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Anemia and iron deficiency in heart failure: mechanisms and therapeutic approaches

Nature Reviews Cardiology volume 8, pages 485–493 (2011)Cite this article

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Abstract

Anemia and iron deficiency are common in patients with heart failure (HF), and are associated with worse symptoms and adverse outcomes in this population. Although the two can occur together, anemia in HF is often not caused by iron deficiency, and iron deficiency can be present without causing anemia. Erythropoiesis-stimulating agents have been investigated extensively in the past few years and might be of benefit in patients with HF and anemia. However, concerns have arisen regarding the safety of erythropoiesis-stimulating agents in patients with chronic kidney disease and so the results of a large mortality trial are eagerly awaited to provide information on safety in patients with HF. Iron supplementation or replacement is a much older treatment option for patients with HF and anemia, but questions about the safety of intravenous iron, and absorption problems with oral formulations have prevented its widespread use to date. In the past few years, however, new data on the importance of iron deficiency in HF have become available, and a number of studies with intravenous iron have shown promising results. Therefore, this treatment approach is likely to become an attractive option for patients with HF and iron deficiency, both with and without anemia.

Key Points

  • Anemia and iron deficiency are both common and important in the setting of heart failure

  • Anemia is associated with increased morbidity and mortality among patients with heart failure

  • Iron deficiency, both with and without anemia, is also associated with adverse clinical outcomes

  • Treatment of patients with heart failure and anemia with erythropoiesis-stimulating agents could have beneficial clinical effects, but the results of a large-scale ongoing trial (RED-HF) must be awaited

  • Intravenous, but not oral, iron supplementation might be beneficial in the treatment of patients with heart failure and iron deficiency

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Figure 1: Association between hemoglobin response to treatment with erythropoiesis-stimulating agents and outcome in patients with HF.
Figure 2: Role of iron deficiency in the pathogenesis of exercise intolerance.
Figure 3: Influence of iron deficiency on outcome in patients with heart failure.
Figure 4: Effect of intravenous iron (ferric carboxymaltose) in patients with heart failure and iron deficiency in various subgroups (including those with and without anemia).
Figure 5: Clinical events in the Ferinject® Assessment in Patients With IRon Deficiency and Chronic Heart Failure (FAIR-HF).

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  1. Department of Cardiology, University Medical Center Groningen, University of Groningen, PO Box 30.001, 9700RB, Groningen, The Netherlands

    Dirk J. van Veldhuisen

  2. Department of Cardiology, Applied Cachexia Research, Campus Virchow-Klinikum, Charité Universitätsmedizin, Augustenburger Platz 1, D-13353, Berlin, Germany

    Stefan D. Anker

  3. Department of Heart Diseases, Medical University, Military Hospital, Weigla 5, 50-891, Wroclaw, Poland

    Piotr Ponikowski

  4. Department of Renal Medicine, King's College Hospital, SE5 9RS, London, UK

    Iain C. Macdougall

Authors
  1. Dirk J. van Veldhuisen
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  2. Stefan D. Anker
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  3. Piotr Ponikowski
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  4. Iain C. Macdougall
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Contributions

All authors contributed to discussion of content for the article. After the first version, which was written by D. J. van Veldhuisen, all authors researched data to include in the manuscript, and all wrote parts of the manuscript. All authors reviewed and edited the manuscript before submission, and revised the manuscript in response to the peer-reviewers' comments.

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Correspondence to Dirk J. van Veldhuisen.

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Competing interests

D. J. van Veldhuisen, S. D. Anker and P. Ponikowski have been consultants for and received grant/research support from Amgen (manufacturer of darbepoetin alfa) and Vifor (manufacturer of ferric carboxymaltose [intravenous iron]). In addition, S. D. Anker and P. Ponikowski have received speakers bureau (honoraria) from Vifor, and P. Ponikowski has also received speakers bureau from Amgen. I. C. Macdougall has been a consultant for and received speakers bureau and grant/research support from Amgen, Ortho Biotech, Roche and Vifor. In addition, I. C. Macdougall has been a consultant for and received grant/research support from Affymax.

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van Veldhuisen, D., Anker, S., Ponikowski, P. et al. Anemia and iron deficiency in heart failure: mechanisms and therapeutic approaches. Nat Rev Cardiol 8, 485–493 (2011). https://doi.org/10.1038/nrcardio.2011.77

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