Ferric Derisomaltose and Risk for Recurrent Hospitalizations in HF and Iron Deficiency

Ferric derisomaltose therapy reduces risk for recurrent hospitalization and CV death in patients with heart failure and iron deficiency.

Among patients with heart failure (HF) and iron deficiency, recurrent hospitalizations for HF and cardiovascular death are numerically lower for those who received ferric derisomaltose compared with those who receive usual care. These finding were published in The Lancet.

The prospective, randomized, open-label IRONMAN (Effectiveness of Intravenous Iron Treatment versus Standard Care in Patients with Heart Failure and Iron Deficiency; ClinicalTrials.gov Identifier: NCT02642562) trial evaluated the long-term effects of repeated doses of intravenous ferric derisomaltose on hospitalization for HF and cardiovascular death in patients with HF and iron deficiency at 70 hospital sites in the UK.

Eligible participants were aged 18 years or older, with new or established symptomatic HF, evidence of iron deficiency (serum ferritin concentration <100 µg/L or transferrin saturation <20%), and a left ventricular ejection fraction of 45% or less within the preceding 24 months. Patients who received ferric derisomaltose had their estimated iron deficit determined according to hemoglobin value and body weight.

The primary endpoint was all hospital admissions for HF and cardiovascular death based on a recurrent events analysis. Secondary endpoints included hospital readmissions for HF (recurrent events), a first cardiovascular hospital admission, and cardiovascular death or hospital admission for HF (first event). Safety analyses were performed in patients assigned to ferric derisomaltose who received 1 or more infusions and in all patients who received usual care.

The consistency of the results from IRONMAN and AFFIRM-AHF suggests that there is a generic benefit accompanying intravenous iron therapy in a broad range of patients with HF with iron deficiency, which might be independent of the nature of the iron complex used.

To reduce the effect of the COVID-19 pandemic, a sensitivity analysis with all patients randomly assigned until March 31, 2020, was conducted.

A total of 1137 patients were randomly assigned in a 1:1 ratio to receive intravenous ferric derisomaltose (n=569; median age, 73.2 years; 75% men; 91% White) or usual care (n=568; median age, 73.5 years; 72% men; 92% White). The median follow-up was 2.7 years (IQR, 1.8-3.6), with a maximum of 5.4 years.

Overall, 336 primary endpoints (22.4 per 100 patient-years) occurred in participants assigned to ferric derisomaltose and 411 (27.5 per 100 patient-years) occurred in those assigned to usual care (rate ratio [RR], 0.82 [95% CI, 0.66-1.02]; P =.070).

Secondary clinical outcomes were generally favorable for patients who received ferric derisomaltose vs those assigned to usual care, although most differences were not statistically significant (hospital admissions for HF, P =.085; cardiovascular hospital admission, P =.24; cardiovascular death or hospital admission for HF, P =.081).

In the COVID-19 analysis, with censoring follow-up on September 30, 2020, the ferric derisomaltose group had 210 primary endpoints (22.3 per 100 patient-years) vs 280 (29.3 per 100 patient-years) in the usual care group (RR, 0.76 [95% CI, 0.58-1.00]; P =.047).

The ferric derisomaltose group (n=559) had 410 serious adverse events vs 435 in the usual care group (n=568; (P =.21). In addition, the ferric derisomaltose group had 200 cardiac events vs 243 in the usual care group (P =.016).

Study limitations include the predominantly White population and open-label design. Also, the event rate is lower than predicted, as fewer than expected patients admitted to the hospital were recruited, which caused the trial to be extended further into the COVID-19 pandemic. Furthermore, among the patients assigned to usual care, 95 (17%) received 1 or more nonprotocol intravenous iron infusions, which dilutes the magnitude of benefit and reduces the trial’s power.

“The consistency of the results from IRONMAN and AFFIRM-AHF suggests that there is a generic benefit accompanying intravenous iron therapy in a broad range of patients with HF with iron deficiency, which might be independent of the nature of the iron complex used,” the researchers wrote.

Disclosure: The trial was supported in part by Pharmacosmos. Some of the study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of authors’ disclosures.

References:

Kalra PR, Cleland JGF, Petrie MC, et al. 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. Published online November 5, 2022. doi: 10.1016/S0140-6736(22)02083-9