IV Iron Therapy Cuts Cardiovascular Events in Heart Failure with Iron Deficiency, New Meta-Analysis Reveals

The meta-analysis, which included 7,175 HF patients, demonstrated that IV iron therapy significantly reduced cardiovascular events compared to placebo. Patients receiving IV iron experienced fewer recurrent heart failure hospitalizations and lower cardiovascular mortality, with a relative risk (RR) of 0.72 at 12 months and 0.81 over the entire follow-up period. Importantly, the therapy was safe, showing no increase in all-cause mortality.

The researchers note that uncertainty persists regarding the effect of intravenous (IV) iron on outcomes in heart failure (HF) with iron deficiency. To address this, Stefan D. Anker, Deutsches Herzzentrum der Charité, Campus Virchow Klinikum, Berlin, Germany, and colleagues summarize the efficacy and safety of IV iron based on data from six trials—FAIR-HF, CONFIRM-HF, AFFIRM-AHF, IRONMAN, HEART-FID, and FAIR-HF2—encompassing 7,175 patients.

This meta-analysis offers several advancements over previous analyses, incorporating new data from the FAIR-HF2 trial and utilizing a robust Bayesian approach. Additionally, it includes individual participant data from five of the trials, providing a more detailed and harmonized evaluation of IV iron's effects.

The study revealed the following findings:

• Patients receiving IV iron had lower rates of recurrent heart failure hospitalizations and cardiovascular deaths compared to those on a placebo, both at 12 months and throughout the follow-up period.
• The risk reduction for recurrent heart failure hospitalizations was 31% at 12 months (RR 0.69) and 22% over the full follow-up (RR 0.78).
• For cardiovascular deaths, IV iron reduced the risk by 20% at 12 months (HR 0.80) and 13% over the entire follow-up period (HR 0.87).
• All-cause mortality also showed a trend toward safety with IV iron treatment, with an 18% risk reduction at 12 months (HR 0.82) and an 8% reduction over the full follow-up (HR 0.92).
• These results highlight the efficacy and safety of IV iron in improving outcomes for heart failure patients with iron deficiency. The treatment effects were most significant during the first year after randomization when the doses of IV iron were at their highest.

"These findings indicate that addressing iron deficiency in heart failure patients significantly reduces cardiovascular events and highlight the need for further research into the optimal dosing of intravenous iron," the researchers concluded.

Reference:

Anker, S. D., Karakas, M., Mentz, R. J., Ponikowski, P., Butler, J., Khan, M. S., Talha, K. M., Kalra, P. R., Hernandez, A. F., Mulder, H., Rockhold, F. W., Placzek, M., Röver, C., Cleland, J. G., & Friede, T. (2025). Systematic review and meta-analysis of intravenous iron therapy for patients with heart failure and iron deficiency. Nature Medicine, 1. https://doi.org/10.1038/s41591-025-03671-1