Short-Term Intravenous Iron Therapy with Ferric Carboxy-Sucrose versus Oral Iron in Patients with Symptomatic Heart Failure with Reduced Ejection Fraction and Iron Deficiency

Document Type : Original Article

Authors

1 Cardiology department, faculty of medicine, Beni Suef University

2 Cardiology department faculty of medicine Beni suef university

Abstract

To evaluate the efficiency and safety of short-term I.V. iron therapy with ferric carboxy sucrose versus oral iron with ferrous glycine sulfate complex therapy in heart failure (HF) with reduced ejection fraction patients with iron deficiency. A randomized clinical trial on a total of 50 stable HFrEF patients (mean age 50 ±11.6 years) were enrolled in the study between October 2018 to April 2020. The patients were recruited from Cardiology outpatient clinic & inpatient Cardiology department, Beni- Suef University hospital. (25 patients) received oral ferrous glycine sulfate complex and (25 patients) received IV ferric carboxy sucrose. All patients were subjected to; recording of demographic data, full clinical examination, and laboratory and imaging investigations and six-minute walk test (6MWT). Results showed that apart from EF, all parameters improved significantly after iron therapy (regardless of route of therapy) as regards LVED, LVES, serum iron, serum ferritin, transferrin saturation, 6MWT & NYHA classification. There was a significant negative correlation between the improvement of transferrin saturation & the NYHA classification after intravenous iron therapy. There was a significant weak positive correlation between iron improvement & 6MWT improvement in all 50 patients. Also, a trend towards a weak positive correlation between iron improvement by intravenous route & improvement of 6 MWT was observed. Regardless the route of administration, iron therapy (I.V. iron therapy in the form of ferric carboxy-sucrose or oral iron in the form of ferrous glycine sulfate complex) is safe & effective in improving functional capacity of HFrEF patients with iron deficiency. This improvement is proportional to the degree of improvement in transferring saturation obtained by IV ferric carboxy-sucrose therapy.

