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Cochrane Database of Systematic Reviews

Calcium channel blockers for preventing cardiomyopathy due to iron overload in people with transfusion‐dependent beta thalassaemia

Overview of attention for article published in Cochrane database of systematic reviews, November 2023
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Title
Calcium channel blockers for preventing cardiomyopathy due to iron overload in people with transfusion‐dependent beta thalassaemia
Published in
Cochrane database of systematic reviews, November 2023
DOI 10.1002/14651858.cd011626.pub3
Pubmed ID
Authors

Zahra Ali Padhani, Manesh Kumar Gangwani, Alina Sadaf, Babar Hasan, Steven Colan, Najveen Alvi, Jai K Das

Abstract

Beta-thalassaemia is an inherited blood disorder that reduces the production of haemoglobin. The most severe form requires recurrent blood transfusions, which can lead to iron overload. Cardiovascular dysfunction caused by iron overload is the leading cause of morbidity and mortality in people with transfusion-dependent beta-thalassaemia. Iron chelation therapy has reduced the severity of systemic iron overload, but removal of iron from the myocardium requires a very proactive preventive strategy. There is evidence that calcium channel blockers may reduce myocardial iron deposition. This is an update of a Cochrane Review first published in 2018. To assess the effects of calcium channel blockers plus standard iron chelation therapy, compared with standard iron chelation therapy (alone or with a placebo), on cardiomyopathy due to iron overload in people with transfusion-dependent beta thalassaemia. We searched the Cochrane Haemoglobinopathies Trials Register, compiled from electronic database searches and handsearching of journals and conference abstract books, to 13 January 2022. We also searched ongoing trials databases and the reference lists of relevant articles and reviews. We included randomised controlled trials (RCTs) of calcium channel blockers combined with standard chelation therapy versus standard chelation therapy alone or combined with placebo in people with transfusion-dependent beta thalassaemia. We used standard Cochrane methods. We used GRADE to assess certainty of evidence. We included six RCTs (five parallel-group trials and one cross-over trial) with 253 participants; there were 126 participants in the amlodipine arms and 127 in the control arms. The certainty of the evidence was low for most outcomes at 12 months; the evidence for liver iron concentration was of moderate certainty, and the evidence for adverse events was of very low certainty. Amlodipine plus standard iron chelation compared with standard iron chelation (alone or with placebo) may have little or no effect on cardiac T2* values at 12 months (mean difference (MD) 1.30 ms, 95% confidence interval (CI) -0.53 to 3.14; 4 trials, 191 participants; low-certainty evidence) and left ventricular ejection fraction (LVEF) at 12 months (MD 0.81%, 95% CI -0.92% to 2.54%; 3 trials, 136 participants; low-certainty evidence). Amlodipine plus standard iron chelation compared with standard iron chelation (alone or with placebo) may reduce myocardial iron concentration (MIC) after 12 months (MD -0.27 mg/g, 95% CI -0.46 to -0.08; 3 trials, 138 participants; low-certainty evidence). The results of our analysis suggest that amlodipine has little or no effect on heart T2*, MIC, or LVEF after six months, but the evidence is very uncertain. Amlodipine plus standard iron chelation compared with standard iron chelation (alone or with placebo) may increase liver T2* values after 12 months (MD 1.48 ms, 95% CI 0.27 to 2.69; 3 trials, 127 participants; low-certainty evidence), but may have little or no effect on serum ferritin at 12 months (MD 0.07 μg/mL, 95% CI -0.20 to 0.35; 4 trials, 187 participants; low-certainty evidence), and probably has little or no effect on liver iron concentration (LIC) after 12 months (MD -0.86 mg/g, 95% CI -4.39 to 2.66; 2 trials, 123 participants; moderate-certainty evidence). The results of our analysis suggest that amlodipine has little or no effect on serum ferritin, liver T2* values, or LIC after six months, but the evidence is very uncertain. The included trials did not report any serious adverse events at six or 12 months of intervention. The studies did report mild adverse effects such as oedema, dizziness, mild cutaneous allergy, joint swelling, and mild gastrointestinal symptoms. Amlodipine may be associated with a higher risk of oedema (risk ratio (RR) 5.54, 95% CI 1.24 to 24.76; 4 trials, 167 participants; very low-certainty evidence). We found no difference between the groups in the occurrence of other adverse events, but the evidence was very uncertain. No trials reported mortality, cardiac function assessments other than echocardiographic estimation of LVEF, electrocardiographic abnormalities, quality of life, compliance with treatment, or cost of interventions. The available evidence suggests that calcium channel blockers may reduce MIC and may increase liver T2* values in people with transfusion-dependent beta thalassaemia. Longer-term multicentre RCTs are needed to assess the efficacy and safety of calcium channel blockers for myocardial iron overload, especially in younger children. Future trials should also investigate the role of baseline MIC in the response to calcium channel blockers, and include a cost-effectiveness analysis.

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Mendeley readers

Mendeley readers

The data shown below were compiled from readership statistics for 50 Mendeley readers of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country Count As %
United States 1 2%
Unknown 49 98%

Demographic breakdown

Readers by professional status Count As %
Student > Master 5 10%
Student > Ph. D. Student 3 6%
Other 2 4%
Researcher 2 4%
Professor 2 4%
Other 3 6%
Unknown 33 66%
Readers by discipline Count As %
Medicine and Dentistry 9 18%
Biochemistry, Genetics and Molecular Biology 2 4%
Environmental Science 2 4%
Social Sciences 1 2%
Nursing and Health Professions 1 2%
Other 0 0%
Unknown 35 70%
Attention Score in Context

Attention Score in Context

This research output has an Altmetric Attention Score of 1. This is our high-level measure of the quality and quantity of online attention that it has received. This Attention Score, as well as the ranking and number of research outputs shown below, was calculated when the research output was last mentioned on 08 December 2023.
All research outputs
#23,514,286
of 26,180,352 outputs
Outputs from Cochrane database of systematic reviews
#12,857
of 13,190 outputs
Outputs of similar age
#320,944
of 384,349 outputs
Outputs of similar age from Cochrane database of systematic reviews
#87
of 87 outputs
Altmetric has tracked 26,180,352 research outputs across all sources so far. This one is in the 1st percentile – i.e., 1% of other outputs scored the same or lower than it.
So far Altmetric has tracked 13,190 research outputs from this source. They typically receive a lot more attention than average, with a mean Attention Score of 35.5. This one is in the 1st percentile – i.e., 1% of its peers scored the same or lower than it.
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We're also able to compare this research output to 87 others from the same source and published within six weeks on either side of this one. This one is in the 1st percentile – i.e., 1% of its contemporaries scored the same or lower than it.