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Background and aim: This study examined whether administration of amlodipine could improve myocardial iron loading status in patients with transfusion dependent β-thalassemia (TDT), through a placebo-controlled, crossover study. Methods: Amlodipine (5 mg, daily) or placebo were prescribed to all patients (n = 19) for 6 months, and after a 2-week washout period, patients were crossed over to the other group. The efficacy of amlodipine on iron loading was assessed by measuring myocardial T2*-weighted magnetic resonance imaging (MRI T2*, millisecond [ms]) and serum ferritin (ng/mL).Results: Seventeen patients completed the study. The mean ± standard deviation[SD] of myocardial MRI T2* at baseline was 9.83 ± 2.67 ms Myocardial MRI T2* value rose to 11.44 ± 4.14 ms post amlodipine treatment in all patients. After placebo, myocardial MRI T2* value reached 10.29 ± 4.01 ms After controlling the baseline measures, Hedges's g for ferritin and myocardial MRI T2* outcomes were estimated 3.84 (95% confidence interval [CI] 2.68 to 4.97) and −1.80 (95% CI −2.58 to −0.10), respectively. Conclusion:Amlodipine might improve myocardial MRI T2* and serum ferritin level compared to placebo. However, larger clinical studies are needed to confirm the results.

Background and Aim: This study aimed to assess the antioxidant effects of amlodipine in transfusion-dependent β-thalassemia (TDT) patients.Methods: This crossover trial consisted of two sequences (AP and PA). In the AP sequence, nine cases received amlodipine 5 mg daily (phase I) and then were switched to placebo (phase II). In PA sequence, 10 patients took the placebo (phase I) and were shifted to amlodipine (phase II). The washout period was 2 weeks. The length of each phase was 6 months. Serum malondialdehyde (MDA, μmol/L), carbonyl (protein CO, μM/L), glutathione (GSH, nM/L), and total antioxidant capacity (TAC, μmol FeSO4/L) were measured in the beginning and at the end of phases I and II. The clinical significance was viewed as a minimum change difference of 5% for each outcome between amlodipine and placebo.Results: Seventeen cases completed the study. According to the baseline MDA values, the adjusted Hedges's g for MDA was −0.59, 95% confidence interval [CI] −1.26 to 0.08. After controlling the baseline protein CO values, Hedges's g computed for protein CO was −0.11, 95% CI −0.76 to 0.55. The estimated values of the adjusted Hedges's g for GSH and TAC were also 0.26, 95% CI −0.40 to 0.91, and 0.42, 95% CI −0.24 to 1.09, respectively. The change difference for MDA was 8.3% (protein CO 2.2%, GSH 3.1%, and TAC 12.9%). Conclusion: Clinically, amlodipine therapy is an efficacious adjuvant treatment with conventional iron chelators for improving the levels of MDA and TAC in patients with TDT. K E Y W O R D S amlodipine, malondialdehyde, oxidative stress, protein carbonyl, reactive oxygen species, redcell transfusion, β-thalassemia 2of10 | DARVISHI-KHEZRI et al. | INTRODUC TI ONThalassemia is well-known as the most prevailing hemoglobinopathy disorder globally. 1 Increased iron absorption and constant red-cell transfusions bring about iron overload in patients with transfusiondependent β-thalassemia (TDT). 2,3 Iron accumulation produces reactive oxygen species (ROS) through the Haber-Weiss and Fenton reactions in conjunction with the production of highly toxic hydroxyl radicals due to peroxidation. 4 ROS can damage lipids, proteins, deoxyribonucleic acid (DNA), and intracellular organelles, e.g., lysosomes and mitochondria. 5 This injury can lead to cellular dysfunction, apoptosis, and necrosis, leading to toxicity and dysfunction in the target organs. 6,7 Hydroxyl radical production and increased lipid peroxidation would be determining factors to trigger cardiac problems caused by iron surplus. [8][9][10] Various studies have shown that calcium channels are involved in iron absorption by myocardial cells. L-type calcium channel blockers (L-TCC blockers), e.g., amlodipine, are traditionally considered therapeutic options in arrhythmia and hypertension, which can inhibit calcium influx into the cell. According to studies, L-TCC blockers may reduce cellular iron uptake and oxidative stress, preventing iron damage. 11 Recent research has recommended amlodipine prescription to mitigate iron deposition into the tiss...