Systematic review and meta‐analysis of intravenous iron‐carbohydrate complexes in HFrEF patients with iron deficiency

Abstract

Iron deficiency (ID) is a common co‐morbidity in patients with heart failure (HF). The present meta‐analysis evaluates the effect of intravenous (IV) iron‐carbohydrate complex supplementation in patients with HF with reduced ejection fraction (HFrEF) and ID/iron deficiency anaemia (IDA). Randomized controlled trials (RCTs) comparing IV iron‐carbohydrate complexes with placebo/standard of care in patients with HFrEF with ID/IDA were identified using Embase (from 1957) and PubMed (from 1989) databases through 25 May 2021. Twelve RCTs including 2381 patients were included in this analysis. The majority (90.8%) of patients receiving IV iron‐carbohydrate therapy were administered ferric carboxymaltose (FCM); 7.5% received iron sucrose and 1.6% received iron isomaltoside. IV iron‐carbohydrate therapy significantly reduced hospitalization for worsening HF [0.53 (0.42–0.65); P < 0.0001] and first hospitalization for worsening HF or death [0.75 (0.59–0.95); P = 0.016], but did not significantly impact all‐cause mortality, compared with control. IV iron‐carbohydrate therapy significantly improved functional and exercise capacity compared with the control. There was no significant difference in outcome between IV iron‐carbohydrate formulations when similar endpoints were measured. No significant difference in adverse events (AE) was observed between the treatment groups. IV iron‐carbohydrate therapy resulted in improvements in a range of clinical outcomes and increased functional and exercise capacity, whereas AEs were not significantly different between IV iron‐carbohydrate and placebo/standard of care arms. These findings align with the European Society of Cardiology's 2021 HF guidelines, which recommend the consideration of FCM in symptomatic patients with a left ventricular ejection fraction < 45% and ID.

Effect of intravenous iron replacement on recurrent heart failure hospitalizations and cardiovascular mortality in patients with heart failure and iron deficiency: A Bayesian meta‐analysis

“…Furthermore, approximately 50% of HF patients are iron-deficient and thus eligible for therapy; widespread adoption of IV iron supplementation could therefore reduce the burden of HF hospitalizations on a population level. Two recent -to some degree preliminary -meta-analyses have confirmed this, 30,31 and that IV iron is also an attractive treatment option in other cardiovascular disease contexts. 20 Two large-scale trials, FAIR-HF2 (NCT03036462) and HEART-FID (NCT03037931) are ongoing to study the effect of IV iron over a 1-year follow-up and will provide further evidence in the area.…”

A year in heart failure: updates of clinical and preclinical findings

“…Indeed, a meta‐analysis has recently shown that IV iron‐carbohydrate therapy significantly reduces hospitalization for worsening HF [hazard ration with 95% confidence intervals 0.53 (0.42–0.65); P < 0.0001] and first hospitalization for worsening HF or death [0.75 (0.59–0.95); P = 0.016], but it did not significantly impact all‐cause mortality. No significant differences in adverse events were observed between the treatment groups 50 . A retrospective database analysis has shown that IV iron administration appears to improve ejection fraction and cardiac functional status in outpatients with iron deficiency, HFpEF, and HFrEF 52 …”

“…In clinical practice, however, iron deficiency remains underdiagnosed and undertreated 49 . Several intravenous (IV) iron products have been used in HF trials; however, the ESC guidelines currently only recommend ferric carboxymaltose 50 . This recommendation may change after the IRONMAN trial has been published recently that demonstrated beneficial effects of the use of ferric derisomaltose in patients with HFrEF 51 .…”

“…49 Several intravenous (IV) iron products have been used in HF trials; however, the ESC guidelines currently only recommend ferric carboxymaltose. 50 This recommendation may change after the IRONMAN trial has been published recently that demonstrated beneficial effects of the use of ferric derisomaltose in patients with HFrEF. 51 Indeed, a meta-analysis has recently shown that IV iron-carbohydrate therapy significantly reduces hospitalization for worsening HF [hazard ration with 95% confidence intervals 0.53 (0.42-0.65); P < 0.0001] and first hospitalization for worsening HF or death [0.75 (0.59-0.95); P = 0.016], but it did not significantly impact all-cause mortality.…”

“…No significant differences in adverse events were observed between the treatment groups. 50 A retrospective database analysis has shown that IV iron administration appears to improve ejection fraction and cardiac functional status in outpatients with iron deficiency, HFpEF, and HFrEF. 52 Another important aspect in the individualization of HF therapy is the use of vericiguat in patients with a recent episode of worsening HF requiring IV diuretic treatment.…”