Compared with placebo in the HEART-FID trial, ferric carboxymaltose did not improve 12-month outcomes among 3,065 patients who had heart failure with a reduced ejection fraction and iron deficiency. The primary outcome was a hierarchical composite of death, hospitalizations for heart failure, or change in 6-minute walk distance from baseline to 6 months.
Ambulatory patients with heart failure, a left ventricular ejection fraction of 40% or less, and iron deficiency were randomized to intravenous ferric carboxymaltose or placebo, in addition to standard therapy for heart failure. Doses were administered every 6 months as needed based on iron indices and hemoglobin levels. “Death by month 12 occurred in 131 patients (8.6%) in the ferric carboxymaltose group and 158 (10.3%) in the placebo group; a total of 297 and 332 hospitalizations for heart failure, respectively, occurred by month 12; and the mean (± SD) change from baseline to 6 months in the 6-minute walk distance was 8 ± 60 and 4 ± 59 m, respectively (Wilcoxon–Mann–Whitney P = 0.02; unmatched win ratio, 1.10; 99% confidence interval, 0.99 to 1.23). Repeated dosing of ferric carboxymaltose appeared to be safe with an acceptable adverse-event profile in the majority of patients. The number of patients with serious adverse events occurring during the treatment period was similar in the two groups (413 patients [27.0%] in the ferric carboxymaltose group and 401 [26.2%] in the placebo group).”
Editorial: “The transferrin saturation at baseline was relatively high in the HEART-FID trial, and in both trial groups the transferrin saturation at year 1 of follow-up was nearly identical to the value at baseline,” editorialists write. “The subgroup analysis of patients with a ferritin level of less than 100 ng per milliliter … is insufficient to explore this interaction because the subgroup consisted of both patients with a transferrin saturation of at least 20% and those with a transferrin saturation below 20%. Future analyses — preferably a meta-analysis of individual-patient data from all intravenous iron trials — should assess the importance of the transferrin saturation value at baseline. This could help redefine the definition of iron deficiency in patients with heart failure and, we hope, help clinicians determine which patients might benefit from intravenous iron supplementation.”