Journal Article

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

Schiff, Rebekah, Sze, Shirley, Szwejkowski, Benjamin, Bulugahapitiya, Sudantha, Wright, Jay, Gupta, Preeti, Banerjee, Prithwish, Lang, Ninian, Labinjoh, Catherine, Ray, Robin, Keeling, Philip, Elzayat, Ahmed, Turner, Charlotte, Petrie, Mark C, Glover, Jason, Matias, Sofia, Francis, Mark, Squire, Iain, Ellery, Susan, McClure, Samuel, Baxter, John, Sankaranarayanan, Rajiv, Jenkins, Geraint, Cowburn, Peter James, Campbell, Philip, Chapman, Callum, Ahmed, Fozia, Davis, Gershan, Sobolewska, Jolanta, Lane, Rebeca, Murphy, Jerry, Kalra, Paul R, Williams, Simon, Bakhai, Ameet, Kalra, Paul, Cooke, Justin, Ford, Ian, Thomson, Elizabeth A, Matthews, Iain, Lyons, Kristopher, Duckett, Simon, Krishnamurthy, Vinodh, Kalra, Philip, Wicks, Eleanor, Cowan, Elena, Boos, Christopher J, Hussain, Ifza, Seed, Alison, Gamma, Reto, Lang, Ninian N, Cleland, John G, Wong, Aaron, Pellicori, Pierpaolo, Boos, Christopher, Robertson, Michele, Foley, Paul, Petrie, Colin, Rogers, Paula, Savage, Henry, Jackson, Thomas, Clifford, Piers, Critoph, Christopher, Marshall, Andrew, Austin, Rosalynn, Japp, Alan, Al-Mohammad, Abdallah, Leslie, Stephen, Walsh,

2025

Overview

BackgroundIntravenous 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.MethodsThe 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.ResultsAmong 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.ConclusionsWe 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.

• Publisher: BMJ Publishing Group Ltd and British Cardiovascular Society,BMJ Publishing Group LTD,BMJ Publishing Group
• Subject: Administration, Intravenous / Age Factors / Age groups / Aged / Aged, 80 and over / Anemia, Iron-Deficiency - blood / Anemia, Iron-Deficiency - complications / Anemia, Iron-Deficiency - diagnosis / Anemia, Iron-Deficiency - drug therapy / Anemia, Iron-Deficiency - mortality / Cardiac arrhythmia / Clinical outcomes / Comorbidity / Disaccharides - administration & dosage / Disaccharides - adverse effects / Ejection fraction / Female / Ferric Compounds - administration & dosage / Ferric Compounds - adverse effects / Heart failure / Heart Failure - blood / Heart Failure - complications / Heart Failure - diagnosis / Heart Failure - drug therapy / Heart Failure - mortality / Heart Failure - physiopathology / Heart Failure and Cardiomyopathies / Hemoglobin / Hemoglobins - metabolism / Hospitalization / Hospitalization - statistics & numerical data / Humans / Hypertension / Iron / Male / Maltose - administration & dosage / Maltose - adverse effects / Maltose - analogs & derivatives / Middle Aged / Original Research / Patients / Prospective Studies / Quality of Life / Questionnaires / Stroke Volume / Treatment Outcome