<p>A randomized controlled trial evaluating the effects of amlodipine on myocardial iron deposition in pediatric patients with thalassemia major</p>

Abstract

Background Mortality rates increase due to iron deposition in the cardiac muscles of thalassemia major (TM) patients. Iron overload cardiomyopathy could be treated with a combination therapy of an iron chelator and an L-type calcium channel blocker. We designed a randomized controlled study to assess the potential of amlodipine, alongside chelation, in reducing myocardial iron concentration in TM patients compared with a placebo. Objectives This study aims to estimate the change in myocardial iron concentration (MIC) determined by magnetic resonance imaging after 6 months of treatment with amlodipine, as well as measuring the changes in the secondary outcomes (liver iron concentration (LIC), serum ferritin level (SF), and left ventricle ejection fraction (LVEF)) of study participants. Methods A single, randomized, placebo-controlled trial was performed in 40 β-Thalassemia major patients aged between 6 and 20 years old, who received either oral amlodipine 2.5–5 mg/day or a placebo, in addition to a Deferasirox chelation regimen in a 1:1 allocation ratio. Results After 6 months, a significant reduction was noted in the MIC of patients receiving amlodipine (n=20), compared with the patients receiving the placebo (n=20). At baseline, the mean was 0.76±0.11 mg/g dry weight, while at 6 months, the mean was 0.51±0.07 mg/g dry weight ( p <0.001). Also, there was a significant change in the myocardial T2* after 6 months; the amlodipine increased the myocardial T2* from 40.63±5.45 ms at baseline to 43.25±5.35 ms ( p <0.001). However, amlodipine did not significantly affect the secondary outcomes by the end of the study. Conclusion The addition of amlodipine to the standard chelation therapy in transfusion-dependent thalassemia major patients improves myocardial iron overload without increasing the adverse effects.

The Role of Iron in Benign and Malignant Hematopoiesis

“…VIT-2763 has been shown to ameliorate oxidative stress, improve erythropoiesis by reducing the aggregation of a chains hence mitigating iron overload in thalassemic mice (110). Iron chelators combined with amlodipine, an L-type calcium channel blocker, were also used in a recent randomized clinical trial in pediatric patients (90).…”

A double‐blind, controlled, crossover trial of amlodipine on iron overload status in transfusion dependent β‐thalassemia patients

“…9,10 Amlodipine as a calcium channel blocker (CCB) is accessible at an affordable price, oral administration, known safety profile, a long half-life (35 to 50 hours) and convenient drug. 11 The promising effect on the improvement of myocardial iron overload subsequent to amlodipine prescribed alongside standard iron chelators can propound it in the management of cardiac siderosis amongst iron overloaded thalassemia cases, without serious side effects. [11][12][13] A systematic review, comprising two randomised controlled trials (n = 74), reported that a significant boost was detectable in myocardial relaxation after amlodipine therapy in comparison to the control group.…”

“…11 The promising effect on the improvement of myocardial iron overload subsequent to amlodipine prescribed alongside standard iron chelators can propound it in the management of cardiac siderosis amongst iron overloaded thalassemia cases, without serious side effects. [11][12][13] A systematic review, comprising two randomised controlled trials (n = 74), reported that a significant boost was detectable in myocardial relaxation after amlodipine therapy in comparison to the control group. However, the results remained inconclusive due to feeble available evidence.…”

“…Several preclinical and clinical studies have published that LTCCs blocker may impede iron uptake and protect heart from iron overload 9,10 . Amlodipine as a calcium channel blocker (CCB) is accessible at an affordable price, oral administration, known safety profile, a long half‐life (35 to 50 hours) and convenient drug 11 …”

“…The authors propounded that baseline MIC can be affective on the response to amlodipine therapy. Importantly, the value of MIC at baseline would be controlled by appropriate statistical models to manage MIC measures and engender more proper effect size in coming clinical trials.In a controlled-clinical trial,11 amlodipine in addition to deferasirox chelator as a standard treatment at dose of 2.5 to 5 mg/day for 6 months in TDT patients aged 6 to 20 years old. The study results signify an improvement in MIC (Cohen's d −3.14, 95% CI −4.07 to −2.20), without increasing the adverse effects and change in left ventricular ejection fraction (LVEF).…”