Intravenous ferric carboxymaltose in heart failure with iron deficiency (FAIR-HF2 DZHK05 trial) : sex-specific outcomes

Karakas, Mahir (author), Friede, Tim (author), Butler, Javed (author), Talha, Khawaja M. (author), Placzek, Marius (author), Asendorf, Thomas (author), Diek, Monika (author), Nosko, Anna (author), Stas, Adriane (author), Kluge, Stefan (author), Lainščak, Mitja (author)

Aims: Intravenous iron has emerged as a guideline-recommended therapy in patients with heart failure and iron deficiency, but the potential sex-related differences in efficacy are unknown. We aimed to assess sex-specific outcomes in the Intravenous Iron in Patients with Systolic Heart Failure and Iron Deficiency to Improve Morbidity & Mortality (FAIR-HF2-DZHK05) trial. Methods and results: FAIR-HF2 included 1105 heart failure patients with a left ventricular ejection fraction ≤45% and iron deficiency. A total of 368 women (mean age 68.7 ± 13.0 years) and 737 men (mean age 70.5 ± 11.0 years) were randomized to intravenous ferric carboxymaltose or placebo. The three primary endpoints were (i) time to cardiovascular death or first heart failure hospitalization, (ii) total heart failure hospitalizations, and (iii) time-to-first event of cardiovascular death or heart failure hospitalization only in patients with transferrin saturation <20% at baseline. The hazard ratio (HR) for the first primary outcome was 1.07 (95% confidence interval [CI] 0.63-1.82, p = 0.80) in women and 0.74 (95% CI 0.57-0.95, p = 0.016) in men, while the rate ratios (RRs) for the second primary outcome were 1.06 (95% CI 0.55-2.05, p = 0.86) and 0.79 (95% CI 0.58-1.08, p = 0.136), respectively, and the HRs for the third primary outcome event were 1.21 (95% CI 0.62-2.36, p = 0.58) and 0.73 (95% CI 0.55-0.97, p = 0.028), respectively. Regarding safety outcomes, the HR for all-cause mortality was 1.46 (95% CI 0.78-2.76, p = 0.24) in women, suggesting increased mortality risk under iron supplementation, in contrast to 0.86 (95% CI 0.64-1.16, p = 0.33) in men (p for interaction = 0.13). Conclusions: This analysis indicates relevant differential efficacy of intravenous iron in heart failure across both sexes. While men receiving ferric carboxymaltose experienced a clinically relevant reduction in cardiovascular death and heart failure hospitalizations, women did not derive similar benefits. The results are clinically relevant and prompt validation in other large outcome trials of intravenous iron supplementation in heart failure.

• Language: English
• Keywords: ferric carboxymaltose, heart failure, iron deficiency, randomized controlled clinical trials, sex-specific outcomes
• Work type: Article
• Typology: 1.01 - Original Scientific Article
• Organization: MF - Faculty of Medicine
• Publication status: Published
• Publication version: Version of Record
• Year: 2025
• Number of pages: Str. 2328-2342
• Numbering: Vol. 27, iss. 11
• PID: 20.500.12556/RUL-181691
• UDC: 616.1
• ISSN on article: 1388-9842
• DOI: 10.1002/ejhf.3742
• COBISS.SI-ID: 252026627
• Publication date in RUL: 13.04.2026

Record is a part of a journal

• Title: European journal of heart failure
• Shortened title: Eur. j. heart fail.
• Publisher: Wiley, European Society of Cardiology
• ISSN: 1388-9842
• COBISS.SI-ID: 1217301

Licences

• License: CC BY 4.0, Creative Commons Attribution 4.0 International
• Link: http://creativecommons.org/licenses/by/4.0/
• Description: This is the standard Creative Commons license that gives others maximum freedom to do what they want with the work as long as they credit the author.

Secondary language

• Language: Slovenian
• Keywords: železova karboksimaltoza, srčno popuščanje, pomanjkanje železa, randomizirana kontrolirana klinična preskušanja, izidi, specifični za spol