Short- and long-term efficacy of oral stabilized bivalent liposomal iron versus intravenous ferric carboxymaltose in chronic heart failure patients: is there a difference?

Background Iron deficiency (ID) is a frequent comorbidity in chronic heart failure (CHF), affecting up to 50% of patients and strongly associated with increased mortality, worse symptoms, and impaired quality of life. In these patiens, chronic inflammation induces hepcidin overexpression, which inhibits intestinal iron absorption and traps iron in macrophages, leading to functional ID. Intravenous (IV) ferric carboxymaltose (FCM) is currently the standard therapy for rapid iron repletion, although concerns remain regarding long-term sustainability and potential oxidative stress. Stabilized bivalent liposomal iron is an oral formulation designed to bypass hepcidin-mediated blockade via alternative absorption mechanisms such as endocytosis and phagocytosis. This study compared the short- and long-term efficacy of oral liposomal iron versus IV FCM in CHF patients. Methods 61 CHF patients with confirmed ID were enrolled and randomized into two groups. 31 patients received oral stabilized bivalent liposomal iron (30 mg twice daily for one month, then once daily for two months), while 30 patients received IV FCM (one infusion at baseline and one after three months). Serum iron, hemoglobin, transferrin saturation (TSAT), ferritin, and C-reactive protein (CRP) were assessed at baseline, 48 hours, three months, and six months. Results The two treatments showed markedly different kinetic profiles. IV FCM induced a rapid and pronounced increase in ferritin and TSAT, accompanied by a significant rise in CRP at 48 hours, suggesting an acute inflammatory or oxidative response. At three and six months, serum iron and TSAT values largely returned to baseline, indicating rapid utilization or clearance of the IV iron load. Conversely, the oral liposomal iron group demonstrated a gradual and significant increase in serum iron, hemoglobin, and TSAT at three months, with stable ferritin levels. At six months, these patients maintained significantly higher hemoglobin, serum iron, and TSAT compared with baseline, indicating a more durable effect. Conclusions The different long-term outcomes reflect distinct pathophysiological mechanisms. IV iron represents an immediate exogenous load that, while effective for rapid correction, may induce transient oxidative stress and is susceptible to rapid metabolic turnover. On the other hand, the oral liposomal formulation could reduce systemic inflammation, mitigating hepcidin upregulation and restoring the physiological uptake of iron from dietary sources, which is often compromised in CHF patients. Finally, this prolonged repletion could contribute to a more stable erythropoiesis. Therefore, while IV therapy is effective for immediate intervention, oral stabilized bivalent liposomal iron demonstrates superior long-term efficacy in maintaining iron balance in CHF patients compared to IV FCM, providing a more sustainable therapeutic benefit that persists beyond the active treatment phase.