Long-term treatment with deferiprone enhances left ventricular ejection function when compared to deferoxamine in...

Area of Science:

• Cardiology
• Hematology
• Pharmacology

Background:

• Thalassemia major patients face significant morbidity and mortality, primarily due to cardiac disease, despite advances in transfusion and iron chelation therapy.
• Cardiac complications remain the leading cause of death in thalassemia major, highlighting the need for effective iron chelation strategies targeting myocardial function.
• Iron-induced mitochondrial damage is a key factor in cardiac dysfunction, exacerbated by the heart's high mitochondrial content and low antioxidant capacity.

Purpose of the Study:

• To compare the long-term effects of deferiprone versus deferoxamine monotherapy on left-ventricular ejection fraction (LVEF) in patients with thalassemia major.
• To investigate the potential benefits of deferiprone in preserving or improving cardiac function in the context of chronic iron overload.

Main Methods:

• A retrospective analysis of 168 thalassemia major patients receiving continuous monotherapy with either deferoxamine (N=108) or deferiprone (N=60) for at least 5 years.
• Left-ventricular ejection fraction was assessed using echocardiography.
• Statistical analysis was performed using the generalized estimating equations model to compare LVEF between the two treatment groups.

Main Results:

• Patients treated with deferiprone demonstrated a significantly better left-ventricular ejection fraction compared to those treated with deferoxamine (coefficient 0.97; 95% CI 0.37; 1.6, p=0.002).
• The findings suggest that deferiprone may enhance myocardial cell function, potentially due to its ability to more efficiently penetrate cardiac mitochondria.
• Long-term deferiprone administration was associated with significant improvements in left-ventricular function over time relative to deferoxamine.

Conclusions:

• Long-term deferiprone monotherapy significantly improves left-ventricular function in thalassemia major patients compared to deferoxamine.
• Deferiprone's potential to mitigate iron-induced mitochondrial damage in the heart may underlie its superior cardiac benefits.
• Further confirmation through prospective, randomized clinical trials is warranted to validate these findings and establish optimal chelation strategies.