The Efficacy and Safety of Ferric Carboxymaltose in Heart Failure with Reduced Ejection Fraction and Iron Deficiency: An Updated Systematic Review and Meta-Analysis of Randomized Controlled Trials

<b>Background:</b> Iron deficiency (ID) often coexists with heart failure (HF), and its prevalence increases with the severity of HF. Intravenous ferric carboxymaltose (FCM) has been associated with improvements in clinical outcomes, functional capacity, and quality of life (QoL) in pati...

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Main Authors: Inderbir Padda, Sneha Annie Sebastian, Daniel Fabian, Yashendra Sethi, Gurpreet Johal
Format: Article
Language:English
Published: MDPI AG 2024-12-01
Series:Diseases
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Online Access:https://www.mdpi.com/2079-9721/12/12/339
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author Inderbir Padda
Sneha Annie Sebastian
Daniel Fabian
Yashendra Sethi
Gurpreet Johal
author_facet Inderbir Padda
Sneha Annie Sebastian
Daniel Fabian
Yashendra Sethi
Gurpreet Johal
author_sort Inderbir Padda
collection DOAJ
description <b>Background:</b> Iron deficiency (ID) often coexists with heart failure (HF), and its prevalence increases with the severity of HF. Intravenous ferric carboxymaltose (FCM) has been associated with improvements in clinical outcomes, functional capacity, and quality of life (QoL) in patients with HF and ID. However, while earlier studies showed favorable results, more recent studies have failed to demonstrate significant improvements in outcomes for patients with heart failure with reduced ejection fraction (HFrEF) and ID. This meta-analysis seeks to provide updated insights into the effectiveness and safety of FCM compared to placebo/standard of care (SoC) among patients with HFrEF and ID/iron deficiency anemia (IDA). <b>Methods:</b> We performed a systematic review and meta-analysis of the literature from inception to December 2023, utilizing databases such as MEDLINE (via PubMed), Google Scholar, the Cochrane Library, ClinicalTrials.gov, and the ScienceDirect portal. A statistical analysis was carried out using RevMan 5.4 with a random-effects model. Dichotomous outcomes were reported as odds ratios (OR), while continuous outcomes were presented as the weighted mean difference (WMD) with corresponding 95% confidence intervals (CI), and heterogeneity was assessed using the <i>I</i><sup>2</sup> test. <b>Results:</b> The final analysis included data from six randomized controlled trials (RCTs), comprising 5132 patients. Our findings indicate a significant reduction in total HF hospitalizations among patients with HFrEF and ID/IDA treated with FCM compared to those receiving the placebo or SoC, with an OR of 0.59 (95% CI: 0.40 to 0.88, <i>p</i> < 0.010). However, no statistically significant difference was observed in the total number of deaths between the FCM and placebo/SoC groups (OR: 0.85; 95% CI: 0.70 to 1.03, <i>p</i> = 0.09), non-HF hospitalizations (OR: 0.71; 95% CI: 0.41 to 1.25, <i>p</i> = 0.24), or the composite outcome of cardiovascular hospitalizations and cardiovascular deaths (OR: 0.65; 95% CI: 0.40 to 1.04, <i>p</i> = 0.07). Regarding functional capacity, as assessed by the change in 6-min walk test (6MWT) distance, no significant improvement was found, with a weighted mean difference (WMD) of 14.03 (95% CI: −10.94 to 38.99, <i>p</i> = 0.27). QoL, measured by the Kansas City Cardiomyopathy Questionnaire (KCCQ) score, also did not show significant enhancement, with a WMD of 3.85 (95% CI: −0.55 to 8.24, <i>p</i> = 0.09). Furthermore, the safety analysis revealed no significant difference in the incidence of serious adverse events between the FCM and placebo/SoC groups, with an OR of 0.73 (95% CI: 0.49 to 1.10, <i>p</i> = 0.13). <b>Conclusions:</b> In patients with HFrEF and IDA, treatment with intravenous FCM significantly lowers the risk of total HF hospitalizations but does not appear to affect functional capacity, QoL, or mortality.
