title: Treatment of heart failure in adults with thalassemia major: response in patients randomised to deferoxamine with or without deferiprone.
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.
authors.forename: John B
authors.initials: JB
authors.lastname: Porter
authors.forename: John
authors.initials: J
authors.lastname: Wood
authors.forename: Nancy
authors.initials: N
authors.lastname: Olivieri
authors.forename: Elliott P
authors.initials: EP
authors.lastname: Vichinsky
authors.forename: Ali
authors.initials: A
authors.lastname: Taher
authors.forename: Ellis
authors.initials: E
authors.lastname: Neufeld
authors.forename: Patricia
authors.initials: P
authors.lastname: Giardina
authors.forename: Alexis
authors.initials: A
authors.lastname: Thompson
authors.forename: Blaine
authors.initials: B
authors.lastname: Moore
authors.forename: Patricia
authors.initials: P
authors.lastname: Evans
authors.forename: Hae-Young
authors.initials: HY
authors.lastname: Kim
authors.forename: Eric A
authors.initials: EA
authors.lastname: Macklin
authors.forename: Felicia
authors.initials: F
authors.lastname: Trachtenberg
mesh_terms: D000328:Adult; D000077543:Deferiprone; D003676:Deferoxamine / Q000627:therapeutic use*; D004359:Drug Therapy, Combination; D005260:Female; D006333:Heart Failure / Q000175:diagnosis / Q000188:drug therapy* / Q000209:etiology / Q000503:physiopathology; D006801:Humans; D007502:Iron Chelating Agents / Q000627:therapeutic use*; D007861:Lebanon; D008297:Male; D009864:Ontario; D011446:Prospective Studies; D011728:Pyridones / Q000627:therapeutic use*; D020127:Recovery of Function; D017262:Siderophores / Q000627:therapeutic use*; D013318:Stroke Volume / Q000187:drug effects; D013997:Time Factors; D016896:Treatment Outcome; D014481:United States; D016277:Ventricular Function, Left / Q000187:drug effects; D055815:Young Adult; D017086:beta-Thalassemia / Q000150:complications / Q000175:diagnosis / Q000188:drug therapy*
chemical_list: D007502:Iron Chelating Agents; D011728:Pyridones; D017262:Siderophores; D000077543:Deferiprone; D003676:Deferoxamine