Treating Iron Deficiency in Heart Failure

This editorial analyzes the HEART-FID trial evaluating intravenous ferric carboxymaltose in 3065 symptomatic ambulatory patients with heart failure with reduced ejection fraction (≤40%) and iron deficiency. The primary endpoint, a hierarchical composite of death, hospitalization for heart failure, and change in 6-minute walk distance, showed a win ratio of 1.10 (99% CI: 0.99–1.23; P = 0.02), which did not meet the FDA threshold for statistical significance. While intravenous iron was safe, its effect on functional improvement and hospital readmission was modest, contrasting prior AFFIRM-AHF and IRONMAN trials. Editorial authors suggest HEART-FID’s lower-risk population and elevated baseline transferrin saturation (mean: 23.9%) may explain attenuated benefit, as prior studies showed stronger effect in those with lower transferrin saturation. They propose redefining iron deficiency thresholds in heart failure and call for a meta-analysis using individual-patient data to identify responders.

This editorial analyzes the HEART-FID trial evaluating intravenous ferric carboxymaltose in 3065 symptomatic ambulatory patients with heart failure with reduced ejection fraction (≤40%) and iron deficiency. The primary endpoint, a hierarchical composite of death, hospitalization for heart failure, and change in 6-minute walk distance, showed a win ratio of 1.10 (99% CI: 0.99–1.23; P = 0.02), which did not meet the FDA threshold for statistical significance. While intravenous iron was safe, its effect on functional improvement and hospital readmission was modest, contrasting prior AFFIRM-AHF and IRONMAN trials. Editorial authors suggest HEART-FID’s lower-risk population and elevated baseline transferrin saturation (mean: 23.9%) may explain attenuated benefit, as prior studies showed stronger effect in those with lower transferrin saturation. They propose redefining iron deficiency thresholds in heart failure and call for a meta-analysis using individual-patient data to identify responders.