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spelling doaj-art-d5b5f9bd8b7b4c3187c6c17a4b2c9c192025-08-20T02:43:29ZengMDPI AGDiseases2079-97212024-12-01121233910.3390/diseases12120339The Efficacy and Safety of Ferric Carboxymaltose in Heart Failure with Reduced Ejection Fraction and Iron Deficiency: An Updated Systematic Review and Meta-Analysis of Randomized Controlled TrialsInderbir Padda0Sneha Annie Sebastian1Daniel Fabian2Yashendra Sethi3Gurpreet Johal4Department of Internal Medicine, Richmond University Medical Center/Mount Sinai, Staten Island, NY 10310, USADepartment of Internal Medicine, Azeezia Medical College, Kollam 691537, IndiaDepartment of Internal Medicine, Richmond University Medical Center/Mount Sinai, Staten Island, NY 10310, USAPearResearch, Dehradun 248001, IndiaDepartment of Cardiology, Valley Medical Center, University of Washington, Seattle, WA 98055, USA<b>Background:</b> Iron deficiency (ID) often coexists with heart failure (HF), and its prevalence increases with the severity of HF. Intravenous ferric carboxymaltose (FCM) has been associated with improvements in clinical outcomes, functional capacity, and quality of life (QoL) in patients with HF and ID. However, while earlier studies showed favorable results, more recent studies have failed to demonstrate significant improvements in outcomes for patients with heart failure with reduced ejection fraction (HFrEF) and ID. This meta-analysis seeks to provide updated insights into the effectiveness and safety of FCM compared to placebo/standard of care (SoC) among patients with HFrEF and ID/iron deficiency anemia (IDA). <b>Methods:</b> We performed a systematic review and meta-analysis of the literature from inception to December 2023, utilizing databases such as MEDLINE (via PubMed), Google Scholar, the Cochrane Library, ClinicalTrials.gov, and the ScienceDirect portal. A statistical analysis was carried out using RevMan 5.4 with a random-effects model. Dichotomous outcomes were reported as odds ratios (OR), while continuous outcomes were presented as the weighted mean difference (WMD) with corresponding 95% confidence intervals (CI), and heterogeneity was assessed using the <i>I</i><sup>2</sup> test. <b>Results:</b> The final analysis included data from six randomized controlled trials (RCTs), comprising 5132 patients. Our findings indicate a significant reduction in total HF hospitalizations among patients with HFrEF and ID/IDA treated with FCM compared to those receiving the placebo or SoC, with an OR of 0.59 (95% CI: 0.40 to 0.88, <i>p</i> < 0.010). However, no statistically significant difference was observed in the total number of deaths between the FCM and placebo/SoC groups (OR: 0.85; 95% CI: 0.70 to 1.03, <i>p</i> = 0.09), non-HF hospitalizations (OR: 0.71; 95% CI: 0.41 to 1.25, <i>p</i> = 0.24), or the composite outcome of cardiovascular hospitalizations and cardiovascular deaths (OR: 0.65; 95% CI: 0.40 to 1.04, <i>p</i> = 0.07). Regarding functional capacity, as assessed by the change in 6-min walk test (6MWT) distance, no significant improvement was found, with a weighted mean difference (WMD) of 14.03 (95% CI: −10.94 to 38.99, <i>p</i> = 0.27). QoL, measured by the Kansas City Cardiomyopathy Questionnaire (KCCQ) score, also did not show significant enhancement, with a WMD of 3.85 (95% CI: −0.55 to 8.24, <i>p</i> = 0.09). Furthermore, the safety analysis revealed no significant difference in the incidence of serious adverse events between the FCM and placebo/SoC groups, with an OR of 0.73 (95% CI: 0.49 to 1.10, <i>p</i> = 0.13). <b>Conclusions:</b> In patients with HFrEF and IDA, treatment with intravenous FCM significantly lowers the risk of total HF hospitalizations but does not appear to affect functional capacity, QoL, or mortality.https://www.mdpi.com/2079-9721/12/12/339HFrEFiron deficiency/iron deficiency anemiaferric carboxymaltose
spellingShingle Inderbir Padda
Sneha Annie Sebastian
Daniel Fabian
Yashendra Sethi
Gurpreet Johal
The Efficacy and Safety of Ferric Carboxymaltose in Heart Failure with Reduced Ejection Fraction and Iron Deficiency: An Updated Systematic Review and Meta-Analysis of Randomized Controlled Trials
Diseases
HFrEF
iron deficiency/iron deficiency anemia
ferric carboxymaltose
title The Efficacy and Safety of Ferric Carboxymaltose in Heart Failure with Reduced Ejection Fraction and Iron Deficiency: An Updated Systematic Review and Meta-Analysis of Randomized Controlled Trials
title_full The Efficacy and Safety of Ferric Carboxymaltose in Heart Failure with Reduced Ejection Fraction and Iron Deficiency: An Updated Systematic Review and Meta-Analysis of Randomized Controlled Trials
title_fullStr The Efficacy and Safety of Ferric Carboxymaltose in Heart Failure with Reduced Ejection Fraction and Iron Deficiency: An Updated Systematic Review and Meta-Analysis of Randomized Controlled Trials
title_full_unstemmed The Efficacy and Safety of Ferric Carboxymaltose in Heart Failure with Reduced Ejection Fraction and Iron Deficiency: An Updated Systematic Review and Meta-Analysis of Randomized Controlled Trials
title_short The Efficacy and Safety of Ferric Carboxymaltose in Heart Failure with Reduced Ejection Fraction and Iron Deficiency: An Updated Systematic Review and Meta-Analysis of Randomized Controlled Trials
title_sort efficacy and safety of ferric carboxymaltose in heart failure with reduced ejection fraction and iron deficiency an updated systematic review and meta analysis of randomized controlled trials
topic HFrEF
iron deficiency/iron deficiency anemia
ferric carboxymaltose
url https://www.mdpi.com/2079-9721/12/12/339
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