14–16 Oudit kinase assay et al16 demonstrated that treatments with L-TCC blockers such as amlodipine

and verapamil could not only lead to the inhibition of the L-TCC current in myocardial cells, but also reduced myocardial iron accumulation, decreased oxidative stress and improved survival in iron-loaded mice. Since iron overload patients can develop cardiomyopathy and heart failure,11 17 18 which serves as the major cause of death in these patients, it is important that the use of drugs such as amlodipine be studied for the prevention of myocardial iron deposition. Current clinical practice In thalassaemia major, the current practice to prevent iron overload is to start chelation therapy after the first 10–20 transfusions or when serum ferritin levels rise above 1000 µg/L. The standard recommended method of administration of chelation therapy is slow subcutaneous infusion over 8–12 h of 10% deferoxamine (desferal) solution (DFO), using an infusion pump or oral deferasirox (DFX) or oral deferiprone (DFP). The standard dose of deferoxamine is 20–40 mg/kg

for children and up to 50–60 mg/kg for adults as an 8–12 h subcutaneous infusion for a minimum of 3–5 nights a week. Patients with high degrees of iron loading or those at increased risk of cardiac complications require adjustments in chelation therapy. The dose of oral deferasirox is 20–40 mg/kg/day. Recent studies suggest a possible synergistic effect of combination therapy of DFP with DFO, especially in reducing the myocardial iron load. This has led to multiple studies aimed at assessing the effectiveness of DFO, DFP and DFX either as monotherapy or as part of combination therapy in patients with transfusion-dependent thalassaemia. The multicentre, prospective Evaluation of Patients’ Iron Chelation with Exjade (EPIC) trial has demonstrated the effectiveness of DFX as monotherapy

in reducing mild-to-moderate and severe myocardial iron load, as documented by improvements in cardiac T2* values at 12 months,19 along with persistence of these improvements from baseline even after 24 and 36 months of GSK-3 deferasirox treatment when evaluated in a substudy of these patients.20 21 Pepe et al22 demonstrated that the combined DFP+DFO regimen and DFP in monotherapy were not significantly different in removing myocardial iron and improving heart function, when followed up to 18 months. Similarly, in a meta-analysis by Maggio et al,23 myocardial iron concentration measured as T2* was found to be not statistically significantly different in the DFP+DFO versus the DFO-treated groups. This is in contrast to findings by Tanner et al,24 who have demonstrated significant improvements in the combined treatment group compared with the deferoxamine group in myocardial T2* as well as absolute LVEF. Thus, algorithms involving single or combination chelation therapies have been developed and are used in different centres.