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

Sze, Shirley; Squire, Iain; Kalra, Paul R; Cleland, John G; Petrie, Mark C; Kalra, Philip A; Ahmed, Fozia; Banerjee, Prithwish; Boos, Christopher J; Chapman, Callum; Cowburn, Peter James; Dixon, Lana; Duckett, Simon; Lane, Rebecca; Foley, Paul; Lang, Ninian N; Lyons, Kristopher; Ray, Robin; Schiff, Rebekah; Thomson, Elizabeth A; Robertson, Michele; Ford, Ian

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.

Citation

Sze, S., Squire, I., Kalra, P. R., Cleland, J. G., Petrie, M. C., Kalra, P. A., Ahmed, F., Banerjee, P., Boos, C. J., Chapman, C., Cowburn, P. J., Dixon, L., Duckett, S., Lane, R., Foley, P., Lang, N. N., Lyons, K., Ray, R., Schiff, R., Thomson, E. A., …Ford, I. (2025). Age-stratified effects of intravenous ferric derisomaltose in heart failure with iron deficiency: insights from the IRONMAN trial. Heart, heartjnl-2024-324908. https://doi.org/10.1136/heartjnl-2024-324908

• Journal Article Type: Article
• Acceptance Date: Jan 24, 2025
• Online Publication Date: Feb 12, 2025
• Publication Date: Feb 12, 2025
• Deposit Date: Feb 20, 2025
• Publicly Available Date: Feb 20, 2025
• Journal: Heart
• Print ISSN: 1355-6037
• Electronic ISSN: 1468-201X
• Publisher: BMJ Publishing Group
• Peer Reviewed: Peer Reviewed
• Pages: heartjnl-2024-324908
• DOI: https://doi.org/10.1136/heartjnl-2024-324908
• Keywords: heart failure
• Public URL: https://keele-repository.worktribe.com/output/1076502
• Publisher URL: https://heart.bmj.com/content/early/2025/02/11/heartjnl-2024-324908