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    1. Bleumink G, Knetsch A, Sturkenboom M, et al. Quantifying the heart failure epidemic: prevalence, incidence rate, lifetime risk and prognosis of heart failure: The Rotterdam Study. European heart journal. 2004;25(18):1614-9.
    2. McMurray J, Adamopoulos S, Anker S, et al. ESC Committee for Practice Guidelines. ESC Guidelines for the diagnosis and treatment of acute and chronic heart failure 2012: The Task Force for the Diagnosis and Treatment of Acute and Chronic Heart Failure 2012 of the European Society of Cardiology. Developed in collaboration with the Heart Failure Association (HFA) of the ESC. Eur Heart J. 2012;33(14):1787-847.
    3. Tavazzi L, Senni M, Metra M, et al. Multicenter prospective observational study on acute and chronic heart failure: one-year followup results of IN-HF (Italian Network on Heart Failure) outcome registry. Circulation: Heart Failure. 2013;6(3):473-81.
    4. Shanmugam N. Impact on Patient Care: The 2016 European Heart Failure Guidelines. European Cardiology Review. 2017;12(2):78.
    5. van Deursen V, Urso R, Laroche C, et al. Co‐morbidities in patients with heart failure: an analysis of the European Heart Failure Pilot Survey. European journal of heart failure. 2014;16(1):103-11.
    6. Andrews N. Disorders of iron metabolism. New England Journal of Medicine. 1999;341(26):1986-95.
    7. Baker J, Ghio A. Iron homoeostasis in rheumatic disease. Rheumatology. 2009;48(11):1339-44.
    8. Ponikowski P, Van Veldhuisen D, 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. European heart journal. 2015;36(11):657-68.
    9. Ponikowska B, Suchocki T, Paleczny B, et al. Iron status and survival in diabetic patients with coronary artery disease. Diabetes care. 2013;36(12):4147-56.
    10. Klip I, Comin-Colet J, Voors A, et al. Iron deficiency in chronic heart failure: an international pooled analysis. American heart journal. 2013;165(4):575-82. e3.
    11. Okonko D, Mandal A, Missouris C, et al. Disordered iron homeostasis in chronic heart failure: prevalence, predictors, and relation to anemia, exercise capacity, and survival. Journal of the American College of Cardiology. 2011;58(12):1241-51.
    12. Kasner M, Aleksandrov A, Westermann D, et al. Functional iron deficiency and diastolic function in heart failure with preserved ejection fraction. International journal of cardiology. 2013;168(5):4652-7.
    13. Jankowska E, Kasztura M, Sokolski M, et al. Iron deficiency defined as depleted iron stores accompanied by unmet cellular iron requirements identifies patients at the highest risk of death after an episode of acute heart failure. European heart journal. 2014;35(36):2468-76.
    14. Van Veldhuisen D, Anker S, Ponikowski P, et al. Anemia and iron deficiency in heart failure: mechanisms and therapeutic approaches. Nature Reviews Cardiology. 2011;8(9):485-93.
    15. Jankowska E, Rozentryt P, Witkowska A, et al. Iron deficiency predicts impaired exercise capacity in patients with systolic chronic heart failure. Journal of cardiac failure. 2011;17(11):899-906.
    16. Van Wyck D, Roppolo M, Martinez C, et al. A randomized, controlled trial comparing IV iron sucrose to oral iron in anemic patients with nondialysisdependent CKD. Kidney international. 2005;68(6):2846-56.
    17. Breymann C, Gliga F, Bejenariu C, et al. Comparative efficacy and safety of intravenous ferric carboxymaltose in the treatment of postpartum iron deficiency anemia. International Journal of Gynecology & Obstetrics. 2008;101(1):67-73.
    18. Dhanani J, Ganguly B, Chauhan L. Comparison of efficacy and safety of two parenteral iron preparations in pregnant women. Journal of pharmacology & pharmacotherapeutics. 2012;3(4):314.
    19. Drozd M, Jankowska E, Banasiak W, et al. Iron therapy in patients with heart failure and iron deficiency: review of iron preparations for practitioners. American Journal of Cardiovascular Drugs. 2017;17(3):183-201.
    20. Kulnigg S, Stoinov S, Simanenkov V, et al. A novel intravenous iron formulation for treatment of anemia in inflammatory bowel disease: the ferric carboxymaltose (FERINJECT®) randomized controlled trial. American Journal of Gastroenterology. 2008;103(5):1182-92.
    21. Collings R, Harvey L, Hooper L, et al. The absorption of iron from whole diets: a systematic review. The American journal of clinical nutrition. 2013;98(1):65-81.
    22. Johnson-Wimbley T, Graham D. Diagnosis and management of iron deficiency anemia in the 21st century. Therapeutic advances in Gastroenterology. 2011;4(3):177-84.
    23. McDonagh T, Macdougall I. Iron therapy for the treatment of iron deficiency in chronic heart failure: intravenous or oral? Eur J Heart Fail. 2015; 17:248–262.
    24. Lewis G, Malhorta R, Hernandez A, 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; 317:1958–1966.
    25. Bolger A, Bartlett F, Penston H, et al. Intravenous iron alone for the treatment of anemia in patients with chronic heart failure. J Am Coll Cardiol. 2006 Sep 19;48(6):1225-7
    26. Usmanov R, Zueva E, Silverberg D, et al. 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 Mar Apr;21(2):236-42.
    27. Toblli J, Lombraña A, Duarte P, et al. Intravenous iron reduces NTprobrain natriuretic peptide in anemic patients with chronic heart failure and renal insufficiency. J Am Coll Cardiol. 2007 Oct 23;50(17):1657-65.
    28. Toblli J, Di Gennaro F, Rivas C2. Changes in Echocardiographic Parameters in Iron Deficiency Patients with Heart Failure and Chronic Kidney Disease Treated with Intravenous Iron. Heart Lung Circ. 2015 Jul;24(7):68695
    29. Okonko D, Grzeslo A, Witkowski T, 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, observerblinded trial. J Am Coll Cardiol. 2008 Jan 15;51(2):103-12.
    30. Martini A, Ravelli A, Di Fuccia G, et al. Intravenous iron therapy for severe anemia in systemic-onset juvenile chronic arthritis. Lancet. 1994;344:1052–4
    31. Schroder O, Mickisch O, Seidler U, et al. Intravenous iron sucrose versus oral iron supplementation for the treatment of iron deficiency anemia in patients with inflammatory bowel disease-a randomized, controlled, open-label, multicenter study. Am J Gastroenterol. 2005;100:2503–9.
    32. Κοτζαδάμης, Δημήτριος Νικολάου. Effects of intravenous iron therapy in patients with heart failure and iron deficiency: A systematic review and metaanalysis of randomized controlled trials. No. GRI-2020- 27026. Aristotle University of Thessaloniki, 2020.