title: Effects of combined deferiprone with deferoxamine on right ventricular function in thalassaemia major.
abstract: BACKGROUND
  Combination therapy with deferoxamine and oral deferiprone is superior to deferoxamine alone in removing cardiac iron and improving left ventricular ejection fraction (LVEF). The right ventricle (RV) is also affected by the toxic effects of iron and may cause additional cardiovascular perturbation. We assessed the effects of combination therapy on the RV in thalassaemia major (TM) using cardiovascular magnetic resonance (CMR).
  
  
  METHODS
  We retrieved imaging data from 2 treatment trials and re-analyzed the data for the RV responses: Trial 1 was a randomized controlled trial (RCT) of 65 TM patients with mild-moderate cardiac siderosis receiving combination therapy or deferoxamine with placebo; Trial 2 was an open label longitudinal trial assessing combination therapy in 15 TM patients with severe iron loading.
  
  
  RESULTS
  In the RCT, combination therapy with deferoxamine and deferiprone was superior to deferoxamine alone for improving RVEF (3.6 vs 0.7%, p = 0.02). The increase in RVEF was greater with lower baseline T2* 8-12 ms (4.7 vs 0.5%, p = 0.01) than with T2* 12-20 ms (2.2 vs 0.8%, p = 0.47). In patients with severe cardiac siderosis, substantial improvement in RVEF was seen with open-label combination therapy (10.5% ± 5.6%, p < 0.01).
  
  
  CONCLUSIONS
  In the RCT of mild to moderate cardiac iron loading, combination treatment improved RV function significantly more than deferoxamine alone. Combination treatment also improved RV function in severe cardiac siderosis. Therefore adding deferiprone to deferoxamine has beneficial effects on both RV and LV function in TM patients with cardiac siderosis.
authors.affiliation: Royal Brompton & Harefield NHS Foundation Trust, London, UK.
authors.forename: Francisco
authors.initials: F
authors.lastname: Alpendurada
authors.forename: Gill C
authors.initials: GC
authors.lastname: Smith
authors.forename: John-Paul
authors.initials: JP
authors.lastname: Carpenter
authors.forename: Sunil V
authors.initials: SV
authors.lastname: Nair
authors.forename: Mark A
authors.initials: MA
authors.lastname: Tanner
authors.forename: Winston
authors.initials: W
authors.lastname: Banya
authors.forename: Carlo
authors.initials: C
authors.lastname: Dessi
authors.forename: Renzo
authors.initials: R
authors.lastname: Galanello
authors.forename: John Malcolm
authors.initials: JM
authors.lastname: Walker
authors.forename: Dudley J
authors.initials: DJ
authors.lastname: Pennell
mesh_terms: D000328:Adult; D000704:Analysis of Variance; D016009:Chi-Square Distribution; D000077543:Deferiprone; D003676:Deferoxamine / Q000627:therapeutic use*; D004359:Drug Therapy, Combination; D015150:Echocardiography, Doppler; D005260:Female; D006486:Hemosiderosis / Q000175:diagnosis / Q000188:drug therapy* / Q000209:etiology / Q000503:physiopathology; D006801:Humans; D007502:Iron Chelating Agents / Q000627:therapeutic use*; D008279:Magnetic Resonance Imaging; D008297:Male; D011728:Pyridones / Q000627:therapeutic use*; D016032:Randomized Controlled Trials as Topic; D020127:Recovery of Function; D012189:Retrospective Studies; D012720:Severity of Illness Index; D017262:Siderophores / Q000627:therapeutic use*; D013318:Stroke Volume / Q000187:drug effects; D013812:Therapeutics; D013997:Time Factors; D018497:Ventricular Dysfunction, Right / Q000175:diagnosis / Q000188:drug therapy* / Q000209:etiology / Q000503:physiopathology; D016278:Ventricular Function, Right / Q000187:drug effects*; D017086:beta-Thalassemia / Q000150:complications / Q000175:diagnosis / Q000188:drug therapy* / Q000503:physiopathology
chemical_list: D007502:Iron Chelating Agents; D011728:Pyridones; D017262:Siderophores; D000077543:Deferiprone; D003676:Deferoxamine