A randomized, controlled study evaluating effects of amlodipine addition to chelators to reduce iron loading in patients with thalassemia major

Kazemi, Hamideh; Taherahmadi, Hassan; Ghandi, Yazdan; Rafiei, Mohammad; Bagheri, Bahador

doi:10.1111/ejh.12977

Cited by 23 publications

(34 citation statements)

References 15 publications

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“…A limited number of human studies have shown a significant reduction in MIC after using amlodipine 26–28. Hence, we conducted a randomized, controlled-placebo study to demonstrate the efficacy of amlodipine, in addition to chelation therapy, in reducing myocardial iron concentration.…”

Section: Introductionmentioning

confidence: 99%

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

Khaled¹,

Salem²,

Ezzat³

et al. 2019

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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.

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Section: Introductionmentioning

confidence: 99%

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

Khaled¹,

Salem²,

Ezzat³

et al. 2019

DDDT

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“…Despite incomplete characterization of iron-induced K + current alterations, amiodarone has been used to treat supraventricular arrhythmias commonly found in iron-overload patients ( Pennell et al, 2013 ). Potential role of LTCC blockers as an inhibitor of cardiac iron uptake is also being evaluated in clinical trials ( Fernandes et al, 2013 , 2016 ; Shakoor et al, 2014 ; Eghbali et al, 2017 ; Sadaf et al, 2018 ). It is still unknown whether the use of LTCC blockers will exert any significant electrophysiological effects.…”

Section: Forging the Field: Additional Issues To Be Explored In Iron-mentioning

confidence: 99%

Cellular Electrophysiology of Iron-Overloaded Cardiomyocytes

2018

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Iron, the most abundant transition metal element in the human body, plays an essential role in many physiological processes. However, without a physiologically active excretory pathway, iron is subject to strict homeostatic processes acting upon its absorption, storage, mobilization, and utilization. These intricate controls are perturbed in primary and secondary hemochromatoses, leading to a deposition of excess iron in multiple vital organs including the heart. Iron overload cardiomyopathy is the leading cause of mortality in patients with iron overload conditions. Apart from mechanical deterioration of the siderotic myocardium, arrhythmias reportedly contribute to a substantial portion of cardiac death associated with iron overload. Despite this significant impact, the cellular mechanisms of electrical disturbances in an iron-overloaded heart are still incompletely characterized. This review article focuses on cellular electrophysiological studies that directly investigate the effects of iron overload on the function of cardiac ion channels, including trans-sarcolemmal and sarcoplasmic reticulum Ca2+ fluxes, as well as cardiac action potential morphology. Our ultimate aim is to provide a comprehensive summary of the currently available information that will encourage and facilitate further mechanistic elucidation of iron-induced pathoelectrophysiological changes in the heart.

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“…Iron overload is an important cause of mortality and morbidity in chronic transfusion-dependent states commonly exemplified by transfusion-dependent beta-thalassaemia syndromes [including non-transfusion-dependent (NTD) thalassaemia intermedia] as well as transfusion-dependent myelodysplastic syndromes (MDS). Hence, therapeutic iron chelation is indicated in these conditions12345. There seems to be an increasing interest for different iron chelators and labile iron pool for patients with thalassaemia syndromes (thalassaemia major and thalassaemia intermedia) and transfusion-dependent MDS with respect to their efficacy, tolerability, safety, cost and long-term side effects.…”

mentioning

confidence: 99%

“…There seems to be an increasing interest for different iron chelators and labile iron pool for patients with thalassaemia syndromes (thalassaemia major and thalassaemia intermedia) and transfusion-dependent MDS with respect to their efficacy, tolerability, safety, cost and long-term side effects. Several studies have been published recently on this topic123456789. Di Maggio and Maggio4 evaluated 10 trials on various iron chelators singly or in combination for iron overloaded transfusion-dependent beta-thalassaemia major.…”

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confidence: 99%

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Iron chelators or therapeutic modulators of iron overload: Are we anywhere near ideal one?

Ghosh¹,

Ghosh²

2018

Indian J Med Res

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A randomized, controlled study evaluating effects of amlodipine addition to chelators to reduce iron loading in patients with thalassemia major

Abstract: Addition of amlodipine to iron chelators has beneficial effects for reduction of iron loading in patients with thalassemia major. This combination therapy seems safe.

Cited by 23 publications

References 15 publications

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

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

Cellular Electrophysiology of Iron-Overloaded Cardiomyocytes

Iron chelators or therapeutic modulators of iron overload: Are we anywhere near ideal one?

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