Relation of chelation regimes to cardiac mortality and morbidity in patients with thalassaemia major: an observational study from a large Greek Unit.
OBJECTIVE
Cardiac complications because of transfusional iron overload are the main cause of death in thalassaemia major. New chelators and iron monitoring methods such as cardiac magnetic resonance (CMR) became available after the year 2000. We evaluated the impact of these new management options on cardiac mortality and morbidity.


METHODS
The risk of cardiac death during 1990-1999 and 2000-2008 was compared. Furthermore, after 1999, morbidity, mortality and reversal of heart failure were evaluated according to chelation regime: desferrioxamine (DFO), deferiprone (DFP) and combination therapy of DFO and DFP. We also present preliminary results for deferasirox (DFX), a new oral chelator.


RESULTS
Three hundred and fifty-four patients were included in the de novo cardiac event evaluation, while 86 were included in the improvement component. The annual risk of cardiac death in patients aged between 20-30 and 30-40 reduced from 1.52% to 0.67% and 1.87% to 0.56%, respectively, before and after the year 2000. The risk for a de novo cardiac event for DFO was 9.1 times greater than that of DFP and 23.6 than with the combination of DFP and DFO. For DFX, there was one cardiac event over 269 patient-years. The risk of cardiac death was 9.5 per 1000 patient-years for DFO, 2.5 on DFP, 1.4 on combination. In the DFX group no cardiac deaths were recorded. The odds of improvement were 8.5 times greater with DFP and 6.1 with combination therapy compared to DFO.


CONCLUSIONS
The new chelation regimes, together with CMR have contributed significantly to the reduction in cardiac morbidity and mortality in patients with thalassaemia major.
Ladis
Vassilios
V
Thalassaemia Unit, 1st Department of Paediatrics, University of Athens, Aghia Sophia Children's Hospital, Athens, Greece. thalas@paidon-agiasofia.gr
Chouliaras
Giorgos
G
Berdoukas
Vasilios
V
Moraitis
Panagiotis
P
Zannikos
Kirykos
K
Berdoussi
Eleni
E
Kattamis
Christos
C
D000293:Adolescent; D000328:Adult; D000367:Age Factors; D001565:Benzoates / Q000009:adverse effects / Q000627:therapeutic use; D002648:Child; D003643:Death; D000077588:Deferasirox; D000077543:Deferiprone; D003676:Deferoxamine / Q000009:adverse effects / Q000627:therapeutic use; D005260:Female; D006115:Greece; D006331:Heart Diseases / Q000453:epidemiology / Q000209:etiology / Q000401:mortality / Q000503:physiopathology / Q000517:prevention & control; D006801:Humans; D007501:Iron / Q000097:blood*; D007502:Iron Chelating Agents / Q000009:adverse effects / Q000627:therapeutic use; D019190:Iron Overload / Q000150:complications / Q000453:epidemiology / Q000503:physiopathology; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D011728:Pyridones / Q000009:adverse effects / Q000627:therapeutic use; D065227:Transfusion Reaction; D016896:Treatment Outcome; D014230:Triazoles / Q000009:adverse effects / Q000627:therapeutic use; D055815:Young Adult; D017086:beta-Thalassemia / Q000150:complications / Q000453:epidemiology / Q000503:physiopathology
D001565:Benzoates; D007502:Iron Chelating Agents; D011728:Pyridones; D014230:Triazoles; D000077543:Deferiprone; D007501:Iron; D003676:Deferoxamine; D000077588:Deferasirox