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Meta-Analysis
. 2021 Aug;110(8):1299-1307.
doi: 10.1007/s00392-021-01837-8. Epub 2021 Mar 23.

Intravenous iron for heart failure with evidence of iron deficiency: a meta-analysis of randomised trials

Fraser J Graham  1 , Pierpaolo Pellicori  2 , Ian Ford  2 , Mark C Petrie  3 , Paul R Kalra  4 , John G F Cleland  2
Affiliations
Meta-Analysis

Intravenous iron for heart failure with evidence of iron deficiency: a meta-analysis of randomised trials

Fraser J Graham et al. Clin Res Cardiol. 2021 Aug.

Abstract

Background: The recent AFFIRM-AHF trial assessing the effect of intravenous (IV) iron on outcomes in patients hospitalised with worsening heart failure who had iron deficiency (ID) narrowly missed its primary efficacy endpoint of recurrent hospitalisations for heart failure (HHF) or cardiovascular (CV) death. We conducted a meta-analysis to determine whether these results were consistent with previous trials.

Methods: We searched for randomised trials of patients with heart failure investigating the effect of IV iron vs placebo/control groups that reported HHF and CV mortality from 1st January 2000 to 5th December 2020. Seven trials were identified and included in this analysis. A fixed effect model was applied to assess the effects of IV iron on the composite of first HHF or CV mortality and individual components of these.

Results: Altogether, 2,166 patients were included (n = 1168 assigned to IV iron; n = 998 assigned to control). IV iron reduced the composite of HHF or CV mortality substantially [OR 0.73; (95% confidence interval 0.59-0.90); p = 0.003]. Outcomes were consistent for the pooled trials prior to AFFIRM-AHF. Whereas first HHF were reduced substantially [OR 0.67; (0.54-0.85); p = 0.0007], the effect on CV mortality was uncertain but appeared smaller [OR 0.89; (0.66-1.21); p = 0.47].

Conclusion: Administration of IV iron to patients with heart failure and ID reduces the risk of the composite outcome of first heart failure hospitalisation or cardiovascular mortality, but this outcome may be driven predominantly by an effect on HHF. At least three more substantial trials of intravenous iron are underway.

Keywords: Heart failure; Intravenous iron; Iron deficiency; Meta-analysis.

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Conflict of interest statement

FG reports receipt of sponsorship from Vifor to attend an international meeting. JGFC reports receipt of personal honoraria for lectures and advisory boards from Pharmacosmos and Vifor, and from AstraZeneca, Amgen, Bayer, Novartis and Servier. IF reports receipt of research grants from Vifor and Pharmacosmos. MCP reports receipts for Consultancy and/or Endpoint Committees for Boehringer Ingleheim, Novartis, AstraZeneca, Novo Nordisk, Abbvie, Bayer, Takeda, Cardiorentis and Pharmacosmos. MCP and JGFC are supported by the British Heart Foundation (BHF) Centre of Research Excellence Award (RE/13/5/30177 and RE/18/6/34217 +). PRK reports receipt of personal honoraria for lectures, advisory boards and research/quality improvement grants from Pharmacosmos and Vifor. PRK reports receipt of personal honoraria for lectures and advisory boards from Ackea, Amgen, AstraZeneca, Bayer and Servier.

Figures

Fig. 1
Fig. 1
PRISMA diagram detailing the number of records identified, screened, included, and excluded, with a summary of the reasons for exclusion. Modified from Moher D, Liberati A, Tetzlaff J, Altman DG, The PRISMA Group (2009). Preferred Reporting Items for Systematic Reviews and Meta-Analyses: the PRISMA statement. PLoS Med 6(7): e1000097. 10.1371/journal.pmed1000097. ID iron deficiency, HHF hospitalisation for heart failure, CV cardiovascular
Fig. 2
Fig. 2
Fixed-effects meta-analysis model of all included trials detailing the pooled effect of intravenous iron on the composite of first hospitalisations for heart failure or cardiovascular mortality (a), and first hospitalisation for heart failure (b) and cardiovascular mortality (c) alone. IV intravenous, CI confidence interval
Fig. 3
Fig. 3
Fixed-effects meta-analysis model of all trials, excluding AFFIRM-AHF, detailing the pooled effect of intravenous iron on the composite of first hospitalisations for heart failure or cardiovascular mortality (a), and first hospitalisation for heart failure (b) and cardiovascular mortality (c) alone. Although not included in the pooled analysis, odds ratios and 95% confidence intervals are presented for AFFIRM-AHF for comparison. IV intravenous, CI confidence interval
See this image and copyright information in PMC

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