Efficacy of intravenous and oral iron replacement therapies in heart failure: a network meta-analysis

Abstract Background/Introduction Iron deficiency is a common comorbidity in heart failure and is associated with worsened clinical outcomes, including reduced exercise capacity, increased hospitalisation rates, and poorer prognosis. While both oral and intravenous iron therapies are used to address this deficiency, their comparative effectiveness on biochemical and clinical parameters in heart failure remains unclear. Purpose This study aims to evaluate and compare the efficacy of various oral and intravenous iron therapies in heart failure patients, focusing on their impact on iron biochemical markers, functional capacity, and clinical outcomes. Methods A network meta-analysis was performed, assessing the impact of different iron therapies on ferritin, transferrin saturation, 6-minute walk test (6MWT), heart-failure-related hospitalisations, and all-cause mortality. Results A total of sixteen RCTs involving 6908 patients were included. Participants had a mean age range of 52.9–72.5 years, predominantly male and Caucasian. Intravenous iron formulations, particularly ferric carboxymaltose (MD 209.92, 95% CI 115.56–304.28), iron isomaltoside (MD 304.60, 95% CI 121.82–487.38), and iron sucrose (MD 225.30, 95% CI 55.09–395.51), significantly increased ferritin levels compared to placebo, whereas oral iron showed no significant effect. All therapies, except oral iron polysaccharide, significantly increased transferrin saturation (ferric carboxymaltose MD 10.00, 95% CI 9.81–10.19; iron sucrose MD 10.00, 95% CI 2.91–17.09; iron isomaltoside MD 8.00, 95% CI 3.21–12.79; oral ferrous sulphate MD 8.00, 95% CI 2.39–13.61). Intravenous ferric carboxymaltose significantly improved 6MWT distance (MD 39.07, 95% CI 13.38–64.76) and reduced heart failure-related hospitalisations (RR 0.74, 95% CI 0.57–0.96). No other formulation demonstrated these benefits. None of the iron therapies significantly reduced all-cause mortality. Conclusion(s) Intravenous iron, particularly ferric carboxymaltose, is superior to oral iron in improving iron biochemical markers, functional capacity, and reducing hospitalisation risk in heart failure patients. Further direct comparisons between intravenous formulations are needed to optimise treatment strategies.