The Impact of Ferric Derisomaltose on Cardiovascular and Noncardiovascular Events in Patients With Anemia, Iron Deficiency, and Heart Failure With Reduced Ejection Fraction

Abstract

Background: In some countries, intravenous ferric derisomaltose (FDI) is only licensed for treating iron deficiency with anemia. Accordingly, we investigated the effects of intravenous FDI in a subgroup of patients with anemia in the IRONMAN (Effectiveness of Intravenous (IV) Iron Treatment Versus Standard Care in Patients With Heart Failure and Iron Deficiency) trial.

Method and results: IRONMAN enrolled patients with heart failure, a left ventricular ejection fraction of ≤45%, and iron deficiency (ferritin <100 µg/L or transferrin saturation of <20%), 771 (68%) of whom had anemia (hemoglobin <12 g/dL for women and <13 g/dL for men). Patients were randomized, open label, to FDI (n = 397) or usual care (n = 374) and followed for a median of 2.6 years. The primary end point, recurrent hospitalization for heart failure and cardiovascular death, occurred less frequently for those assigned to FDI (rate ratio 0.78, 95% confidence interval 0.61-1.01; P = .063). First event analysis for cardiovascular death or hospitalization for heart failure, less affected by the coronavirus disease 2019 pandemic, gave similar results (hazard ratio 0.77, 95% confidence interval 0.62-0.96; P = .022). Patients randomized to FDI reported a better Minnesota Living with Heart Failure quality of life, for overall (P = .013) and physical domain (P = .00093) scores at 4 months.

Conclusions: In patients with iron deficiency anemia and heart failure with reduced left ventricular ejection fraction, intravenous FDI improves quality of life and may decrease cardiovascular events.

Graphical abstract

Fig. 1

Estimated mean frequency functions and cumulative incidence curves for key cardiovascular outcomes. (A) Cumulative events for the primary efficacy end point (cardiovascular death and hospitalizations for heart failure). Recurrent events plotted in the form of mean frequency functions. (B) Cardiovascular death or hospitalization for heart failure (first event). (C) Cardiovascular hospitalization (first event). (D) Cardiovascular death or hospitalization for stroke, myocardial infarction, or heart failure. (E) All-cause hospitalization (first event). (F) All-cause mortality or all-cause unplanned hospitalization (first event). B, C, D, E, and F show cumulative incidence functions, correcting for the competing risk of noncardiovascular death. The hazard ratios (HR) and rate ratios (RR) are with 95% confidence intervals and were adjusted for the baseline stratification variable of recruitment context (in hospital for heart failure, recent hospital admission for heart failure (within 6 months), or with elevated natriuretic peptide level.