Meta-Analysis
Copyright ©The Author(s) 2025. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Cardiol. Feb 26, 2025; 17(2): 103733
Published online Feb 26, 2025. doi: 10.4330/wjc.v17.i2.103733
Combinatorial approach to treat iron overload cardiomyopathy in pediatric patients with thalassemia-major: A systematic review and meta-analysis
Moaz Safwan, Mariam Safwan Bourgleh, Aseel Alsudays, Khawaja Husnain Haider
Moaz Safwan, Mariam Safwan Bourgleh, Aseel Alsudays, Khawaja Husnain Haider, Department of Basic Sciences, Sulaiman Al Rajhi University, Al Bukairiyah 51941, Saudi Arabia
Author contributions: Haider KH designed and produced the study and its methodology; Safwan M and Bourgleh MS performed database research and the quality assessment of the included trials, screened the extracted records against eligibility criteria, and conducted the statistical analysis; Bourgleh MS, AlSudays A, and Safwan M performed the data extraction and plotting; Safwan M and AlSudays A reviewed and validated the extracted data; Safwan M and Haider KH drafted the first manuscript; and all the authors reviewed the final manuscript, read and agreed to the published version of the manuscript.
Conflict-of-interest statement: All the authors report no relevant conflicts of interest for this article.
PRISMA 2009 Checklist statement: The authors have read the PRISMA 2009 Checklist, and the manuscript was prepared and revised according to the PRISMA 2009 Checklist.
Open Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: https://creativecommons.org/Licenses/by-nc/4.0/
Corresponding author: Khawaja Husnain Haider, PhD, Professor, Department of Basic Sciences, Sulaiman Al Rajhi University, PO Box 777, Al Bukairiyah 51941, Saudi Arabia. khhaider@gmail.com
Received: November 29, 2024
Revised: January 5, 2025
Accepted: January 24, 2025
Published online: February 26, 2025
Processing time: 88 Days and 8.2 Hours
Abstract
BACKGROUND

Iron overload cardiomyopathy is a significant cause of morbidity and mortality in transfusion-dependent thalassemia patients. Standard iron chelation therapy is less efficient in alleviating iron accumulation in many organs, especially when iron enters the cells via specific calcium channels.

AIM

To validate our hypothesis that adding amlodipine to the iron chelation regimen is more efficient in alleviating myocardial iron overload.

METHODS

Five databases, including PubMed, Cochrane Library, Embase, ScienceDirect, and ClinicalTrials.gov, were systematically searched, and three randomized controlled trials involving 144 pediatric patients with transfusion-dependent thalassemia were included in our meta-analysis based on the predefined eligibility criteria. The quality of the included studies was assessed based on the Cochrane collaboration tool for bias assessment. The primary outcome assessed was myocardial-T2 and myocardial iron concentration, while the secondary results showed serum ferritin level, liver iron concentration, and treatment adverse outcomes. Weighted mean difference and odds ratio were calculated to measure the changes in the estimated treatment effects.

RESULTS

During the follow-up period, Amlodipine treatment significantly improved cardiac T2 by 2.79 ms compared to the control group [95% confidence interval (CI): 0.34-5.24, P = 0.03, I2 = 0%]. Additionally, a significant reduction of 0.31 in myocardial iron concentration was observed with amlodipine treatment compared to the control group [95%CI: -0.38-(-0.25), P < 0.00001, I2 = 0%]. Liver iron concentration was slightly lower in the amlodipine group by -0.04 mg/g, but this difference was not statistically significant (95%CI: -0.33-0.24, P = 0.77, I2 = 0%). Amlodipine also showed a non-significant trend toward a reduction in serum ferritin levels (-328.86 ng/mL, 95%CI: -1212.34-554.62, P = 0.47, I2 = 90%). Regarding safety, there were no significant differences between the groups in the incidence of gastrointestinal upset, hypotension, or lower limb edema.

CONCLUSION

Amlodipine with iron chelation therapy significantly improved cardiac parameters, including cardiac-T2 and myocardial iron, in patients with transfusion-dependent thalassemia without causing significant adverse events but enhancing the efficacy of iron chelation therapy.

Keywords: Amlodipine; Cardiomyopathy; Iron overload; Randomized controlled trials; Thalassemia

Core Tip: Thalassemia is the most common inherited blood disorder caused by genetic mutations that significantly reduce or abolish normal hemoglobin production altogether. Iron chelation therapy, which aims to maintain safe iron levels, eliminate deposited iron, and promptly reverse the failing heart condition, is the current treatment for iron overload in thalassemia. Our systematic review and meta-analysis attempts to establish evidence from the reported randomized controlled trials that amlodipine can effectively alleviate cardiotoxicity related to iron overload in thalassemia major patients, especially when combined with iron chelators.