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Cited by 56Lipoproteins and Cardiovascular HealthCholesterol and Lipid MetabolismBlood Pressure and Hypertension Studies

Network meta-analysis of randomized trials evaluating the comparative efficacy of lipid-lowering therapies added to maximally tolerated statins for the reduction of low-density lipoprotein cholesterol

Open access
Toth, Peter P., Bray, Sarah, Villa, Guillermo, Palagashvili, Tamara, Sattar, Naveed, Stroes, Erik S. G., Worth, Gavin M.·2022·Journal of the American Heart Association
DOI 10.1161/jaha.122.025551PMC PMC9683660
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Abstract

Background Lowering low-density lipoprotein cholesterol (LDL-C) levels decreases major cardiovascular events and is recommended for patients at elevated cardiovascular risk. However, appropriate doses of statin therapy are often insufficient to reduce LDL-C in accordance with current guidelines. In such cases, treatment could be supplemented with nonstatin lipid-lowering therapy. Methods and Results A systematic literature review and network meta-analysis were conducted on randomized controlled trials of nonstatin lipid-lowering therapy added to maximally tolerated statins, including statin-intolerant patients. The primary objective was to assess relative efficacy of nonstatin lipid-lowering therapy in reducing LDL-C levels at week 12. Secondary objectives included the following: LDL-C level reduction at week 24 and change in non-high-density lipoprotein cholesterol and apolipoprotein B at week 12. There were 48 randomized controlled trials included in the primary network meta-analysis. All nonstatin agents significantly reduced LDL-C from baseline versus placebo, regardless of background therapy. At week 12, evolocumab, 140 mg every 2 weeks (Q2W)/420 mg once a month, and alirocumab, 150 mg Q2W, were the most efficacious regimens, followed by alirocumab, 75 mg Q2W, alirocumab, 300 mg once a month, inclisiran, bempedoic acid/ezetimibe fixed-dose combination, and ezetimibe and bempedoic acid used as monotherapies. Primary end point results were generally consistent at week 24, and for other lipid end points at week 12. Conclusions Evolocumab, 140 mg Q2W/420 mg once a month, and alirocumab, 150 mg Q2W, were consistently the most efficacious nonstatin regimens when added to maximally tolerated statins to lower LDL-C, non-high-density lipoprotein cholesterol, and apolipoprotein B levels and facilitate attainment of guideline-recommended risk-stratified lipoprotein levels.

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Crossref · 10.1161/jaha.122.025551

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  • The addition of PCSK9 monoclonal antibodies evolocumab and alirocumab to maximum tolerated doses of statin therapy in participants at high risk for ASCVD demonstrated an average reduction in LDL cholesterol ranging from 52% to 65%.

    “The addition of the PCSK9 monoclonal antibodies evolocumab and alirocumab to maximum tolerated doses of statin therapy in participants who were at high risk for ASCVD demonstrated an average reduction in LDL cholesterol ranging from 52% to 65% (120,121).”

    From 10. Cardiovascular Disease and Risk Management: Standards of Care in Diabetes—2026 (2026) · cites this paper as [121]

    The Results section (Primary Objective: Placebo-Corrected LDL-C Reduction at Week 12; page unavailable) reports substantial reductions with both antibodies: 62.80% for evolocumab, 64.80% for alirocumab 150 mg, and 53.97% for alirocumab 75 mg in a subgroup of trials whose populations were predominantly, not entirely, patients with ASCVD. This supports the general magnitude of the claimed range, but does not establish a 52% lower endpoint for these antibodies or that all participants were at high risk for ASCVD. (LLM, conf=0.83)

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Research works printed but not linked: 3

  1. [28]Canadian Agency for Drugs and Technologies in Health. CADTH peer review checklist for search strategies. CADTH; 2013. Available at: https://www.cadth.ca/sites/default/files/is/Peer_review/CADTH%20Peer%20Review%20Checklist%20for%20Search%20Strategies_e.pdf. Accessed April 8, 2022.
  2. [97]Teramoto T, Kobayashi M, Uno K, Takagi Y, Matsuoka O, Sugimoto M, Inoue S, Minami F, Baccara‐Dinet MT. Efficacy and safety of alirocumab in Japanese patients with hypercholesterolemia on stable statin therapy: first data with the 75 mg every two weeks dose. Circulation. 2014; 130: A13651.
  3. [99]ClinicalTrials.gov. Goal achievement after utilizing an anti‐PCSK9 antibody in statin intolerant subjects‐4 (GAUSS‐4). Available at: https://clinicaltrials.gov/show/nct02634580. Accessed April 8, 2022. PMC6490723 26946077

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Authors
Toth, P. P., Bray, S., Villa, G., Palagashvili, T., Sattar, N., Stroes, E. S. G., & Worth, G. M.
Affiliations
  • Johns Hopkins University (US)
  • Amgen (United Kingdom) (GB)
  • Amgen (Switzerland) (CH)
  • Amgen (United States) (US)
  • University of Glasgow (GB)
  • University of Amsterdam (NL)
Corresponding author
Toth, Peter P.
ORCID
Venue
Journal of the American Heart Association
Publisher
Ovid Technologies (Wolters Kluwer Health)
Published
2022-09-20
Volume
11
Issue
18
Pages
e025551-e025551
ISSN
2047-9980 (ISSN-L)
DOI
10.1161/jaha.122.025551
PMC
PMC9683660
OpenAlex
W4294992476
Cited by
56
References
83
Citations by year
2026: 14 · 2025: 14 · 2024: 15 · 2023: 11 · 2022: 2
FWCI
2.49
Type
journal article
Language
en
Open access
Licence
cc-by-nc-nd
Locations
  • Journal of the American Heart Association (publishedVersion, cc-by-nc-nd)
  • PubMed Central (publishedVersion, cc-by-nc-nd)
  • PubMed (publishedVersion)
  • ENLIGHTEN (Jurnal Bimbingan dan Konseling Islam) (submittedVersion, cc-by-sa)
  • Pure Amsterdam UMC (submittedVersion, cc-by)
  • Data Archiving and Networked Services (DANS) (submittedVersion, other-oa)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion)
Funders
Amgen
Topics
  • Health Sciences › Medicine › Surgery › Lipoproteins and Cardiovascular Health
  • Health Sciences › Medicine › Surgery › Cholesterol and Lipid Metabolism
  • Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Blood Pressure and Hypertension Studies
Keywords
LDL cholesterol lowering, non-statin lipid-lowering therapy, evolocumab, alirocumab, inclisiran, bempedoic acid, ezetimibe, PCSK9 inhibitors, non-HDL cholesterol, apolipoprotein B, statin intolerance, cardiovascular risk reduction
MeSH terms
Ezetimibe, Network Meta-Analysis, Network Meta-Analysis as Topic, Anticholesteremic Agents, Apolipoproteins, Cholesterol, Dicarboxylic Acids, Double-Blind Method, Fatty Acids, Humans, Cholesterol, LDL, Randomized Controlled Trials as Topic, Treatment Outcome, Hydroxymethylglutaryl-CoA Reductase Inhibitors

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