Comparative effects of deferiprone and deferoxamine on survival and cardiac disease in patients with thalassaemia major: a retrospective analysis

Authors
Antonio Piga, Carmen Gaglioti, Eugenia Fogliacco, Fernando Tricta

Journal
Journal of Hematology, Haematologica, Volume 88, No. 5, pp 489-496, May 2003.

Background
The leading cause of death for thalassaemia patients with iron overload is iron-induced cardiac disease. Despite chelation therapy with deferoxamine, 71% of thalassaemia patients die as a result of cardiac problems (Borgna – Pignatti, 2001). Deferiprone is a small, orally active, lipophilic bidentate molecule that theoretically gives it the potential to be more effective than deferoxamine in removing intracellular iron from certain tissues. Link et al. reported that deferiprone, at clinically relevant concentrations, was more effective than deferoxamine at removing iron from iron-loaded neonatal rat myocytes (Link, 2001). These data are consistent with reports of lower incidence of iron-induced cardiac complications during deferiprone treatment. 

Methods

• Retrospective analysis on survival and occurrence of cardiac disease in all patients with thalassaemia treated for at least 4 years with either deferoxamine or deferiprone at a single center between January 31, 1995 and March 29, 2001.
• Inclusion criteria included: (1) Patients aged ³ 5 years at the start of the review period, (2) diagnosis of thalassaemia major confirmed by DNA analysis, (3) transfusion dependency.
• Deferiprone (Ferriprox® ®, Apotex Inc.) was prescribed at the dose of 25 – 100 mg/kg/day, divided in 3 doses.
• Deferoxamine (Desferal ®, Novartis Inc.) was prescribed at the dose of 20 – 50 mg/kg/day as an 8 – 12 hour subcutaneous infusion, 4 – 7 days a week.
• A single cardiologist, blinded to the therapy the patients were receiving, experienced in haemoglobinopathies, performed the cardiac assessments. The standard assessment included a physical examination, ECG, echocardiogram, and cardiac status according to the New York Heart Association (NYHA) (Dolgin, M 1994). The first assessment was considered the baseline.

Results – Fewer patients in the deferiprone group had a worsening of cardiac disease.

Seven out of 54 patients in the deferiprone group and 12 out of 75 patients in the deferoxamine group had abnormal cardiac function at the first cardiac assessment. None of the 7 patients in the deferiprone group had a worsening of cardiac disease, and 4 of the 12 (33%) deferoxamine-treated patients experienced a worsening of their cardiac disease. There was an improvement of cardiac disease in 3 of the 7 (43%) patients in the deferiprone-treated group and in 3 of the 12 (25%) patients in the deferoxamine-treated group.

Results – Fewer patients in the deferiprone-treated group developed newly diagnosed cardiac disease. 

Newly diagnosed cardiac disease occurred in 2 of the 47 (4%) deferiprone-treated patients, and in 13 of the 63 (21%) deferoxamine-treated patients who were free of cardiac disease at their first cardiac assessment. 

Results – Kaplan Meier analysis of cardiac disease-free survival was significantly more favorable in the deferiprone group (p = 0.003).

Conclusion
This retrospective study suggests that deferiprone may have a cardioprotective effect. Future prospective studies need to be conducted to compare the incidence of cardiac disease in deferiprone and deferoxamine-treated patients.

• If you would like to read the entire Piga study (external site), click here.

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