Efficacy of deferasirox in reducing and preventing cardiac iron overload in beta-thalassemia

Blood. 2010 Mar 25;115(12):2364-71. doi: 10.1182/blood-2009-04-217455. Epub 2009 Dec 8.

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.

Publication types

  • Clinical Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Benzoates / administration & dosage*
  • Benzoates / adverse effects
  • Child
  • Deferasirox
  • Dose-Response Relationship, Drug
  • Female
  • Ferritins / blood
  • Heart Failure / drug therapy
  • Heart Failure / etiology
  • Heart Failure / prevention & control*
  • Humans
  • Iron / metabolism
  • Iron Chelating Agents / administration & dosage*
  • Iron Chelating Agents / adverse effects
  • Iron Overload / drug therapy
  • Iron Overload / etiology
  • Iron Overload / prevention & control*
  • Male
  • Myocardium / metabolism
  • Prospective Studies
  • Triazoles / administration & dosage*
  • Triazoles / adverse effects
  • Young Adult
  • beta-Thalassemia / complications
  • beta-Thalassemia / drug therapy*

Substances

  • Benzoates
  • Iron Chelating Agents
  • Triazoles
  • Ferritins
  • Iron
  • Deferasirox

Associated data

  • ClinicalTrials.gov/NCT00171821