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Treatment of heart failure in adults with thalassemia major: response in patients randomised to deferoxamine with or without deferiprone

John B Porter112*, John Wood2, Nancy Olivieri3, Elliott P Vichinsky4, Ali Taher5, Ellis Neufeld6, Patricia Giardina7, Alexis Thompson8, Blaine Moore9, Patricia Evans1, Hae-Young Kim10, Eric A Macklin11 and Felicia Trachtenberg10

Author Affiliations

1 University College London, London, UK

2 Children’s Hospital of Los Angeles, Los Angeles, USA

3 Toronto General Hospital, University Health Network, Toronto, ON, Canada

4 Children’s Hospital & Research Center Oakland, Oakland, CA, USA

5 American University of Beirut, Beirut, Lebanon

6 Children’s Hospital, Boston, MA, USA

7 Weill Medical College of Cornell University, New York, NY, USA

8 Children’s Memorial Hospital, Chicago, IL, USA

9 National Heart, Lung and Blood Institute (NHLBI), Bethesda, MD, USA

10 New England Research Institutes, Watertown, MA, USA

11 Massachusetts General Hospital, Boston, MA, USA

12 Department of Haematology, University College London, UCL Cancer Institute, Paul O’Gorman Building, 72 Huntley Street, London WC1E 6BT, UK

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Journal of Cardiovascular Magnetic Resonance 2013, 15:38  doi:10.1186/1532-429X-15-38

Published: 20 May 2013

Abstract

Background

Established heart failure in thalassaemia major has a poor prognosis and optimal management remains unclear.

Methods

A 1 year prospective study comparing deferoxamine (DFO) monotherapy or when combined with deferiprone (DFP) for patients with left ventricular ejection fraction (LVEF) <56% was conducted by the Thalassemia Clinical Research Network (TCRN). All patients received DFO at 50–60 mg/kg 12–24 hr/day sc or iv 7 times weekly, combined with either DFP 75 at mg/kg/day (combination arm) or placebo (DFO monotherapy arm). The primary endpoint was the change in LVEF by CMR.

Results

Improvement in LVEF was significant in both study arms at 6 and 12 months (p = 0.04), normalizing ventricular function in 9/16 evaluable patients. With combination therapy, the LVEF increased from 49.9% to 55.2% (+5.3% p = 0.04; n = 10) at 6 months and to 58.3% at 12 months (+8.4% p = 0.04; n = 7). With DFO monotherapy, the LVEF increased from 52.8% to 55.7% (+2.9% p = 0.04; n = 6) at 6 months and to 56.9% at 12 months (+4.1% p = 0.04; n = 4). The LVEF trend did not reach statistical difference between study arms (p = 0.89). In 2 patients on DFO monotherapy during the study and in 1 patient on combined therapy during follow up, heart failure deteriorated fatally. The study was originally powered for 86 participants to determine a 5% difference in LVEF improvement between treatments. The study was prematurely terminated due to slow recruitment and with the achieved sample size of 20 patients there was 80% power to detect an 8.6% difference in EF, which was not demonstrated. Myocardial T2* improved in both arms (combination +1.9 ± 1.6 ms p = 0.04; and DFO monotherapy +1.9 ± 1.4 ms p = 0.04), but with no significant difference between treatments (p = 0.65). Liver iron (p = 0.03) and ferritin (p < 0.001) both decreased significantly in only the combination group.

Conclusions

Both treatments significantly improved LVEF and myocardial T2*. Although this is the largest and only randomized study in patients with LV decompensation, further prospective evaluation is needed to identify optimal chelation management in these high-risk patients.

Keywords:
Thalassemia; Heart failure; Deferoxamine; Deferiprone; Combination