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Iron Deficiency in Heart Failure: to Treat or Not to Treat?

  • Heart Failure (W Tang, Section Editor)
  • Published:
Current Treatment Options in Cardiovascular Medicine Aims and scope Submit manuscript

Abstract

Purpose of review

This review will highlight the frequency and prognostic importance of iron deficiency in patients with chronic heart failure. An overview of the evidence surrounding the use of both oral and intravenous iron will be presented together with discussion around what further data are required to establish what is the optimal long-term treatment strategy.

Recent findings

Several recent randomised controlled studies have suggested that intravenous iron therapy in iron deficient patients with chronic heart failure and reduced ejection fraction can improve symptoms and quality of life, at least in the short term. There is no evidence of benefit from oral iron.

Summary

Iron deficiency is common in patients with chronic heart failure and is associated with a worse prognosis. Whilst oral iron therapy has been shown to be of no benefit, randomised controlled trials suggest significant improvement in symptoms and quality of life with intravenous iron treatment over 6–12 months. Data are lacking on long-term efficacy, safety and impact on hard outcomes such as death and hospitalisation. Four large trials are currently recruiting patients and will provide definitive answers to these outstanding questions.

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References and Recommended Reading

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  1. Jankowska EA, von Haehling S, Anker SD, Macdougall IC, Ponikowski P. Iron deficiency and heart failure: diagnostic dilemmas and therapeutic perspectives. Eur Heart J. 2013;34(11):816–29.

    Article  PubMed  CAS  Google Scholar 

  2. Felker GM, Adams KF, Gattis WA, O’Connor CM. Anemia as a risk factor and therapeutic target in heart failure. J Am Coll Cardiol. 2004;44(5):959–66.

    Article  PubMed  Google Scholar 

  3. Tang YD, Katz SD. Anemia in chronic heart failure: prevalence, etiology, clinical correlates, and treatment options. Circulation. 2006;113(20):2454–61.

    Article  PubMed  Google Scholar 

  4. Sharma R, Francis DP, Pitt B, Poole-Wilson PA, Coats AJ, Anker SD. Haemoglobin predicts survival in patients with chronic heart failure: a substudy of the ELITE II trial. Eur Heart J. 2004;25(12):1021–8.

    Article  PubMed  CAS  Google Scholar 

  5. O'Meara E, Clayton T, McEntegart MB, McMurray JJ, Lang CC, Roger SD, et al. Clinical correlates and consequences of anemia in a broad spectrum of patients with heart failure: results of the Candesartan in Heart Failure: Assessment of Reduction in Mortality and Morbidity (CHARM) Program. Circulation. 2006;113(7):986–94.

    Article  PubMed  Google Scholar 

  6. von Haehling S, van Veldhuisen DJ, Roughton M, Babalis D, de Boer RA, Coats AJ, et al. Anaemia among patients with heart failure and preserved or reduced ejection fraction: results from the SENIORS study. Eur J Heart Fail. 2011;13(6):656–63.

    Article  Google Scholar 

  7. Anand IS, Kuskowski MA, Rector TS, Florea VG, Glazer RD, Hester A, et al. Anemia and change in hemoglobin over time related to mortality and morbidity in patients with chronic heart failure: results from Val-HeFT. Circulation. 2005;112(8):1121–7.

    Article  PubMed  CAS  Google Scholar 

  8. Go AS, Yang J, Ackerson LM, Lepper K, Robbins S, Massie BM, et al. Hemoglobin level, chronic kidney disease, and the risks of death and hospitalization in adults with chronic heart failure: the Anemia in Chronic Heart Failure: Outcomes and Resource Utilization (ANCHOR) Study. Circulation. 2006;113(23):2713–23.

    Article  PubMed  CAS  Google Scholar 

  9. van der Meer P, Groenveld HF, Januzzi JL, van Veldhuisen DJ. Erythropoietin treatment in patients with chronic heart failure: a meta-analysis. Heart. 2009;95(16):1309–14.

    Article  PubMed  CAS  Google Scholar 

  10. Ponikowski P, Anker SD, Szachniewicz J, Okonko D, Ledwidge M, Zymlinski R, et al. Effect of darbepoetin alfa on exercise tolerance in anemic patients with symptomatic chronic heart failure: a randomized, double-blind, placebo-controlled trial. J Am Coll Cardiol. 2007;49(7):753–62.

