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Bempedoic Acid and Ezetimibe for the Treatment of Hypercholesterolemia: A Systematic Review and Meta-Analysis of Randomized Phase II/III trials

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A Letter to the Editor to this article was published on 07 April 2021

Abstract

Background and Objective

A limited number of trials have evaluated the efficacy of a fixed-dose combination of bempedoic acid and ezetimibe for the treatment of hypercholesterolemia. The aim of this meta-analysis of existing studies was to evaluate the efficacy and safety of fixed-dose bempedoic acid and ezetimibe combination therapy for the treatment of hypercholesterolemia.

Methods

A systematic literature search was conducted to identify randomized controlled trials (RCTs) comparing bempedoic acid and ezetimibe, versus placebo or ezetimibe alone, to 30 August 2020. A meta-analysis was conducted to investigate the efficacy of bempedoic acid and ezetimibe on lipid parameters and highly sensitive C-reactive protein (hsCRP) levels in patients with hypercholesterolemia or established atherosclerotic cardiovascular disease (ASCVD). Mean differences (MDs) or relative risk (RR) with their corresponding 95% confidence intervals (CIs), using random-effects models, were used to provide pooled estimates.

Results

A total of three phase II and III RCTs, comprising 388 patients, of whom 49.2% were treated with bempedoic acid and ezetimibe, and 197 controls, were identified. The duration of treatment was 12 weeks. Bempedoic acid and ezetimibe significantly reduced low-density lipoprotein cholesterol (MD − 29.14%, 95% CI − 39.52 to − 18.76; p < .001), total cholesterol (MD − 15.78%, 95% CI − 20.84 to − 10.72; p = 0.01), non-high-density lipoprotein cholesterol (MD − 18.36%, 95% CI − 24.60 to − 12.12; p = 0.01), and hsCRP levels (MD − 30.48%, 95% CI − 44.69 to − 16.28; p = 0.04). No significant effects on triglycerides (MD − 8.35%, 95% CI − 16.08 to − 0.63; p = 0.72) and improvement in high-density lipoprotein cholesterol (MD 1.63%, 95% CI − 4.03 to 7.28; p = 0.92) were observed with the fixed-dose combination therapy. Regarding safety, bempedoic acid and ezetimibe combination was associated with a non-significant increased risk of drug-related adverse events (RR 1.61, 95% CI 0.86–2.35) and overall adverse events (RR 1.16. 95% CI 0.97–1.35); however, the incidence of discontinuation of therapy (RR 0.75, 95% CI 0.35–1.49) was lower.

Conclusion

This review found bempedoic acid and ezetimibe significantly lowered lipid parameters, attenuated hsCRP levels, and had an acceptable safety profile for the treatment of hypercholesterolemia and ASCVD.

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Acknowledgements

The authors would like to acknowledge Dr. Wafa Ali Aldhaleei for providing support in reviewing this manuscript. The authors also wish to extent their thanks to the editor of Clinical Drug Investigation and two anonymous referees who kindly reviewed the earlier version of this manuscript and provided valuable feedback.

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Authors and Affiliations

  1. Department of Internal Medicine, College of Medicine and Health Sciences, UAE University, Al Ain, UAE

    Akshaya Srikanth Bhagavathula

  2. Department of Cardiology, Sheikh Shakhbout Medical City, Abu Dhabi, UAE

    Nadya Obaid Al Matrooshi

  3. Centre for Intelligent Healthcare, Coventry University, Coventry, CV1 5FB, UK

    Cain C. T. Clark

  4. Department of Community Nutrition, Student Research Committee, Faculty of Nutrition and Food Technology, National Nutrition and Food Technology Research Institute, Shahid Beheshti University of Medical Sciences, Tehran, Iran

    Jamal Rahmani

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  1. Akshaya Srikanth Bhagavathula
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Correspondence to Akshaya Srikanth Bhagavathula.

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Funding

No funding was used to prepare this review.

Conflict of interest

Akshaya Srikanth Bhagavathula, Nadya Obaid Al Matrooshi, Cain CT Clark, and Jamal Rahmani declare no conflicts of interest.

Ethical approval

Ethical approval is not required for this systematic review and meta-analysis as this was only a secondary analysis of data that are already available in scientific databases.

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Data availability

The data underlying this article will be shared upon reasonable request to the corresponding author.

Author contributions

The authors’ responsibilities were as follows: ASB and JR designed the study and independently carried out the literature search and screening of articles; JR and ASB analyzed the data; ASB and CC wrote the first draft of the manuscript; NOA performed the re-analysis of the data, critically reviewed the literature, and revised the manuscript. All authors read and approved the final paper.

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Bhagavathula, A.S., Al Matrooshi, N.O., Clark, C.C.T. et al. Bempedoic Acid and Ezetimibe for the Treatment of Hypercholesterolemia: A Systematic Review and Meta-Analysis of Randomized Phase II/III trials. Clin Drug Investig 41, 19–28 (2021). https://doi.org/10.1007/s40261-020-00989-1

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