Long-acting efficacy of oral stabilized bivalent liposomal iron therapy on iron balance and quality of life in chronic heart failure: more than iron supplementation

Background Iron deficiency (ID) affects up to 50% of patients with chronic heart failure (CHF) and is associated with higher mortality, worse symptoms, and reduced quality of life. In these patients, chronic inflammation promotes functional iron deficiency through a hepcidin-mediated blockade of gastrointestinal absorption, reducing iron availability and worsening anemia. The stabilized bivalent liposomal iron formulation bypasses the hepcidin-blocked absorption pathway and has already shown, in a previous trial, its efficacy in improving iron bioavailability and quality of life in CHF. The aim of our study was to assess the long-term effects of stabilized bivalent liposomal iron therapy on iron balance and quality of life in CHF patients after treatment discontinuation. Methods Forty-two patients with CHF and confirmed ID were enrolled. ID was defined as ferritin <100 μg/L or ferritin 100–299 μg/L with transferrin saturation (TSAT) <20%. Patients received oral stabilized bivalent liposomal iron sulfate at 30 mg twice daily for one month, then once daily for two additional months. Blood parameters, including serum iron, ferritin, TSAT and hemoglobin, along with Kansas City Cardiomyopathy Questionnaire (KCCQ) scores were meticulously assessed at baseline, immediately after the three-month treatment period, and again at a six-month follow-up after treatment discontinuation. Results Data are reported in Table 1. After three months of therapy, serum iron, ferritin, TSAT and hemoglobin significantly improved, compared with baseline. Six months after the end of therapy, the parameters showed a slight decrease but remained significantly higher than baseline. KCCQ Overall Summary Score significantly improved after three months of therapy, and after six months from discontinuation of the therapy it was still significantly higher than baseline. Conclusions The sustained efficacy of stabilized bivalent liposomal iron therapy on iron balance and quality of life suggests a therapeutic effect that extends beyond conventional iron supplementation. This benefit may derive from intrinsic physiological advantages of the liposomal formulation. Mitigation of hepcidin upregulation could play a key role: by exploiting alternative absorption pathways, liposomal iron bypasses traditional enterocyte-mediated uptake, thereby limiting hepcidin induction, the master regulator that blocks iron absorption and iron release from stores. In addition, the phospholipid bilayer shields the gastrointestinal mucosa from direct iron contact, reducing oxidative stress and inflammatory signaling, which may enhance physiological absorption and increase bioavailability. Finally, prolonged repletion may support more stable erythropoiesis. Further studies should clarify the mechanisms underlying this sustained effect and assess its impact on long-term outcomes such as hospitalization and mortality in patients with CHF.