IV Iron Therapy Benefits Patients With Heart Failure, Severe Anemia, and Low TSAT

Photo Credit: Inna Kharlamova

IRONMAN trial highlighted that anemia severity and TSAT < 20% are key indicators for identifying patients with heart failure who may benefit from intravenous iron therapy.

The IRONMAN trial aimed to clarify the relationship between iron deficiency, as indicated by various blood tests, and the response to intravenous iron therapy in patients with heart failure, according to research presented in the European Heart Journal. Conducted on 1,137 patients with heart failure and reduced ejection fraction (≤45%), the study investigated the impact of baseline anemia severity, serum ferritin, and transferrin saturation (TSAT) on the response to intravenous ferric derisomaltose (FDI) compared to usual care.

The study found that patients with lower baseline TSAT, lower ferritin levels, and more severe anemia showed a greater increase in hemoglobin levels following FDI administration. Specifically, the rise in hemoglobin was significantly associated with lower baseline TSAT (P<0.0001), lower ferritin (P=0.028), and more severe anemia (P=0.014). Improvements in the Minnesota Living with Heart Failure (MLwHF) score were modestly better in more anemic patients receiving FDI, particularly in the emotional domain (P=0.043), though this was not related to baseline TSAT or ferritin levels.

However, no significant difference was observed in the 6-minute walk distance between patients receiving FDI and those receiving usual care. Interestingly, patients without anemia or with TSAT ≥ 20% had lower event rates and little evidence of benefit from FDI. Conversely, those with more severe anemia or TSAT < 20%—especially when ferritin was ≥100 µg/L—experienced higher event rates and greater absolute reductions in events with FDI, though these findings were not statistically significant.

The analysis suggests that patients with heart failure who have anemia or TSAT < 20% with ferritin > 100 µg/L might derive the most benefit from intravenous iron therapy. This insight requires further validation in future studies.

Iron deficiency in patients with heart failure is often defined by low serum ferritin or low TSAT. While the WHO sets specific thresholds for iron deficiency, many clinical laboratories use different values. For instance, a serum ferritin ≤30 µg/L and TSAT < 20% are commonly accepted markers of iron deficiency. The IRONMAN trial adopted similar criteria, targeting serum ferritin < 100 µg/L or TSAT < 20%.

The trial demonstrated that intravenous iron significantly increased hemoglobin levels and improved quality of life in patients with more severe anemia. Although the effect on clinical event rates was less clear, the trend indicated potential benefits, especially in those with lower TSAT. The findings underline the importance of tailoring iron supplementation to those with clear markers of iron deficiency to optimize therapeutic outcomes.

Overall, the IRONMAN trial highlighted that anemia severity and TSAT < 20% are key indicators for identifying patients with heart failure who may benefit from intravenous iron therapy. These results, if confirmed, could refine clinical guidelines, ensuring targeted treatment and better resource utilization in managing patients with heart failure and iron deficiency.