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

Journal of Cardiovascular Magnetic Resonance

Felicia Trachtenberg^1,10  Eric A Macklin⁸  Hae-Young Kim^1,10  Patricia Evans⁴  Blaine Moore⁶  Alexis Thompson^1,11  Patricia Giardina⁹  Ellis Neufeld²  Ali Taher⁷  Elliott P Vichinsky⁵  Nancy Olivieri¹  John Wood^1,12  John B Porter³ 

[1] Toronto General Hospital, University Health Network, Toronto, ON, Canada;Children’s Hospital, Boston, MA, USA;Department of Haematology, University College London, UCL Cancer Institute, Paul O’Gorman Building, 72 Huntley Street, London WC1E 6BT, UK;University College London, London, UK;Children’s Hospital & Research Center Oakland, Oakland, CA, USA;National Heart, Lung and Blood Institute (NHLBI), Bethesda, MD, USA;American University of Beirut, Beirut, Lebanon;Massachusetts General Hospital, Boston, MA, USA;Weill Medical College of Cornell University, New York, NY, USA;New England Research Institutes, Watertown, MA, USA;Children’s Memorial Hospital, Chicago, IL, USA;Children’s Hospital of Los Angeles, Los Angeles, USA

关键词: Combination;    Deferiprone;    Deferoxamine;    Heart failure;    Thalassemia;   

Others  :  829779
DOI  :  10.1186/1532-429X-15-38

 received in 2013-05-09, accepted in 2013-05-10,  发布年份 2013

【 摘 要 】

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.

【 授权许可】

   
2013 Porter et al.; licensee BioMed Central Ltd.

【 图 表 】

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