What studies examined iron deficiency in congestive heart failure (CHF)?

From the Guidelines

Intravenous iron therapy, specifically ferric carboxymaltose, is the most effective treatment for iron deficiency in congestive heart failure (CHF) patients, as it improves symptoms, functional capacity, and quality of life, and reduces hospitalization risk, as demonstrated by the FAIR-HF and CONFIRM-HF trials 1. The FAIR-HF trial, published in 2016, showed that intravenous ferric carboxymaltose improved self-reported patient global assessment, quality of life, and NYHA class in iron-deficient CHF patients, both with and without anemia 1. The CONFIRM-HF study, also published in 2016, demonstrated that intravenous ferric carboxymaltose improved exercise capacity and reduced the risk of hospitalization in CHF patients with iron deficiency over a 52-week period 1. More recently, the AFFIRM-AHF trial, published in 2022, showed that intravenous ferric carboxymaltose reduced heart failure hospitalizations after an acute heart failure episode in patients with reduced ejection fraction 1. Key points to consider when treating iron deficiency in CHF patients include:

• Iron deficiency is common in CHF patients and can lead to anemia and/or skeletal muscle dysfunction without anemia 1
• Intravenous iron therapy has been shown to improve functional capacity, HF symptoms, and health-related quality of life, and may reduce the risk of HF-related hospitalizations 1
• The 2016 ESC HF guidelines recommend evaluating iron status as part of the initial work-up of all newly diagnosed HF patients and checking iron status among patients with existing CHF independently of Hb level or when symptoms persist despite receiving optimal background HF medications 1
• The use of ferric carboxymaltose has not been studied in children, and therefore is not recommended in children under 14 years 1

From the FDA Drug Label

Trial 3: FER-CARS-05 (CONFIRM-HF) was a randomized, double-blind, placebo-controlled, study in patients with iron deficiency and chronic heart failure with left ventricular ejection fraction of < 45% and New York Heart Association (NYHA) class II/III to determine whether intravenous Injectafer improves exercise capacity measured as change from baseline to 24 weeks in 6-minute walk distance (6MWD). The safety of Injectafer was evaluated in adult patients with iron deficiency and heart failure in randomized controlled trials FAIR-HF (NCT00520780), CONFIRM-HF (NCT01453608) and AFFIRM-AHF (NCT02937454) in which 1,016 patients received Injectafer versus 857 received placebo.

The studies that examined iron deficiency in congestive heart failure (CHF) are:

• CONFIRM-HF (NCT01453608): a randomized, double-blind, placebo-controlled study that evaluated the efficacy and safety of intravenous ferric carboxymaltose in patients with iron deficiency and chronic heart failure.
• FAIR-HF (NCT00520780): a randomized controlled trial that evaluated the safety of ferric carboxymaltose in adult patients with iron deficiency and heart failure.
• AFFIRM-AHF (NCT02937454): a randomized controlled trial that evaluated the safety of ferric carboxymaltose in adult patients with iron deficiency and heart failure. These studies are referenced in 2 and 2.

From the Research

Studies Examining Iron Deficiency in Congestive Heart Failure (CHF)

• The study published in the Journal of cardiovascular pharmacology and therapeutics 3 investigated the use of IV sodium ferric gluconate complex in patients hospitalized due to acute decompensated heart failure and iron deficiency, finding that patients treated with IV iron had comparable ADHF readmission rates to those who did not receive iron supplementation.
• A retrospective analysis published in Annals of hematology 4 found that correction of iron deficiency in hospitalized heart failure patients did not improve patient outcomes, with no significant reduction in readmissions for HF or mortality between those who received IVFe and those who did not.
• The AFFIRM-AHF trial, published in Lancet (London, England) 5, evaluated the effect of ferric carboxymaltose on outcomes in patients who were stabilized after an episode of acute heart failure, finding that treatment with ferric carboxymaltose reduced the risk of heart failure hospitalizations with no apparent effect on the risk of cardiovascular death.
• A review published in Frontiers in cardiovascular medicine 6 discussed iron deficiency as a new target for patients with heart failure, highlighting the importance of iron replacement therapy in improving symptoms, quality of life, and functional capacity in patients with stable, symptomatic, iron-deficient HF.
• An audit published in Cureus 7 found that iron deficiency remains under-recognized and undertreated in clinical practice among heart failure patients, with only 74% of patients having their iron status checked and 65% of iron-deficient patients receiving iron replacement therapy.