Efficacy of liposomal bivalent stabilized iron sulfate in improving iron deficiency and quality of life in patients with chronic heart failure: lower costs for better therapy?

Introduction Iron deficiency (ID), affecting up to 50% of Chronic Heart Failure (CHF) patients, is associated with higher mortality, worse symptoms, poorer quality of life and impaired exercise capacity. Chronic inflammation in CHF promotes functional ID through elevated hepcidin levels, impairing iron availability and worsening anemia. Hepcidin-induced blockade of gastrointestinal absorption can limit effectiveness of oral iron treatment. The stabilized bivalent liposomal iron bypasses the absorption channel blocked by hepcidin and is directly absorbed by enterocyte cells through endocytosis and phagocytosis, allowing immediate and high bioavailability. In previous trials, oral iron therapy has never demonstrated, unlike intravenous administration, an improvement in functional capacity and quality of life in patients with CHF. The aim of this study was to evaluate the efficacy of stabilized bivalent liposomal iron in increasing the availability of circulating iron, in patients with CHF, as well as its effects on quality of life. Methods 53 patients (29M, 24F; mean age 68±12 years) with CHF and reduced or mildly reduced ejection fraction and confirmed ID were enrolled in the study. ID was defined as ferritin levels <100 μg/L or ferritin levels of 100 to 299 μg/L along with Transferrin Saturation (TSAT)<20% Patients were randomized in a double-blind manner to receive Liposomal Bivalent Stabilized oral iron sulfate (30 mg twice daily for one month, then once daily for an additional two months) or placebo. Blood parameters (serum iron, ferritin, TSAT and hemoglobin levels) were acquired at baseline and after one month and after three months of treatment, while Kansas City Cardiomyopathy Questionnaire (KCCQ) scores were acquired at baseline and after three months of therapy. Results Baseline characteristics and blood parameters were similar in both groups and all patients were on optimal medical therapy. Blood parameters are reported in Table 1. KCCQ Overall Summary Score significantly improved, in the treatment arm, from 48.9±18.50 to 62.1±13.8 (p<0.001), while it did not significantly improve in the placebo arm (from 48.1±16.9 to 50.2±12.2, p=0.06). Conclusions The positive impact of oral stabilized bivalent liposomal iron on iron balance and quality of life underscores its potential as a therapeutic intervention for CHF patients with ID. Its ability to bypass the hepcidin-mediated absorption block allows a more effective improvement in iron balance. It increases iron bioavailability instead than quick iron storage, avoiding elevated risk of oxidative stress, direct arterial calcification and ferroptotic cell death. In addition to its efficacy, it also represents an excellent therapeutic choice in terms of cost-effectiveness. This clinical trial is the first to show that oral stabilized bivalent liposomal iron therapy improves quality of life in CHF patients as well as iron bioavailability. Future research is needed to validate these findings.