Efficacy and safety of calcium channel blockers in preventing cardiac siderosis in thalassemia patients: An updated <scp>meta‐analysis</scp> with trial sequential analysis

Soliman, Youssef; Abdelaziz, Ahmed; Mouffokes, Adel; Amer, Basma E; Goudy, Yomna Mohamed; Abdelwahab, Omar Ahmed; Badawy, Marwa M; Diab, Rehab Adel; Elsharkawy, Asmaa

doi:10.1111/ejh.13919

Cited by 3 publications

(2 citation statements)

References 32 publications

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“…Rash, Renal disorders, Gastrointestinal problems [118] There are currently many other iron chelators that show great promise towards mitigating iron overload, like Deferitazole and SP-420 [119,120]. Amlodipine, a calcium channel blocker, has been reported to be efficient in decreasing myocardial iron concentration and significantly elevating cardiac T2*, which indicates its role for the treatment of cardiac iron overload [121]. Furthermore, a recently discovered novel erythroid maturation agent, luspatercept, has been reported to lower the serum ferritin levels in adult β-thalassemic patients, as well as significantly reduce the number of blood transfusions (>33%) in TDT patients (BELIEVE trial) [122].…”

Section: Adverse Effectsmentioning

confidence: 99%

Understanding the Intricacies of Iron Overload Associated with β-Thalassemia: A Comprehensive Review

Basu

Rahaman

Dolai

et al. 2023

Thalassemia Reports

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β-thalassemia, a congenital genetic hematological disorder characterized by the decrease or absence of β-globin chains, leads to a decrease in levels of Hemoglobin A. The affected individuals can be categorized into two cohorts based on transfusion dependency: transfusion-dependent thalassemia (TDT) and non-transfusion-dependent thalassemia (NTDT). Remarkably, despite the primary pathology lying in β-globin chain depletion, β-thalassemia also exhibits an intriguing association with iron overload. Iron metabolism, a tightly regulated physiological process, reveals a complex interplay in these patients. Over time, both cohorts of β-thalassemic individuals develop iron overload, albeit through distinct mechanisms. Addressing the diverse complications that arise due to iron overload in β-thalassemic patients, the utilization of iron chelators has gained a lot of significance. With varying efficacies, routes of administration, and modes of action, different iron chelators offer unique benefits to patients. In the Indian context, three commercialized iron chelators have emerged, showcasing a high adherence rate to iron chelator-based treatment regimens among β-thalassemic individuals. In this review, we explore the intriguing connection between β-thalassemia and iron overload, shedding light on the intricate mechanisms at play. We delve into the intricacies of iron metabolism, unveiling the distinct pathways leading to iron accumulation in these patients. Additionally, the therapeutic efficacy of different iron chelators in managing iron overload complications is mentioned briefly, along with the guidelines for their usage in India. Through this comprehensive analysis, we aim to deepen our understanding of β-thalassemia and iron overload, paving the way for optimized treatment strategies. Ultimately, our findings provide valuable insights into improving the care and outcomes of individuals affected by β-thalassemia.

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Section: Adverse Effectsmentioning

confidence: 99%

Understanding the Intricacies of Iron Overload Associated with β-Thalassemia: A Comprehensive Review

Basu

Rahaman

Dolai

et al. 2023

Thalassemia Reports

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“…A meta-analysis [19] on three randomized controlled trials (n = 130 patients) unveiled a non-significant difference in serum ferritin between amlodipine and control groups, with a weighted mean difference (WMD) of −0.16, and 95% confidence interval (CI) −0.51 to 0.19. Moreover, a recent systematic review found that amlodipine can significantly improve cardiac T2-weighted magnetic resonance imaging (MRI T2*) and myocardial iron concentration (MIC) and even reduce the incidence of cardiomyopathy-related iron overload in thalassemia patients without significant side effects [20]. The values of Hedges' g for cardiac MRI T2* and MIC were 0.36, 95% CI 0.10-0.62 and −0.82, 95% CI −1.40 to −0.24, respectively.…”

Section: Introductionmentioning

confidence: 99%

Amlodipine Therapy in β-Thalassemia Patients: A Systematic Review and Meta-Analysis on Ferritin Levels and Liver MRI T2*

