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Is oral iron always the best option?
¿Es el hierro oral siempre la mejor opción?
J. Grau Amorós
Grupo de Trabajo de Insuficiencia Cardiaca y Fibrilación auricular, Sociedad Española de Medicina Interna
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Ena, R. Gómez-Huelgas" "autores" => array:2 [ 0 => array:2 [ "nombre" => "J." "apellidos" => "Ena" ] 1 => array:2 [ "nombre" => "R." "apellidos" => "Gómez-Huelgas" ] ] ] ] ] "idiomaDefecto" => "en" "Traduccion" => array:1 [ "es" => array:9 [ "pii" => "S0014256519302279" "doi" => "10.1016/j.rce.2019.09.001" "estado" => "S300" "subdocumento" => "" "abierto" => array:3 [ "ES" => false "ES2" => false "LATM" => false ] "gratuito" => false "lecturas" => array:1 [ "total" => 0 ] "idiomaDefecto" => "es" "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S0014256519302279?idApp=WRCEE" ] ] "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S2254887419302589?idApp=WRCEE" "url" => "/22548874/0000022000000001/v1_202002130124/S2254887419302589/v1_202002130124/en/main.assets" ] "en" => array:12 [ "idiomaDefecto" => true "cabecera" => "<span class="elsevierStyleTextfn">EDITORIAL</span>" "titulo" => "Is oral iron always the best option?" "tieneTextoCompleto" => true "paginas" => array:1 [ 0 => array:2 [ "paginaInicial" => "27" "paginaFinal" => "28" ] ] "autores" => array:1 [ 0 => array:3 [ "autoresLista" => "J. Grau Amorós" "autores" => array:1 [ 0 => array:3 [ "nombre" => "J." "apellidos" => "Grau Amorós" "email" => array:1 [ 0 => "11426jga@comb.cat" ] ] ] "afiliaciones" => array:1 [ 0 => array:2 [ "entidad" => "Grupo de Trabajo de Insuficiencia Cardiaca y Fibrilación auricular, Sociedad Española de Medicina Interna" "identificador" => "aff0005" ] ] ] ] "titulosAlternativos" => array:1 [ "es" => array:1 [ "titulo" => "¿Es el hierro oral siempre la mejor opción?" ] ] "textoCompleto" => "<span class="elsevierStyleSections"><p id="par0005" class="elsevierStylePara elsevierViewall">The administration of iron for therapeutic goals traces back several centuries; however, the likelihood of severe hypersensitivity reactions has limited the use of intravenous iron until recent years. The development of new formulations without risk has resulted in a marked increase in scientific publications in the past 20 years. Most authors prudently recommend starting with oral treatment, not only because of its lower cost but also for being the most physiological pathway and due to the risk of toxicity in repeated intravenous treatments. A couple of articles published in the <span class="elsevierStyleSmallCaps">Revista Clínica Española</span> support this approach,<a class="elsevierStyleCrossRefs" href="#bib0075"><span class="elsevierStyleSup">1,2</span></a> the first of which revealed a number of gaps in our current understanding of iron metabolism in heart failure, especially in recognizing and treating tissue iron deficiency. The study also warns of the potential toxicity risk of using massive doses of intravenous iron, defending the use of oral iron as the first option, despite the results of the IRONOUT-HF study that failed to improve the maximal tissue oxygen uptake or increase the distance travelled by patients in the 6-min walking test. In the other article, the authors revealed the consensus of the Spanish Erythropathology Group of the Spanish Society of Hematology and Hemotherapy on managing iron deficiency in various conditions. This meritorious effort in synthesizing the consensus has resulted in a document that can be quickly consulted to determine the best approach for our daily clinical practice. The authors also recommended the use of orally administered iron, reserving intravenous administration for therapeutic failure and the inability to digestively absorb iron.</p><p id="par0010" class="elsevierStylePara elsevierViewall">However, is this reserving of intravenous iron solidly grounded? Is the use of oral iron more cost-effective than intravenous administration in clinical practice? Do the savings resulting from the lower cost of oral medication justify the delay in feeling the benefits of iron? Is there sufficient evidence to support the fear of toxicity in intermittent intravenous iron administration?</p><p id="par0015" class="elsevierStylePara elsevierViewall">The frequent gastrointestinal intolerance to oral iron is well known and results in therapeutic noncompliance and frequent treatment abandonment. There are administration strategies that decrease the intolerance, but if they do not improve tolerance and the iron deposits are not replenished then the clinician has to resort to intravenous iron. With this, the necessary treatment has been delayed, in the best of cases, by a month. This situation entails prolonging the work leave for young adults and, for older individuals, increasing the time during which there is a risk of frailty. This older population is increasingly numerous in our consultations and has a high incidence of anemia and iron deficiency, without a specific etiological diagnosis in up to 30% of cases.<a class="elsevierStyleCrossRef" href="#bib0085"><span class="elsevierStyleSup">3</span></a> This group often has chronic ailments, where iron metabolism is complicated, with several etiological mechanisms in the onset of anemia, with or without iron deficiency.