Published Online
on March 19, 2007

A more recent version of this article appeared on April 10, 2007

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Submitted on August 1, 2006
Accepted on January 24, 2007

A Randomized, Placebo-Controlled, Double-Blind Trial of the Effect of Combined Therapy With Deferoxamine and Deferiprone on Myocardial Iron in Thalassemia Major Using Cardiovascular Magnetic Resonance

M. A. Tanner MRCP, R. Galanello MD, C. Dessi MD, G. C. Smith MSc, M. A. Westwood MD, A. Agus MD, M. Roughton MSc, R. Assomull MRCP, S. V. Nair MRCP, J. M. Walker MD, and D. J. Pennell MD^*

From the Cardiovascular Magnetic Resonance Unit (M.A.T., G.C.S., M.A.W., R.A., D.J.P.) and Health Services Research Unit (M.R.), Royal Brompton Hospital, London, UK; Ospedale Regionale per le Microcitemie, Cagliari, Italy (R.G., C.D., A.A.); and Department of Cardiology, University College Hospital, London, UK (S.V.N., J.M.W.).

^* To whom correspondence should be addressed. E-mail: d.pennell{at}ic.ac.uk.

Background--Cardiac complications secondary to iron overload are the leading cause of death in -thalassemia major. Approximately two thirds of patients maintained on the parenteral iron chelator deferoxamine have myocardial iron loading. The oral iron chelator deferiprone has been demonstrated to remove myocardial iron, and it has been proposed that in combination with deferoxamine it may have additional effect.

Methods and Results--Myocardial iron loading was assessed with the use of myocardial T2* cardiovascular magnetic resonance in 167 patients with thalassemia major receiving standard maintenance chelation monotherapy with subcutaneous deferoxamine. Of these patients, 65 with mild to moderate myocardial iron loading (T2* 8 to 20 ms) entered the trial with continuation of subcutaneous deferoxamine and were randomized to receive additional oral placebo (deferoxamine group) or oral deferiprone 75 mg/kg per day (combined group). The primary end point was the change in myocardial T2* over 12 months. Secondary end points of endothelial function (flow-mediated dilatation of the brachial artery) and cardiac function were also measured with cardiovascular magnetic resonance. There were significant improvements in the combined treatment group compared with the deferoxamine group in myocardial T2* (ratio of change in geometric means 1.50 versus 1.24; P=0.02), absolute left ventricular ejection fraction (2.6% versus 0.6%; P=0.05), and absolute endothelial function (8.8% versus 3.3%; P=0.02). There was also a significantly greater improvement in serum ferritin in the combined group (-976 versus -233 µg/L; P<0.001).

Conclusions--In comparison to the standard chelation monotherapy of deferoxamine, combination treatment with additional deferiprone reduced myocardial iron and improved the ejection fraction and endothelial function in thalassemia major patients with mild to moderate cardiac iron loading.

Key words: deferiprone • deferoxamine • endothelium • heart failure • magnetic resonance imaging • thalassemia • trials

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