Iron deficiency is commonly seen in heart failure patients and is believed to be related to factors such as insufficient dietary intake, poor absorption, and inflammation. Ferric carboxymaltose (FCM) is an intravenous iron therapy that has been investigated for its potential benefits in heart failure patients with reduced ejection fraction (HFrEF) and iron deficiency. The HEART-FID trial aimed to determine whether FCM improves hard outcomes in this patient population.
In the HEART-FID trial, patients with HFrEF and iron deficiency were randomized to receive FCM or placebo every 6 months based on iron repletion biomarkers. The trial assessed a hierarchical efficacy composite endpoint consisting of all-cause mortality at 12 months, heart failure hospitalizations at 12 months, and change in 6-minute walk distance at 6 months. While the overall win ratio slightly favored FCM, it did not reach statistical significance. Additionally, the time to first heart failure hospitalization or cardiovascular death was similar between the FCM and placebo groups over a median follow-up of 1.9 years. The trial also found no significant difference in treatment-emergent adverse events between the two groups.
The results of the HEART-FID trial, along with other IV iron trials, suggest a possible improvement in hard outcomes with IV iron therapy but do not definitively prove its effectiveness. Previous trials, such as IRONMAN and AFFIRM-AHF, showed trends towards reduced risks of hospital admission and cardiovascular death with IV iron therapy but did not reach statistical significance. While the totality of evidence from these studies suggests safety and potential benefits of IV iron therapy in HFrEF with iron deficiency, further research is needed to fully understand its efficacy.
A meta-analysis presented at the same conference confirmed the narrow miss for IV iron therapy in preventing heart failure hospitalizations and cardiovascular death at 12 months. The analysis included data from HEART-FID, CONFIRM-HF, and AFFIRM-AHF trials and identified potential predictors of treatment benefit, such as higher transferrin saturation (TSAT) and cumulative iron dosing. The timing of iron re-dosing was also highlighted as an area for reconsideration, suggesting that the current biomarker-based approach may not be optimal.
Edward Fry, MD, an expert in the field, acknowledges that while the HEART-FID trial did not meet its primary endpoint, iron supplementation is already recommended in guidelines and is likely to continue being used in practice. Scott Solomon, MD, another expert, discusses the modest benefit observed in the trial, particularly in the 6-minute walk distance, and highlights the disappointment in traditional hard endpoints like time to cardiovascular death or first heart failure hospitalization.
Several limitations of the HEART-FID trial were identified, including drug interruptions and IV iron drop-ins despite the study being well-powered. These limitations may have influenced the results and should be considered when interpreting the findings.
The HEART-FID trial provides valuable insights into the potential benefits of intravenous iron therapy in HFrEF patients with iron deficiency. While the trial did not demonstrate a significant improvement in hard outcomes, it contributes to the growing body of evidence suggesting the safety and potential benefits of IV iron therapy in this patient population. Further research is needed to identify subgroups of patients who may benefit the most from IV iron therapy and to refine the timing and dosing strategies. In the meantime, the use of IV iron therapy for improving functional status and quality of life in heart failure patients remains a reasonable option.