HEART-FID: Ferric Carboxymaltose Fails to Significantly Improve Outcomes in Patients With HFrEF, Iron Deficiency
Ferric carboxymaltose (FCM) did not improve outcomes in patients with heart failure with reduced ejection fraction (HFrEF) and iron deficiency, according to results from the HEART-FID study presented at ESC Congress 2023 and simultaneously published in New England Journal of Medicine.
Researchers enrolled 3,065 patients from 281 centers in 14 countries, all of whom had HFrEF, iron deficiency, five New York Heart Association functional class II to IV symptoms, and were on maximally tolerated background therapy for ≥2 weeks before randomization to either intravenous FCM or placebo. The average age was 69 years and 34% of participants were women.
Patients were administered doses at 0 and 7 days, and then every six months based on iron indices and hemoglobin levels. The primary endpoint was a hierarchical composite of all-cause mortality at 12 months, HF hospitalizations at 12 months, and change in 6-minute walk distance (6MWD) from baseline to six months. The secondary endpoint was a composite of time to first HF hospitalization or cardiovascular death over the duration of follow-up.
Overall results found FCM resulted in modest numerical differences compared with placebo for each of the components making up the primary endpoint. At 12 months, 131 (8.6%) and 158 (10.3%) patients died in the FCM and placebo groups, respectively, and there were 297 and 332 HF hospitalizations, respectively. The mean change in 6MWD at six months was 8±60 meters in the FCM group and 4±59 meters in the placebo group.
The main comparison result had a p-value of 0.019 which did not meet the prespecified significance level of 0.01 required for regulatory success, researchers said. Additionally, the unmatched win ratio for the overall composite, comparing FCM with placebo, was 1.10 (99% confidence interval [CI] 0.99 to 1.23; p=0.019). While this indicated 10% more "wins" with FCM, it did not meet the prespecified significance level. In terms of time to first HF hospitalization or cardiovascular death during the total duration of follow-up, there were fewer events in the FCM group than placebo (16.0 vs. 17.3 events per 100 patient-years).
"The HEART-FID trial confirmed the safety of intravenous FCM in patients with HFrEF and despite suggesting potential outcome benefits did not meet its primary efficacy endpoint," said Robert Mentz, MD, FACC, of Duke Clinical Research Institute, in Durham, NC.
In a related editorial comment, Pieter Martens, MD, PhD, and Wilfried Mullens, MD, PhD, note that "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 HF and, we hope, help clinicians determine which patients might benefit from intravenous iron supplementation."
Clinical Topics: Heart Failure and Cardiomyopathies, Acute Heart Failure
Keywords: ESC Congress, ESC23, ACC International, Heart Failure, Iron, Ferric Compounds
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