A recent study presented at the American College of Cardiology’s Annual Scientific Session (ACC.25) investigated the effects of intravenous iron supplementation on patients with heart failure with reduced ejection fraction (HFrEF). While the primary endpoints related to cardiovascular events did not reach statistical significance, the findings suggest a notable reduction in cardiovascular death or heart failure hospitalization by approximately 20% in those receiving iron therapy. Additionally, improvements were observed in secondary outcomes such as quality of life during the first year when the dosage was highest.

These results align with previous studies and meta-analyses involving over 7,000 HFrEF patients, confirming that intravenous iron is beneficial for symptom relief and reducing cardiovascular events, particularly within the first year of treatment. The trial also highlighted the importance of understanding gender-specific differences in cardiovascular benefits and emphasized the need for further research into its application for heart failure with preserved ejection fraction (HFpEF).

Efficacy of Intravenous Iron Supplementation

The FAIR-HF2 trial demonstrated mixed but promising outcomes regarding intravenous iron supplementation for HFrEF patients. Although the primary endpoints concerning cardiovascular events were not statistically significant, a trend toward improved outcomes was evident, especially in the first year when higher doses were administered. Patients experienced a 21% lower risk of cardiovascular death or first heart failure hospitalization overall. However, this difference diminished over time due to variations in the amount of iron received annually.

This decline in effectiveness after the initial year can be attributed to the decreasing dosages of iron administered subsequently. During the first year, participants received an average total of 2,040 mg of iron, which gradually decreased in subsequent years. This pattern suggests that the therapeutic benefits of intravenous iron are closely tied to the dosage levels. Lead researcher Stefan D. Anker noted that these findings underscore the importance of administering higher doses initially for optimal results. Furthermore, the meta-analysis revealed consistent patterns indicating that the first year of therapy is crucial for maximizing benefits. Future research should explore strategies to maintain efficacy beyond the first year.

Patient Outcomes and Safety Profile

Beyond cardiovascular event rates, intravenous iron supplementation significantly enhanced the quality of life for HFrEF patients. Questionnaires assessing health-related quality of life and perceived well-being revealed marked improvements among those receiving iron compared to the placebo group. Despite these positive effects, safety outcomes remained comparable between groups, with no significant differences observed in all-cause mortality, cardiovascular mortality, or infections over three years.

These safety assurances reinforce the conclusion drawn by Dr. Anker that intravenous iron therapy, as administered in the FAIR-HF2 trial and similar studies, poses no increased risks to patients. Challenges faced during the trial, including disruptions from the COVID-19 pandemic and changes in international guidelines, affected follow-up procedures and duration, potentially limiting the magnitude of observed differences. Nevertheless, the consistency of findings with prior trials and meta-analyses strengthens confidence in the therapy's potential benefits. Further investigation is warranted to determine applicability for HFpEF patients and to clarify gender-specific cardiovascular advantages of intravenous iron supplementation.