Renal function–dependent effects of ferric derisomaltose in heart failure

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Created On: 01/11/2025

In patients with heart failure (HF) and iron deficiency (ID), the benefit of intravenous iron may differ depending on kidney function.

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Key take away

In heart failure patients with iron deficiency, those with eGFR <45 mL/min/1.73 m² experience greater symptomatic and clinical benefit from intravenous ferric derisomaltose.

Background

In patients with heart failure (HF) and iron deficiency (ID), the benefit of intravenous iron may differ depending on kidney function. This study sought to explore the impact of ferric derisomaltose in heart failure along with iron deficiency as per the kidney function.

Method

The IRONMAN trial was a randomized, open-label study comparing intravenous ferric derisomaltose (FDI) with usual care in HF patients with left ventricular ejection fraction ≤45% and ID (transferrin saturation <20% and/or ferritin <100 µg/L). The key endpoint was a composite of recurrent HF hospitalizations and cardiovascular (CV) death, which was lower in patients receiving FDI. The outcomes were examined as per the baseline estimated glomerular filtration rate (eGFR), divided into three categories.

Result

Among 1,137 participants, 435 (38%) had eGFR <45 mL/min/1.73 m², 295 (26%) had eGFR 45–59 mL/min/1.73 m², and 407 (36%) had eGFR >60 mL/min/1.73 m². Those with eGFR <45 mL/min/1.73 m² were older, had more severe HF, and experienced more events. The rates of the primary endpoint per 100 patient-years for FDI versus usual care were 164 vs. 213 (rate ratio 0.77), 84 vs. 105 (RR 0.79), and 88 vs. 93 (RR 0.98) across the three eGFR categories, with no significant interaction between eGFR and treatment effect (p_interaction = 0.67).

In those with eGFR <45 mL/min/1.73 m², FDI improved the 4-month Minnesota Living with Heart Failure score (p_interaction = 0.01) and exhibited trends toward reducing first HF hospitalization or CV death (HR 0.76, p_interaction = 0.53) and combined outcomes of myocardial infarction, stroke, HF hospitalization, or CV death (HR 0.71, 95, p_interaction = 0.29), although interaction tests were not prominent.

Conclusion

HF patients with ID and eGFR <45 mL/min/1.73 m² tend to be more symptomatic, have poorer outcomes, and may benefit more from FDI. More studies, ideally individual patient data meta-analyses, are warranted to corroborate these outcomes.