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Cited by 38Lipoproteins and Cardiovascular HealthCholesterol and Lipid MetabolismAntiplatelet Therapy and Cardiovascular Diseases

Clinical efficacy and safety outcomes of bempedoic acid for LDL-C lowering therapy in patients at high cardiovascular risk: a systematic review and meta-analysis

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Lin, Yingfeng, Parco, Claudio, Karathanos, Athanasios, Krieger, Torben, Schulze, Volker, Chernyak, Nadja, Icks, Andrea, Kelm, Malte +2 more·2022·BMJ Open
DOI 10.1136/bmjopen-2021-048893PMC PMC8883220
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Abstract

Objectives: Bempedoic acid (BA) is a novel oral low-density lipoprotein cholesterol lowering drug. This systematic review and meta-analysis aims to assess efficacy and safety for clinical outcomes in high cardiovascular (CV) risk patients. Data sources: MEDLINE, Cochrane Central Register of Controlled Trials, Google Scholar, Embase, ClinicalTrials.gov, Clinical Trial Results and the American College of Cardiology web site were searched. Study selection: Randomised controlled trials (RCTs) of BA versus placebo in high CV risk patients reporting clinical outcomes were included. Main outcomes and measures: Primary efficacy outcomes were major adverse cardiovascular events (MACE), all-cause mortality, CV mortality and non-fatal myocardial infarction (MI). Safety outcomes included new onset or worsening of diabetes mellitus (DM), muscular disorders, gout and worsening of renal function. Results: Six RCTs with a total of 3956 patients and follow-ups of four to 52 weeks were identified. Heterogeneity mainly derived from differing follow-up duration and baseline CV risk. No difference in MACE (OR 0.84; 95% CI 0.61 to 1.15), all-cause mortality (OR 2.37; CI 0.80 to 6.99) and CV mortality (OR 1.66; CI 0.45 to 6.04) for BA versus placebo was observed. BA showed beneficial trends for non-fatal MI (OR 0.57; CI 0.32 to 1.00) and was associated with a lower risk of new-onset or worsening of DM (OR 0.68; CI 0.49 to 0.94), but higher risk of gout (OR 3.29; CI 1.28 to 8.46) and a trend for muscular disorders (OR 2.60; CI 1.15 to 5.91) and worsening of renal function (OR 4.24; CI 0.98 to 18.39). Conclusion: BA in high CV risk patients showed no significant effects on major CV outcomes in short-term follow-up. Unfavourable effects on muscular disorders, renal function and gout sound a note of caution. Hence, further studies with longer term follow-up in carefully selected populations are needed to clarify the risk/benefit ratio of this novel therapy.

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  • Differences between these results and previous meta-analyses are likely attributable to lack of statistical power and imprecise estimates because CLEAR Outcomes had not yet been published at the time of the previous meta-analyses but is included in this meta-analysis.

    “These differences are likely attributable to a lack of statistical power and imprecise estimates as the largest outcomes-based trial, CLEAR Outcomes, had not yet been published at the time of the previous meta-analyses but is included in our meta-analysis [7].”

    From The Clinical Efficacy and Safety of Bempedoic Acid in Patients at Elevated Risk of Cardiovascular Disease: A Meta-Analysis of Randomized Clinical Trials (2024) · cites this paper as [19]

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  • These results contrast with the most recent meta-analysis of clinical outcomes with bempedoic acid, which found no statistically significant reductions in MACE, coronary revascularization, or unstable angina hospitalization and found a statistically significant reduction in new-onset diabetes not seen in the current analysis.

    “Our results contrast with those of the most recent meta-analysis assessing clinical outcomes with the use of BA [19]. In that meta-analysis, there were no statistically significant reductions with respect to MACE, coronary revascularization, or hospitalization for unstable angina. In addition, there was a statistically significant reduction in new-onset diabetes not seen in the current analysis.”

    From The Clinical Efficacy and Safety of Bempedoic Acid in Patients at Elevated Risk of Cardiovascular Disease: A Meta-Analysis of Randomized Clinical Trials (2024) · cites this paper as [19]

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Cited by

Sorted by citations

Authors
Lin, Y., Parco, C., Karathanos, A., Krieger, T., Schulze, V., Chernyak, N., Icks, A., Kelm, M., Brockmeyer, M., & Wolff, G.
Affiliations
Heinrich Heine University Düsseldorf (DE)
Corresponding author
Wolff, Georg
ORCID
Venue
BMJ Open
Publisher
BMJ
Published
2022-02
Volume
12
Issue
2
Pages
e048893
ISSN
2044-6055 (ISSN-L)
DOI
10.1136/bmjopen-2021-048893
PMC
PMC8883220
OpenAlex
W4221046976
Cited by
38
References
10
Citations by year
2026: 5 · 2025: 4 · 2024: 7 · 2023: 17 · 2022: 5
FWCI
1.96
Type
journal article
Language
en
Open access
Licence
Locations
  • BMJ Open (publishedVersion, cc-by-nc)
  • PubMed Central (publishedVersion, cc-by-nc)
  • PubMed (publishedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
Funders
Medical Faculty of the Heinrich Heine University Düsseldorf (No. 2018-32)
Topics
  • Health Sciences › Medicine › Surgery › Lipoproteins and Cardiovascular Health
  • Health Sciences › Medicine › Surgery › Cholesterol and Lipid Metabolism
  • Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Antiplatelet Therapy and Cardiovascular Diseases
Keywords
bempedoic acid, LDL cholesterol lowering, high cardiovascular risk, major adverse cardiovascular events, all-cause mortality, cardiovascular mortality, myocardial infarction, diabetes mellitus, gout, muscle disorders, renal function, drug safety, statin-resistant hypercholesterolemia, cardiovascular risk stratification, risk-benefit assessment, LDL-C lowering therapy
MeSH terms
Dicarboxylic Acids, Fatty Acids, Humans, Cholesterol, LDL, Treatment Outcome

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