    Article  PubMed  CAS  Google Scholar 

  11. Swedberg K, Young JB, Anand IS, Cheng S, Desai AS, Diaz R, et al. Treatment of anemia with darbepoetin alfa in systolic heart failure. N Engl J Med. 2013;368(13):1210–9.

    Article  PubMed  CAS  Google Scholar 

  12. Kang CK, Pope M, Lang CC, Kalra PR. Iron deficiency in heart failure: efficacy and safety of intravenous iron therapy. Cardiovasc Ther. 2017;35(6)

  13. Cleland JG, Zhang J, Pellicori P, Dicken B, Dierckx R, Shoaib A, et al. Prevalence and outcomes of anemia and hematinic deficiencies in patients with chronic heart failure. JAMA Cardiol. 2016;1:539–47.

    Article  PubMed  Google Scholar 

  14. Anker SD, Comin Colet J, Filippatos G, Willenheimer R, Dickstein K, Drexler H, et al. Ferric carboxymaltose in patients with heart failure and iron deficiency. N Engl J Med. 2009;361(25):2436–48.

    Article  PubMed  CAS  Google Scholar 

  15. Ponikowski P, van Veldhuisen DJ, Comin-Colet J, Ertl G, Komajda M, Mareev V, 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(11):657–68.

    Article  PubMed  CAS  Google Scholar 

  16. Jankowska EA, Rozentryt P, Witkowska A, Nowak J, Hartmann O, Ponikowska B, et al. Iron deficiency: an ominous sign in patients with systolic chronic heart failure. Eur Heart J. 2010;31(15):1872–80.

    Article  PubMed  CAS  Google Scholar 

  17. Okonko DO, Mandal AK, Missouris CG, Poole-Wilson PA. Disordered iron homeostasis in chronic heart failure: prevalence, predictors, and relation to anemia, exercise capacity, and survival. J Am Coll Cardiol. 2011;58(12):1241–51.

    Article  PubMed  CAS  Google Scholar 

  18. Klip IT, Comin-Colet J, Voors AA, Ponikowski P, Enjuanes C, Banasiak W, et al. Iron deficiency in chronic heart failure: an international pooled analysis. Am Heart J. 2013;165(4):575–82.e3.

    Article  PubMed  CAS  Google Scholar 

  19. McDonagh T, Macdougall IC. Iron therapy for the treatment of iron deficiency in chronic heart failure: intravenous or oral? Eur J Heart Fail. 2015;17(3):248–62.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  20. Ganz T, Nemeth E. Hepcidin and disorders of iron metabolism. Annu Rev Med. 2011;62:347–60.

    Article  PubMed  CAS  Google Scholar 

  21. Nemeth E, Tuttle MS, Powelson J, Vaughn MB, Donovan A, Ward DM, et al. Hepcidin regulates cellular iron efflux by binding to ferroportin and inducing its internalization. Science. 2004;306(5704):2090–3.

    Article  PubMed  CAS  Google Scholar 

  22. Filippatos G, Farmakis D, Colet JC, Dickstein K, Lüscher TF, Willenheimer R, et al. Intravenous ferric carboxymaltose in iron-deficient chronic heart failure patients with and without anaemia: a subanalysis of the FAIR-HF trial. Eur J Heart Fail. 2013;15(11):1267–76.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  23. Beck-da-Silva L, Piardi D, Soder S, Rohde LE, Pereira-Barretto AC, de Albuquerque D, et al. IRON-HF study: a randomized trial to assess the effects of iron in heart failure patients with anemia. Int J Cardiol. 2013;168(4):3439–42.

    Article  PubMed  Google Scholar 

  24. • Lewis GD, Malhotra R, Hernandez AF, McNulty SE, Smith A, Felker GM, et al. 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):1958–66. The IRONOUT trial is the only large scale randomised study of oral iron use in heart failure and showed no benefit.

  25. Bolger AP, Bartlett FR, Penston HS, O'Leary J, Pollock N, Kaprielian R, et al. Intravenous iron alone for the treatment of anemia in patients with chronic heart failure. J Am Coll Cardiol. 2006;48(6):1225–7.

