Made of Iron: A Look Into the IRONMAN Trial and Iron Deficiency in Patients With HF

Iron deficiency has been proven to be common in patients with heart failure (HF) and is an independent predictor of impaired quality of life and exercise capacity.1 Whereas earlier trials assessed iron repletion in HF for up to 1 year,2 the IRONMAN (Effectiveness of Intravenous Iron Treatment Versus Standard Care in Patients With Heart Failure and Iron Deficiency) trial was the first to assess longer-term safety and efficacy of intravenous iron in a predominately outpatient HF population.

The open-label trial in the United Kingdom randomized 1,137 patients 1:1 to either ferric derisomaltose or usual care. The dosage of iron was based on body weight and hemoglobin level. Patients were included if they had iron deficiency (transferrin saturation <20% or serum ferritin level <100 mcg/L), New York Heart Association (NYHA) class II-IV HF symptoms and left ventricular ejection fraction ≤45%. The primary outcome was cardiovascular death or HF hospitalizations.

Although the number of primary outcomes of HF hospitalizations and cardiovascular death was numerically lower in the ferric derisomaltose arm (22.4 per 100 patient-years) than in the placebo arm (27.5 per 100 patient-years), it did not reach significance (p = 0.07). In the pre-coronavirus disease 2019 (COVID-19) cohort before September 2020, the primary outcome reached significance in the experimental arm compared with the control arm (p = 0.047).

Like the AFFIRM-AHF (A Randomized, Double-Blind Placebo-Controlled Trial Comparing the Effect of Intravenous Ferric Carboxymaltose on Hospitalizations and Mortality in Iron Deficient Subjects Admitted for Acute Heart Failure), the IRONMAN trial was affected by COVID-19, especially during the lockdown period. A sensitivity analysis performed to account for COVID-19 showed that iron supplementation had a larger impact on HF hospitalization and cardiac death than did usual care, although the impact just reached statistical significance. The question then arises as to whether this is an effect of COVID-19 or to nonadherence with follow-up.

The IRONMAN trial, in contrast to the AFFIRM-AHF, assessed iron repletion in an outpatient population. Additionally, ferric derisomaltose was used rather than ferric carboxymaltose as in other major trials. Overall, the IRONMAN trial added to the growing evidence in support of checking iron studies and treating iron deficiency in patients with HF.


  1. Kalra PR, Cleland JGF, Petrie MC, et al.; IRONMAN Study Group. Intravenous ferric derisomaltose in patients with heart failure and iron deficiency in the UK (IRONMAN): an investigator-initiated, prospective, randomised, open-label, blinded-endpoint trial. Lancet 2022;400:2199-209.
  2. Ponikowski P, Kirwan BA, Anker SD, et al.; AFFIRM-AHF investigators. Ferric carboxymaltose for iron deficiency at discharge after acute heart failure: a multicentre, double-blind, randomised, controlled trial. Lancet 2020;396:1895-904.

Clinical Topics: COVID-19 Hub, Dyslipidemia, Heart Failure and Cardiomyopathies, Prevention, Lipid Metabolism, Nonstatins, Acute Heart Failure, Diet

Keywords: AHA Annual Scientific Sessions, AHA22, Stroke Volume, Ventricular Function, Left, Iron, Outpatients, Quality of Life, COVID-19, SARS-CoV-2, Heart Failure, Hospitalization, Body Weight, Dietary Supplements, Transferrins, Hemoglobins, Ferritins

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