Aliasgharian,

Karami,

Zahedi

et al. 2023

Thalassemia Reports

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Background and aim: We conducted a review to determine the efficacy of amlodipine alongside iron chelators on serum ferritin levels and liver T2-weighted magnetic resonance imaging (MRI T2*) in β-thalassemia patients. Methods: Systematic search was conducted in multiple databases, including Web of Science, PubMed, Scopus, Embase, Cochrane Library, ClinicalTrials.gov, the Iranian Registry of Clinical Trials (IRCT), ProQuest, OpenGrey, and Web of Science Conference Proceedings Citation Index. The search was closed in January 2023. Primary outcomes were comprised of liver MRI T2* (millisecond (msec)) and serum ferritin levels (ng/mL). Results: Seven studies (n = 227) were included in the study. The pooled Cohen’s d for serum ferritin was estimated at −0.46, 95% confidence interval (CI) −1.11 to 0.19 and p = 0.16 (I2 86.23%, p < 0.0001). The pooled mean difference for serum ferritin was −366.44 ng/mL, 95% CI −844.94 to 112.05, and p = 0.13 (I2 81.63%, p < 0.0001). After a meta-regression based on the length of using amlodipine, a coefficient for the mean difference was also −23.23 ng/mL and 95% CI −155.21 to 108.75. The coefficient obtained from a meta-regression as per the amlodipine dose at 5 mg/day than 2.5 to 5 mg/day anchored at −323.49 ng/mL and 95% CI −826.14 to 1473.12. A meta-regression according to the baseline values of serum ferritin discovered a coefficient of 1.25 ng/mL and 95% CI 0.15 to 2.35. Based on two included studies (n = 96), the overall Cohen’s d for liver MRI T2* was 2.069, 95% CI −0.896 to 5.035, and p = 0.17 (I2 96.31%, p< 0.0001). The synthesized mean difference for liver MRI T2* was 8.76 msec, 95% CI −4.16 to 21.67, and p = 0.18 (I2 98.38%, p < 0.000). Conclusion: At a very low level of evidence, probably using amlodipine at a dose of 2.5 to 5 mg a day, up to a year, alongside iron chelators slightly decreases serum ferritin levels in iron-overloaded thalassemia cases by nearly 366 ng/mL (23 ng/mL per month). The liver MRI T2* might also rise to 8.76 msec upon co-therapy with amlodipine.

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Ebselen: A promising therapy protecting cardiomyocytes from excess iron in iron-overloaded thalassemia patients

et al. 2023

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Iron-overload-associated cardiomyopathy has been one of the primary causes of mortality in thalassemia patients with iron burden. There is growing evidence citing the beneficial effects of ebselen as an antioxidant selectively blocking the divalent metal transporter 1 (DMT-1) to deter iron ingress into cardiomyocytes, raising internets in viewing this component in this population in order to treat and even prevent cardiomyopathy occurring from iron surplus. In this article, we reviewed the potential advantageous effects of ebselen in thalassemia patients who suffer from iron excess, susceptible to cardiomyopathy induced by iron overload. A systematic search in several databases, including PubMed, Scopus, and Web of Science, was conducted to explore the role of ebselen in controlling iron-overload-related cardiomyopathy in thalassemia patients by the keywords of Ebselen AND iron. The inclusion criteria were English-written preclinical and clinical studies investigating the efficacy and side effects of ebselen in an iron-overload context. After searching the databases, 44 articles were found. Next, of 19 published articles, 3 were included in this article. After reviewing the references of the included studies, no articles were added. In conclusion ebselen can be a promising adjuvant therapy in patients with thalassemia alongside the standard treatment with iron chelators, particularly in severe cases with cardiomyopathy, due to falling iron inflow by inhibiting DMT-1 and increasing ferroportin-1 expression and antioxidant properties. However, clinical studies need to be carried out to reach a definite conclusion.

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Efficacy and safety of calcium channel blockers in preventing cardiac siderosis in thalassemia patients: An updated meta‐analysis with trial sequential analysis

Cited by 3 publications

References 32 publications

Understanding the Intricacies of Iron Overload Associated with β-Thalassemia: A Comprehensive Review

Understanding the Intricacies of Iron Overload Associated with β-Thalassemia: A Comprehensive Review

Amlodipine Therapy in β-Thalassemia Patients: A Systematic Review and Meta-Analysis on Ferritin Levels and Liver MRI T2*

Ebselen: A promising therapy protecting cardiomyocytes from excess iron in iron-overloaded thalassemia patients

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