensive, the efficacy of oral therapy for heart failure with reduced ejection fraction is not established. The heightened activity of cytokines raises levels of hepcidin leading to reduced iron absorption. Iron is associated with intestinal side effects leading to non-compliance with therapy. Oral iron absorption is impaired by certain foods and medications and the presence of bowel edema.

Most importantly, there is no clinical evidence of oral iron benefit in heart failure patients. In the placebo controlled IRONOUT-HF trial,1 oral iron polysaccharide supplementation did not improve exercise capacity. In contrast, there are several many placebo-controlled trials demonstrating efficacy of IV iron supplementation.2,3 


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IV ferric carboxymaltose (IV FCM) is indicated to treat IDA in a setting of intolerance to oral iron or unsatisfactory response to oral iron. The dose for individuals >50kg is 750mg on day 1 and a repeat dose after at least 7 days (maximum: 1500mg per course).

For the largest and most recent placebo-controlled HF trials, IV FCM is the agent of choice; the dose is based upon weight and hemoglobin. The most common dosing intervals is 6 weeks for 2-4 doses. Serious adverse side effects have not been observed in these short-term studies and there is no data on the safety of long-term therapy.

In the past, iron dextran, a high molecular weight product, was frequently used as a supplement; it was associated with allergic and sometimes anaphylactic reactions and is not recommended.4

It is also important to note that erythropoietin-stimulating agents are not recommended for patients with HF and anemia, as these agents are sometimes prothrombotic and have shown limited clinical efficacy in heart failure. 

References:

  1. Lewis GD, Malhotra R, Hernandez AF. Effect of Oral Iron Repletion on Exercise Capacity in Patients with Heart Failure with Reduced Ejection Fraction and Iron Deficiency: the IRONOUT HF Randomized Clinical Trial. JAMA. 2017;317(19):1958-1966.
  2. Ponikowski P, van Veldhuisen DJ, Comin-Colet J, et al. Beneficial effects of long-term intravenous iron therapy with ferric carboxymaltose in patients with symptomatic heart failure and iron deficiency. Eur Heart J. 2015;36:357-368.
  3. Kapoor M, Schleinitz MD, Gemignani A, et al. Outcomes of patients with chronic heart failure and iron deficiency treated with intravenous iron: a metaanalysis. Cardiovasc Hematol Disord Drug Targets. 2013;14:35-44.
  4. Wang C, Graham DJ, Kane RC, et al. Comparative risk of anaphylactic reactions associated with intravenous iron products. JAMA. 2015;314(19):2062-2068.