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

Journal of Cardiovascular Magnetic Resonance

Research

Ali Taher¹  Elliott P Vichinsky²  John Wood³  Ellis Neufeld⁴  Alexis Thompson⁵  Eric A Macklin⁶  Blaine Moore⁷  Felicia Trachtenberg⁸  Hae-Young Kim⁸  Nancy Olivieri⁹  Patricia Evans^1,10  John B Porter^1,11  Patricia Giardina^1,12 

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

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

DOI  :  10.1186/1532-429X-15-38

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

来源: Springer

【 摘 要 】

BackgroundEstablished heart failure in thalassaemia major has a poor prognosis and optimal management remains unclear.MethodsA 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.ResultsImprovement 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.ConclusionsBoth 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】

CC BY   
© Porter et al.; licensee BioMed Central Ltd. 2013