Physicians' Academy for Cardiovascular Education

Phase 3 trial with ferric carboxymaltose in HFrEF does not meet hierarchical primary endpoint

News - Aug. 26, 2023

HEART-FID: Ferric Carboxymaltose in Heart Failure with Iron Deficiency

Presented at the ESC congress 2023 by: Robert Mentz, MD - Durham, NC, USA

Introduction and methods

Iron deficiency is very common in HF, affecting ≥50% of patients. It is strongly associated with worse quality of life, less exercise capacity, more HF hospitalizations, and increased mortality. Intravenous iron therapy may improve some clinical outcomes, but more evidence is needed on its effect on hospitalization and survival.

The HEART-FID (Ferric Carboxymaltose in Heart Failure With Iron Deficiency) trial was an international, multicenter, double-blind, placebo-controlled, phase 3 RCT conducted in 3065 ambulatory patients with chronic HFrEF (LVEF ≤40%), NYHA class II–IV symptoms, and iron deficiency. Participants were randomly assigned to intravenous ferric carboxymaltose (FCM) or placebo, given every 6 months as applicable, in addition to standard HF therapy. Median follow-up duration was 1.9 years (IQR: 1.3–3.0).

The primary endpoint was a hierarchical composite outcome of all-cause mortality at 12 months, HF hospitalizations at 12 months, and change in 6-minute walk distance (6MWD) from baseline to 6 months. The top secondary endpoint was time to first HF hospitalization or CV death during follow-up. The prespecified significance level was set at 0.01.

Main results


In chronic HFrEF patients with iron deficiency, intravenous FCM treatment resulted in a modest albeit not statistically significant improvement in the hierarchical composite outcome of all-cause mortality, HF hospitalization, and change in 6MWD. Still, Dr. Mentz believes the total body of evidence supports the clinical benefits and safety of intravenous FCM in patients with HFrEF and iron deficiency.

The results of this study were simultaneously published in N Engl J Med. Watch a video by Robert Mentz

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