Does Treating Iron Deficiency in Heart Failure Help?

Patients with heart failure and iron deficiency treated with intravenous iron had lower rates of cardiovascular death or hospitalization for heart failure, but results of the FAIR-HF2 study failed to achieve statistical significance. However, when the study’s results are added to those of five previous trials, important benefits for patients were shown.

The FAIR-HF2 trial results were presented by investigator Stefan Anker, MD, PhD, cardiologist at Deutsches Herzzentrum der Charité in Berlin, Germany, at the American College of Cardiology Scientific Session 2025 in Chicago and published simultaneously in JAMA. The meta-analysis of the six studies was published simultaneously in Nature Medicine.

FAIR-HF2 was conducted in 70 centers in six European countries but enrolled only 1105 patients, which was not enough to show a significant effect of infusions with iron ferric carboxymaltose, Anker explained. “You need at least 2000 patients. Otherwise, trials in this area are too small.”

FAIR-HF2 Study

The double-blind placebo-controlled trial looked at the effects of intravenous iron on time to cardiovascular death, time to first hospitalization for heart failure, and total hospitalizations for heart failure. Results showed improvements in these outcomes by 20%-21%, but none was statistically significant.

The study also looked at time to cardiovascular death and time to first hospitalization for heart failure specifically in patients with a transferrin saturation < 20%, which is a stricter definition of iron deficiency. The treatment effect in these patients was similar to that in all patients, refuting the idea that patients in this group might benefit more from treatment than the wider group of patients with heart failure and iron deficiency.

To solve the problem of insufficient patients, the research team added their FAIR-HF2 data to data from five previous studies. For four of those studies, they were able to use raw data on individual participants, which made the statistical analysis more robust, Anker said.

Effects Mount With Number of Patients

With more than 7000 patients, the meta-analysis showed that intravenous iron significantly lowered the rates of cardiovascular death and recurrent hospitalization for heart failure, both separately and combined. Deaths from all causes were also significantly lower.

But the meta-analysis held a surprise for the researchers. An analysis of specific groups of patients showed that women did not benefit in terms of lower rates of death or hospitalization. “This needs further exploration,” said Anker because the reason for the discrepancy by gender is unclear.

FAIR-HF2 also showed that intravenous iron was safe for patients and improved their quality of life, he added. “Patients feel better.”

“At the end of the day, we want all our patients with heart failure to feel better, and your data support that,” said Richard Cheng, MD, a cardiologist at the University of California, San Francisco, who was not involved in the study.