Relation of chelation regimes to cardiac mortality and morbidity in patients with thalassaemia major: an observational study from a large Greek Unit

Abstract

Objectives: 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.

Figure 1

Comparison of annual risk of cardiac death of the years 1990–1999 compared to 2000–2008 stratified according to age.

Figure 2

Relative risk (odds ratio) of development of de novo cardiac event – DFO compared to DFP and Comb, within each stratum of haemosiderosis, as estimated by exact logistic regression analysis. Numbers on the top of each bar are the odds ratio and the respective P-value (results adjusted for sex and age).