    Article  PubMed  CAS  Google Scholar 

  26. Toblli JE, Lombraña A, Duarte P, Di Gennaro F. Intravenous iron reduces NT-pro-brain natriuretic peptide in anemic patients with chronic heart failure and renal insufficiency. J Am Coll Cardiol. 2007;50(17):1657–65.

    Article  PubMed  CAS  Google Scholar 

  27. Okonko DO, Grzeslo A, Witkowski T, Mandal AK, Slater RM, Roughton M, et al. Effect of intravenous iron sucrose on exercise tolerance in anemic and nonanemic patients with symptomatic chronic heart failure and iron deficiency FERRIC-HF: a randomized, controlled, observer-blinded trial. J Am Coll Cardiol. 2008;51(2):103–12.

    Article  PubMed  CAS  Google Scholar 

  28. Usmanov RI, Zueva EB, Silverberg DS, Shaked M. Intravenous iron without erythropoietin for the treatment of iron deficiency anemia in patients with moderate to severe congestive heart failure and chronic kidney insufficiency. J Nephrol. 2008;21(2):236–42.

    PubMed  CAS  Google Scholar 

  29. •• Jankowska EA, Tkaczyszyn M, Suchocki T, Drozd M, von Haehling S, Doehner W, et al. Effects of intravenous iron therapy in iron-deficient patients with systolic heart failure: a meta-analysis of randomized controlled trials. Eur J Heart Fail. 2016. CONFIRM-HF was a randomised controlled trial of intravenous iron in patients with heart failure and reduced ejection fraction and a subsequent meta-analysis included these data together with that from FAIR-HF. These demonstrated improved symptoms and raised the possibility of reduced hospitalization and improved mortality.;18:786–95.

    Article  PubMed  CAS  Google Scholar 

  30. van Veldhuisen DJ, Ponikowski P, van der Meer P, Metra M, Böhm M, Doletsky A, et al. Effect of ferric carboxymaltose on exercise capacity in patients with chronic heart failure and iron deficiency. Circulation. 2017;136(15):1374–83.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  31. Ponikowski P, Voors AA, Anker SD, Bueno H, Cleland JG, Coats AJ, et al. 2016 ESC Guidelines for the diagnosis and treatment of acute and chronic heart failure: The Task Force for the diagnosis and treatment of acute and chronic heart failure of the European Society of Cardiology (ESC). Developed with the special contribution of the Heart Failure Association (HFA) of the ESC. Eur J Heart Fail 2016;18(8):891–975.

  32. Yancy CW, Jessup M, Bozkurt B, Butler J, Casey DE, Colvin MM, et al. 2017 ACC/AHA/HFSA focused update of the 2013 ACCF/AHA guideline for the management of heart failure: a report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines and the Heart Failure Society of America. J Am Coll Cardiol. 2017;70(6):776–803.

    Article  PubMed  Google Scholar 

  33. Auerbach M, Macdougall I. The available intravenous iron formulations: history, efficacy, and toxicology. Hemodial Int. 2017;21(Suppl 1):S83–92.

    Article  PubMed  Google Scholar 

  34. New recommendations to manage risk of allergic reactions with intravenous iron-containing medicines. European Medicines Agency; 2013. Contract No.: 579491.

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Authors and Affiliations

  1. Department of Cardiology, John Radcliffe Hospital, Oxford University Hospitals NHS Foundation Trust, Level 2, Headley Way, Headington, Oxford, OX3 9DU, UK

    Michael Pope BM, BSc, MRCP

  2. Portsmouth Hospitals NHS Trust, Portsmouth, UK

    Paul R. Kalra MD FRCP

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  1. Michael Pope BM, BSc, MRCP
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  2. Paul R. Kalra MD FRCP
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Correspondence to Michael Pope BM, BSc, MRCP.

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This article does not contain any studies with human or animal subjects performed by any of the authors.

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This article is part of the Topical Collection on Heart Failure

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Pope, M., Kalra, P.R. Iron Deficiency in Heart Failure: to Treat or Not to Treat?. Curr Treat Options Cardio Med 20, 65 (2018). https://doi.org/10.1007/s11936-018-0661-8

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  • DOI: https://doi.org/10.1007/s11936-018-0661-8

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