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Randomized Controlled Trial
. 2025 Jun 13;111(13):634-641.
doi: 10.1136/heartjnl-2024-324908.

Age-stratified effects of intravenous ferric derisomaltose in heart failure with iron deficiency: insights from the IRONMAN trial

Shirley Sze  1 , Iain Squire  1 , Paul R Kalra  2 , John G Cleland  3 , Mark C Petrie  3 , Philip A Kalra  4 , Fozia Ahmed  5   6 , Prithwish Banerjee  7 , Christopher J Boos  8 , Callum Chapman  9 , Peter James Cowburn  10 , Lana Dixon  11 , Simon Duckett  12 , Rebecca Lane  13 , Paul Foley  14 , Ninian N Lang  3 , Kristopher Lyons  15 , Robin Ray  16 , Rebekah Schiff  17 , Elizabeth A Thomson  18 , Michele Robertson  18 , Ian Ford  19 ; IRONMAN Study group
Collaborators, Affiliations
Randomized Controlled Trial

Age-stratified effects of intravenous ferric derisomaltose in heart failure with iron deficiency: insights from the IRONMAN trial

Shirley Sze et al. Heart. .

Abstract

Background: Intravenous iron therapy with ferric derisomaltose (FDI) has been shown to improve outcomes in patients with heart failure with reduced ejection fraction (HFrEF) and iron deficiency. However, its effects across different age groups remain unclear. This analysis of the Effectiveness of Intravenous Iron Treatment versus Standard Care in Patients with Heart Failure and Iron Deficiency (IRONMAN) trial explored the efficacy and safety of FDI across age groups.

Methods: The IRONMAN trial was a prospective, open-label, blinded end point randomised controlled trial enrolling patients with HFrEF and iron deficiency. This prespecified analysis stratified the population into four quarters by age group: <67 years, 67-73 years, 74-79 years, >79 years. The primary outcome was a composite of recurrent heart failure hospitalisations and cardiovascular death. Secondary outcomes included changes in haemoglobin and quality of life. Clinical outcomes comparing FDI versus usual care in each age subgroup were analysed by the method of Lin et al for recurrent events and Cox proportional hazards model for time to first event. Interactions between age and treatment effects were explored.

Results: Among 1137 randomised patients (median age 73 years), the primary outcome rate ratio (FDI vs usual care) was 0.87 (95% CI 0.61 to 1.23) in patients <67 years, 0.93 (95% CI 0.66 to 1.32) in those aged 67-73 years, 0.88 (95% CI 0.59 to 1.33) in those aged 74-79 years and 0.66 (95% CI 0.45 to 0.96) in those aged >79 years (p-interaction=0.38). Improvements in haemoglobin and quality of life scores at 4 months did not differ statistically across age groups (p-interaction=0.92 and 0.64, respectively). Older patients were more symptomatic at baseline, with higher N-terminal-pro B-type natriuretic peptide levels and poorer renal function, but safety outcomes did not differ across age groups.

Conclusions: We found no evidence that the effects of FDI on heart failure hospitalisations, cardiovascular death, haemoglobin and quality of life differed by age. These findings support its use in patients with HFrEF and iron deficiency, including older adults.

Trial registration number: NCT02642562.

Keywords: heart failure.

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Conflict of interest statement

Competing interests: SS reports a research grant from British Heart Foundation. IS reports a research grant from British Heart Foundation. PRK reports research grants from British Heart Foundation and Pharmacosmos; consulting fees from Amgen, Boehringer Ingelheim, Pharmacosmos, Servier and CSL Vifor; payment for lectures from AstraZeneca, Bayer, Novartis, Pfizer, Pharmacosmos, CSL Vifor and Amgen; support for attending meetings from Pharmacosmos; is a data safety monitoring board member for the STOP-ACE trial, EMPRESS-MI; and has served as Chair of the British Society for Heart Failure. JGC reports research grants from British Heart Foundation, Pharmacosmos, Bristol Myers Squibb, CSL Vifor; consulting fees from Pharmacosmos, CSL Vifor, Biopeutics; payment for lectures from Pharmacosmos; support for attending meetings from Pharmacosmos; is a data safety monitoring board member for ADAPT-CRT, CMR Guide, PROTECT-HF; has stock with Heartfelt Limited and Viscardia. MCP reports research grants from British Heart Foundation, NIHR, Boehringer Ingelheim, Roche, SQ Innovations, AstraZeneca, Novartis, Novo Nordisk, Medtronic, Boston Scientific, Medtronic, Pharmacosmos; consulting fees from Abbott, Akero, Applied Therapeutics, Amgen, AnaCardio, Biosensors, Boehringer Ingelheim, Corteria, Novartis, AstraZeneca, Novo Nordisk, AbbVie, Bayer, Horizon Therapeutics, Foundry, Takeda, Cardiorentis, Pharmacosmos, Siemens, Eli Lilly, Vifor, New Amsterdam, Moderna, Teikoku, LIB Therapeutics, 3R Lifesciences, Reprieve, FIRE 1, Corvia, Regeneron; payment from Boehringer Ingelheim, Novartis, AstraZeneca, Novo Nordisk, Pharmacosmos, Eli Lilly, Vifor; support for attending meetings from Boehringer Ingelheim, Novartis, AstraZeneca, Novo Nordisk, Pharmacosmos, Eli Lilly, Vifor; is a data safety monitoring board or advisory board member for AstraZeneca, Teikoku and Moderna. PAK reports research grant support from Astellas, Evotec, Pharmacosmosand Vifor Pharma; consulting fees from AstraZeneca, UCB, Unicyte, and Vifor Pharma; payment for lectures from AstraZeneca, Bayer, Napp, Pfizer, Pharmacosmos and Vifor Pharma; and support for attending meetings from Pharmacosmos and Vifor Pharma. FA reports a research grant from Medtronic; consulting fees and payment for lectures, support for attending meetings and participation on a data safety monitoring board or advisory board from Abbott, AstraZeneca, Medtronic, Novo Nordisk, Pfizer, Pharmacosmos, Servier and Vifor Pharma. SD reports support for attending meetings from Pharmacosmos, British Society of Heart Failure, TAVI today and has served as Chair of British Society of Heart Failure. RL reports payment from Abbott and is a member of the Advisory Board for Abbott. PF received payment or honoraria for educational events. NNL reports research grants from AstraZeneca, Boehringer Ingelheim and Roche Diagnostics; consulting fees from Akero Therapeutics, CV6 Therapeutics, Myokardia; payment for lectures from Jazz Pharma; support for attending meetings from Pharmacosmos, and is on a data safety monitoring board or advisory board for CV6 therapeutics. RR reports consulting fees from Pharmacosmos; payment for lectures from Pharmacosmos. EAT, MR and IF report research grants from British Heart Foundation and Pharmacosmos. All other authors declare no competing interests.

Figures

Figure 1
Figure 1. Rates of recurrent heart failure hospitalisations and cardiovascular death by age group. FDI, intravenous ferric derisomaltose; RR, rate ratio.
Figure 2
Figure 2. Change in haemoglobin levels at 4 months across age groups. FDI, intravenous ferric derisomaltose; TSAT, transferrin saturation.
See this image and copyright information in PMC

References

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