CLINICAL QUESTION: Does IV iron reduce the risk of heart failure (HF) hospitalization and/or cardiovascular mortality in patients with systolic heart failure (EF <50%) and iron deficiency?
BACKGROUND: The American College of Cardiology and the American Heart Association recommend IV iron replacement to improve functional status and quality of life in patients with systolic heart failure and iron deficiency with or without anemia (grade 2a), but uncertainty has remained about the impact of IV iron on HF hospitalization and mortality.
STUDY DESIGN: Systematic review and meta-analysis
SETTING: A meta-analysis of six randomized trials conducted in Europe and the U.S.
SYNOPSIS: This Bayesian meta-analysis included 7,175 patients with iron deficiency and systolic heart failure (EF <50%) across six clinical trials. Patients were randomized to IV iron or standard of care, and the authors analyzed the composite outcome of cardiovascular mortality and HF admission. A significant effect was identified in the treatment group at 12 months (risk ratio [RR] 0.72; 95% confidence interval [CI] 0.55 to 0.89), and it remained significant over the duration of follow-up (RR, 0.81; 95% CI, 0.55 to 0.89). The treatment also showed a significant effect on HF admissions alone (RR, 0.69; 95% CI, 0.48 to 0.88), and both effects were robust to several sensitivity analyses.
There was no significant effect on overall or cardiovascular mortality, and there was no difference in adverse events between the study groups. Subgroup analysis did show heterogeneity of the treatment effect across gender, with no significant benefit noted among women (RR, 0.98; 95% CI, 0.75 to 1.26). The meta-analysis was slightly limited by heterogeneity in the dose and formulation of the IV iron treatment among the several trials.
BOTTOM LINE: IV iron therapy in patients with systolic heart failure (EF <50%) and iron deficiency significantly reduces the risk of HF hospitalizations.
CITATION: Anker SD, et al. Systematic review and meta-analysis of intravenous iron therapy for patients with heart failure and iron deficiency. Nat Med. 2025;31(8):2640-2646. doi: 10.1038/s41591-025-03671-1.
Dr. Graham
Dr. Culver
Dr. Graham is a med-peds hospitalist in the departments of internal medicine and pediatrics at The Ohio State University Wexner Medical Center and Nationwide Children’s Hospital, and an assistant professor of medicine at The Ohio State University College of Medicine, all in Columbus, Ohio. Dr. Culver is a hospitalist in the department of internal medicine at The Ohio State University Wexner Medical Center and an assistant professor of medicine at The Ohio State University College of Medicine, both in Columbus, Ohio.