title: Efficacy of deferasirox in reducing and preventing cardiac iron overload in beta-thalassemia.
abstract: Cardiac iron overload causes most deaths in beta-thalassemia major. The efficacy of deferasirox in reducing or preventing cardiac iron overload was assessed in 192 patients with beta-thalassemia in a 1-year prospective, multicenter study. The cardiac iron reduction arm (n = 114) included patients with magnetic resonance myocardial T2* from 5 to 20 ms (indicating cardiac siderosis), left ventricular ejection fraction (LVEF) of 56% or more, serum ferritin more than 2500 ng/mL, liver iron concentration more than 10 mg Fe/g dry weight, and more than 50 transfused blood units. The prevention arm (n = 78) included otherwise eligible patients whose myocardial T2* was 20 ms or more. The primary end point was the change in myocardial T2* at 1 year. In the cardiac iron reduction arm, the mean deferasirox dose was 32.6 mg/kg per day. Myocardial T2* (geometric mean +/- coefficient of variation) improved from a baseline of 11.2 ms (+/- 40.5%) to 12.9 ms (+/- 49.5%) (+16%; P < .001). LVEF (mean +/- SD) was unchanged: 67.4 (+/- 5.7%) to 67.0 (+/- 6.0%) (-0.3%; P = .53). In the prevention arm, baseline myocardial T2* was unchanged from baseline of 32.0 ms (+/- 25.6%) to 32.5 ms (+/- 25.1%) (+2%; P = .57) and LVEF increased from baseline 67.7 (+/- 4.7%) to 69.6 (+/- 4.5%) (+1.8%; P < .001). This prospective study shows that deferasirox is effective in removing and preventing myocardial iron accumulation. This study is registered at http://clinicaltrials.gov as NCT00171821.
authors.affiliation: Royal Brompton Hospital, London SW3 6NP, United Kingdom. d.pennell@ic.ac.uk
authors.forename: Dudley J
authors.initials: DJ
authors.lastname: Pennell
authors.forename: John B
authors.initials: JB
authors.lastname: Porter
authors.forename: Maria Domenica
authors.initials: MD
authors.lastname: Cappellini
authors.forename: Amal
authors.initials: A
authors.lastname: El-Beshlawy
authors.forename: Lee Lee
authors.initials: LL
authors.lastname: Chan
authors.forename: Yesim
authors.initials: Y
authors.lastname: Aydinok
authors.forename: Mohsen Saleh
authors.initials: MS
authors.lastname: Elalfy
authors.forename: Pranee
authors.initials: P
authors.lastname: Sutcharitchan
authors.forename: Chi-Kong
authors.initials: CK
authors.lastname: Li
authors.forename: Hishamshah
authors.initials: H
authors.lastname: Ibrahim
authors.forename: Vip
authors.initials: V
authors.lastname: Viprakasit
authors.forename: Antonis
authors.initials: A
authors.lastname: Kattamis
authors.forename: Gillian
authors.initials: G
authors.lastname: Smith
authors.forename: Dany
authors.initials: D
authors.lastname: Habr
authors.forename: Gabor
authors.initials: G
authors.lastname: Domokos
authors.forename: Bernard
authors.initials: B
authors.lastname: Roubert
authors.forename: Ali
authors.initials: A
authors.lastname: Taher
mesh_terms: D000293:Adolescent; D000328:Adult; D001565:Benzoates / Q000008:administration & dosage* / Q000009:adverse effects; D002648:Child; D000077588:Deferasirox; D004305:Dose-Response Relationship, Drug; D005260:Female; D005293:Ferritins / Q000097:blood; D006333:Heart Failure / Q000188:drug therapy / Q000209:etiology / Q000517:prevention & control*; D006801:Humans; D007501:Iron / Q000378:metabolism; D007502:Iron Chelating Agents / Q000008:administration & dosage* / Q000009:adverse effects; D019190:Iron Overload / Q000188:drug therapy / Q000209:etiology / Q000517:prevention & control*; D008297:Male; D009206:Myocardium / Q000378:metabolism; D011446:Prospective Studies; D014230:Triazoles / Q000008:administration & dosage* / Q000009:adverse effects; D055815:Young Adult; D017086:beta-Thalassemia / Q000150:complications / Q000188:drug therapy*
chemical_list: D001565:Benzoates; D007502:Iron Chelating Agents; D014230:Triazoles; D005293:Ferritins; D007501:Iron; D000077588:Deferasirox