Ferric carboxymaltose was not found to have a significant impact on 6-minute walk distance, which is part of the primary outcome’s hierarchical composite of death and hospitalizations from heart failure.
Ferric carboxymaltose therapy was not found to be more effective than placebo at reducing death or hospitalizations among ambulatory patients with heart failure (HF), reduced ejection fraction, and iron deficiency, according to the results from the Ferric Carboxymaltose in Heart Failure With Iron Deficiency (HEART-FID) study, which was recently published in the New England Journal of Medicine.
Investigators conducted the double-blind, randomized (1:1), placebo-controlled, and event-driven HEART-FID trial to evaluate the safety and efficacy of ferric carboxymaltose therapy forreducing HF-related death/hospitalizations within 12 months of randomization for patients with HF, reduced ejection fraction, and iron deficiency; and improving 6-minute walk distance at 6 months. Ferric carboxymaltose therapy did not significantly improve this primary outcome. Among patients in the study, 131 (8.6%) in the ferric carboxymaltose group died by month 12 compared to 158 (10.3%) patients in the placebo group. There were 297 hospitalizations among patients in the ferric carboxymaltose group compared with 332 in the placebo cohort.
“The lack of a long-term reduction in hospitalizations for HF in our trial was unexpected,” the study authors wrote in the publication.
In addition, the mean change in 6-minute walk distance was 8±60 m for the ferric carboxymaltose group and 4±59 m for the placebo group (overall P = 0.02). The study’s main secondary outcome was composite of cardiovascular death or hospitalization for HF during follow-up. The study showed that cardiovascular death or hospitalization related to HF occurred in 475 patients (31.0%) in the ferric carboxymaltose arm and 494 patients (32.2%) in the placebo group (hazard ratio, 0.93; 96% CI, 0.81 to 1.06) during follow-up.
Another secondary outcome was change in 6-minute walk distance from baseline to 12 months, which was 5±71 m in the ferric carboxymaltose group and 4±72 m in the placebo group. Both arms experienced similar rates of serious adverse events during the treatment period (27.0% in the ferric carboxymaltose group and 26.2% in placebo).
Iron deficiency is common among patients with HF, but those with this deficiency are considered to have worse outcomes than those without iron deficiency. Altough oral iron therapy was not found to be effective for exercise capacity among patients with HF, ejection fraction, or iron deficiency, other trials show that “intravenous ferric carboxymaltose treatment improved the quality of life and functional capacity in [these] patients.”
The HEART-FID trial included a total of 3065 ambulatory patients with similar baseline characteristics: HF, a left ventricular ejection fraction of 40% or less, and iron deficiency. Patients were split into 2 arms, with 1532 patients receiving intravenous ferric carboxymaltose and 1533 patients receiving placebo, and both arms also received standard therapy for HF.
Limitations included missing data related to the walking distance at follow up. Investigators also did not account for the effects of ferric carboxymaltose on patients who were taking other medications, such as sodium-glucose cotransporter 2 inhibitors. Finally, the study took place during the COVID-19 pandemic, which may have influenced the results, according to the authors.
Mentz RJ, Garg J, Rockhold FW, et al. Ferric Carboxymaltose in Heart Failure with Iron Deficiency. N Engl J Med. 2023.DOI: 10.1056/NEJMoa2304968