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Systematic review and meta-analysis of intravenous iron therapy for patients with heart failure and iron deficiency.

Publication ,  Journal Article
Anker, SD; Karakas, M; Mentz, RJ; Ponikowski, P; Butler, J; Khan, MS; Talha, KM; Kalra, PR; Hernandez, AF; Mulder, H; Rockhold, FW; Placzek, M ...
Published in: Nat Med
August 2025

Uncertainty remains about the effect of intravenous (i.v.) iron on outcomes for heart failure (HF) with iron deficiency. In the present study, we summarize the efficacy and safety of i.v. iron from six trials (FAIR-HF, CONFIRM-HF, AFFIRM-AHF, IRONMAN, HEART-FID and FAIR-HF2), including 7,175 patients. In comparison to prior analyses, this meta-analysis added new data from FAIR-HF2, used a harmonized and robust Bayesian approach and included individual participant data from five trials. Patients assigned to i.v. iron, compared with those assigned to placebo, had lower rates for the composite endpoint of recurrent HF hospitalizations and cardiovascular mortality at 12 months (risk ratio (RR) = 0.72 (95% confidence interval (CI) = 0.55-0.89)) and for the complete length of follow-up (RR = 0.81 (95% CI = 0.63-0.97)). Each component of the primary endpoint contributed to the beneficial effect of i.v. iron at both 12 months and the complete length of follow-up: recurrent HF hospitalizations (RR = 0.69 (95% CI = 0.48-0.88) and RR = 0.78 (95% CI = 0.55-0.98), respectively) and cardiovascular mortality (hazard ratio (HR) = 0.80 (95% CI = 0.61-1.03) and HR = 0.87 (95% CI = 0.73-1.04), respectively). All-cause mortality at 12 months and for the complete length of follow-up (HR = 0.82 (95% CI = 0.65-1.03)) and HR = 0.92 (95% CI = 0.80-1.07), respectively, indicated the overall safety of i.v. iron treatment. Treatment effects were greatest in the first year after randomization when the doses of i.v. iron provided are highest. These findings suggest that treating iron deficiency in patients with HF significantly reduces cardiovascular events and also suggests further investigation of optimal dosing of i.v. iron.

Duke Scholars

Published In

Nat Med

DOI

EISSN

1546-170X

Publication Date

August 2025

Volume

31

Issue

8

Start / End Page

2640 / 2646

Location

United States

Related Subject Headings

  • Treatment Outcome
  • Randomized Controlled Trials as Topic
  • Iron Deficiencies
  • Iron
  • Immunology
  • Humans
  • Hospitalization
  • Heart Failure
  • Anemia, Iron-Deficiency
  • Administration, Intravenous
 

Citation

APA
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MLA
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Anker, S. D., Karakas, M., Mentz, R. J., Ponikowski, P., Butler, J., Khan, M. S., … Friede, T. (2025). Systematic review and meta-analysis of intravenous iron therapy for patients with heart failure and iron deficiency. Nat Med, 31(8), 2640–2646. https://doi.org/10.1038/s41591-025-03671-1
Anker, Stefan D., Mahir Karakas, Robert J. Mentz, Piotr Ponikowski, Javed Butler, Muhammad Shahzeb Khan, Khawaja M. Talha, et al. “Systematic review and meta-analysis of intravenous iron therapy for patients with heart failure and iron deficiency.Nat Med 31, no. 8 (August 2025): 2640–46. https://doi.org/10.1038/s41591-025-03671-1.
Anker SD, Karakas M, Mentz RJ, Ponikowski P, Butler J, Khan MS, et al. Systematic review and meta-analysis of intravenous iron therapy for patients with heart failure and iron deficiency. Nat Med. 2025 Aug;31(8):2640–6.
Anker, Stefan D., et al. “Systematic review and meta-analysis of intravenous iron therapy for patients with heart failure and iron deficiency.Nat Med, vol. 31, no. 8, Aug. 2025, pp. 2640–46. Pubmed, doi:10.1038/s41591-025-03671-1.
Anker SD, Karakas M, Mentz RJ, Ponikowski P, Butler J, Khan MS, Talha KM, Kalra PR, Hernandez AF, Mulder H, Rockhold FW, Placzek M, Röver C, Cleland JGF, Friede T. Systematic review and meta-analysis of intravenous iron therapy for patients with heart failure and iron deficiency. Nat Med. 2025 Aug;31(8):2640–2646.

Published In

Nat Med

DOI

EISSN

1546-170X

Publication Date

August 2025

Volume

31

Issue

8

Start / End Page

2640 / 2646

Location

United States

Related Subject Headings

  • Treatment Outcome
  • Randomized Controlled Trials as Topic
  • Iron Deficiencies
  • Iron
  • Immunology
  • Humans
  • Hospitalization
  • Heart Failure
  • Anemia, Iron-Deficiency
  • Administration, Intravenous