<a class="elsevierStyleCrossRefs" href="#bib0075"><span class="elsevierStyleSup">1,2</span></a> In this scenario, it is easy to understand why oral iron in the IRONOUT-HF study did not achieve the objectives achieved with intravenous iron in the trial FAIR-HF,<a class="elsevierStyleCrossRefs" href="#bib0090"><span class="elsevierStyleSup">4,5</span></a> calling into question the efficacy of oral iron in correcting the needs of the cardiomyocyte. This finding also revealed the need for improving the study of iron deficiencies in the clinic. The measurement of soluble transferrin receptors should be incorporated in all clinical analysis laboratories, and a standardized test to measure hepcidin levels is an increasingly obvious necessity.</p><p id="par0020" class="elsevierStylePara elsevierViewall">Another discussion point is intravenous iron toxicity after the emergence of formulations with complex carbohydrate cores that more strongly bind to elemental iron, limiting the release (at subclinical levels) of free iron. A meta-analysis of published trials on the adverse effects of these formulations has shown no greater risk of severe adverse events compared with controls, and, as expected, the rate of gastrointestinal reactions was significantly lower.<a class="elsevierStyleCrossRef" href="#bib0100"><span class="elsevierStyleSup">6</span></a> This result does not preclude being careful and vigilant as to the adverse effects with very low incidence rates that are usually missed in the limited follow-ups of clinical trials.</p><p id="par0025" class="elsevierStylePara elsevierViewall">Given iron's ability to promote oxidative stress in endothelial cells, there is the worrying possibility that the use of iron increases the risk of cardiovascular events. Once again, a meta-analysis of trials with high cardiovascular risk populations, such as patients undergoing dialysis, found no evidence to support this hypothesis.<a class="elsevierStyleCrossRef" href="#bib0105"><span class="elsevierStyleSup">7</span></a></p><p id="par0030" class="elsevierStylePara elsevierViewall">Another of the limitations classically put forward for restricting the use of intravenous iron therapy is the likelihood of increasing the incidence of infections, given that free iron is an essential nutrient, not only for humans but also for most of its microbial pathogens.<a class="elsevierStyleCrossRef" href="#bib0110"><span class="elsevierStyleSup">8</span></a> However, none of the meta-analyses conducted on various diseases has confirmed this possibility. Furthermore, a recent trial examining the safety of high doses of intravenous iron in patients undergoing hemodialysis also found no differences in hospitalizations for infection between the two treatment regimens.<a class="elsevierStyleCrossRef" href="#bib0115"><span class="elsevierStyleSup">9</span></a> Moreover, in patients with inflammatory bowel disease, intravenous iron therapy produced no changes in the gut microbiome when compared with oral iron,<a class="elsevierStyleCrossRef" href="#bib0120"><span class="elsevierStyleSup">10</span></a> an emerging factor in many aspects, including cardiovascular risk.</p><p id="par0035" class="elsevierStylePara elsevierViewall">Lastly, we have cost-benefit studies in favor of the use of intravenous iron in inflammatory bowel disease, chronic renal failure and chronic heart failure accompanied by anemia or iron deficiency without anemia. The savings in the total cost of medical care more than compensates for the higher cost of the drug.<a class="elsevierStyleCrossRefs" href="#bib0125"><span class="elsevierStyleSup">11–14</span></a></p><p id="par0040" class="elsevierStylePara elsevierViewall">In conclusion, the simplicity and convenience of oral iron administration is not the only factor to consider; in the practice of medicine, generalizing is risky. Scientific guidelines and recommendations are necessary and highly useful, but the medical act is individualized. All adjuvant factors need to be considered and, whenever possible, patients should be empowered in the therapeutic decisions.</p></span>" "pdfFichero" => "main.pdf" "tienePdf" => true "NotaPie" => array:1 [ 0 => array:2 [ "etiqueta" => "☆" "nota" => "<p class="elsevierStyleNotepara" id="npar0005">Please cite this article as: Grau Amorós J. ¿Es el hierro oral siempre la mejor opción?. Rev Clin Esp. 2019. <span class="elsevierStyleInterRef" id="intr0005" href="https://doi.org/10.1016/j.rce.2019.11.002">https://doi.org/10.1016/j.rce.2019.11.002</span></p>" ] ] "bibliografia" => array:2 [ "titulo" => "References" "seccion" => array:1 [ 0 => array:2 [ "identificador" => "bibs0015" "bibliografiaReferencia" => array:14 [ 0 => array:3 [ "identificador" => "bib0075" "etiqueta" => "1" "referencia" => array:1 [ 0 => array:1 [ "referenciaCompleta" => "López MAN. Hierro e insuficiencia cardiaca. DOI:10.1016/j.rce.2019.06.011." ] ] ] 1 => array:3 [ "identificador" => "bib0080" "etiqueta" => "2" "referencia" => array:1 [ 0 => array:1 [ "referenciaCompleta" => "García Erce JA, Altés A, López Rubio M, Remacha AF. 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| 2023 March | 2 | 4 | 6 |
| 2020 May | 1 | 2 | 3 |
