The HEART-FID trial, as published in the New England Journal of Medicine in 2023, was a randomized, double-blind, placebo-controlled study designed to determine the efficacy and safety of intravenous ferric carboxymaltose (FCM) in treating patients with heart failure with reduced ejection fraction (HFrEF) and iron deficiency.
The trial included 3,065 patients who were at least 18 years old with HFrEF (left ventricular ejection fraction (LVEF) ≤40%), hemoglobin levels within a specified range, iron deficiency, and either hospitalization for heart failure within the past 12 months or elevated B-type natriuretic peptide (BNP) levels. Participants were randomized to receive either intravenous ferric carboxymaltose (n=1532) or a placebo (n=1533).
The primary outcomes measured were death by month 12 and hospitalizations for heart failure. Secondary outcomes included the mean change from baseline to 6 months in the 6-minute walk distance. Results showed a death rate of 8.6% in the FCM group compared to 10.3% in the placebo group. Hospitalizations for heart failure were 13.3% for the FCM group versus 14.8% for the placebo group. There was also an improvement in the 6-minute walk distance with a mean change of 8 meters in the FCM group compared to 4 meters in the placebo group.
However, the p-value for the primary outcome was 0.019, which was above the threshold for significance set at <0.01. The overall win ratio was 1.10 (95% CI, 0.99 to 1.23), indicating no apparent difference between ferric carboxymaltose and placebo with respect to the hierarchical composite of death, hospitalizations for heart failure, or the 6-minute walk distance.
The conclusion of the HEART-FID trial was that among ambulatory patients with heart failure with a reduced ejection fraction and iron deficiency, treatment with ferric carboxymaltose did not show a significant difference compared to placebo in terms of mortality, hospitalization for heart failure, or improvement in functional capacity as measured by the 6-minute walk distance.
The findings of the HEART-FID trial contribute important information regarding the treatment of heart failure patients with iron deficiency, suggesting that while intravenous FCM may have some benefits, it does not lead to a significant difference in the primary composite outcomes within the trial’s parameters. This has implications for clinical practice, as it calls for a careful consideration of the benefits and limitations of iron supplementation in the management of patients with HFrEF.