Study: Intravenous Iron Improves Long-Term Outcomes for Patients with Heart Failure, Iron Deficiency

New data presented at the American Heart Association 2022 Scientific Sessions has found that repeated intravenous (IV) iron administration reduced the risk of hospitalization for heart failure and cardiovascular-related death in patients with heart failure and iron deficiency.¹

Iron deficiency is common among patients with heart failure and can exacerbate low quality of life, poor ability to exercise, and higher risk of hospitalization or death, according to presenter Paul Kalra, MD. Earlier research has also shown that iron deficiency among patients with heart failure may be quickly improved with intravenous iron infusions.¹

“Despite several great therapeutic successes in recent decades, many people with heart failure still have symptoms that restrict their daily lives, and the rates of hospital admissions and mortality remain high,” Kalra said in a press release. “There is an urgent need for new treatments that are safe and affordable.”²

The Effectiveness of Intravenous Iron Treatment vs Standard Care in Patients with Heart Failure and Iron Deficiency (IRONMAN) trial was designed to investigate whether long-term administration of IV iron improved outcomes in this patient population. Iron infusions were compared with the current guideline-recommended care, which does not include IV iron administration.¹

The trial was conducted in the United Kingdom and included 1137 adult participants with heart failure and iron deficiency. Participants had an average age of 73 years and nearly three-quarters were male.¹

Participants in the trial were randomized to receive either IV iron or placebo, in addition to standard of care for heart failure. Those assigned to receive IV iron infusions also received additional doses at the 1-month review period and every 4 months after that if their iron deficiency returned. Participants were followed for a median of just over 2.5 years with follow-up clinic visits every 4 months.¹

According to the results, long-term administration of IV iron had significant benefits for patients with heart failure and iron deficiency. Over the follow-up period, intravenous iron reduced the risk of hospitalization for heart failure or cardiovascular death by approximately 20%. Patients in the IV iron arm also reported improved well-being, as assessed using heart failure-related quality-of-life questionnaires. However, this impact was found during initial assessment at 4 months and not during re-assessment at 20 months.¹

Long-term IV iron administration was not associated with a greater risk of infection. It was associated with fewer serious adverse cardiac events compared to standard of care treatments.¹

“People with heart failure are at risk of developing recurrent iron deficiency if their iron levels are not ‘topped up’ regularly,” Kalra said in the press release. “These results demonstrate that repeated dosing with intravenous iron is a beneficial, safe, and well-tolerated treatment option that may improve the well-being of adults with heart failure and iron deficiency within a few months.”²

Kalra noted that the COVID-19 pandemic limited clinicians’ ability to see patients in-person, which may have inhibited the ability to administer more IV iron as needed. This likely reduced the magnitude of benefit seen with the infusions.¹

To account for this, however, the investigators performed a further analysis of the 1063 participants who were in the trial prior to March 31, 2020, and whose treatment was not as affected by the pandemic. This analysis found a significant benefit of IV iron in reducing the risk of heart failure-related hospitalization and cardiovascular death.¹

Kalra noted some limitations of the study, including that it was not blinded due to the darker color of IV iron versus a clear saline placebo.¹ To reduce the risk of bias, investigators who reviewed and validated the trial outcomes were not aware of which treatment had been administered to which patients.²

“It is important to highlight that the beneficial results were seen despite the fact that approximately 1 in 6 patients randomized to standard care alone received intravenous iron outside the trial,” Kalra said in the press release. “This likely reduced the level of benefit seen with intravenous iron in the study.”²

REFERENCES

1. Kalra, P. IRONMAN: A Randomized Trial of Intravenous Ferric Derisomaltose in Heart Failure With Reduced Ejection Fraction. Presented at: American Heart Association 2022 Scientific Sessions. November 5, 2022.
2. Intravenous iron improved long-term outcomes for people with heart failure and iron deficiency. News release. American Heart Association; November 5, 2022. https://newsroom.heart.org/news/intravenous-iron-improved-long-term-outcomes-for-people-with-heart-failure-and-iron-deficiency