Combinatorial approach to treat iron overload cardiomyopathy in pediatric patients with thalassemia-major: A systematic review and meta-analysis

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.