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Cited by 120Lipoproteins and Cardiovascular HealthCholesterol and Lipid MetabolismLipid metabolism and disorders

Inclisiran—New hope in the management of lipid disorders?

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Dyrbuś, Krzysztof, Gąsior, Mariusz, Penson, Peter, Ray, Kausik K., Banach, Maciej·2020·Journal of Clinical Lipidology
DOI 10.1016/j.jacl.2019.11.001
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Abstract

Drugs reducing plasma concentrations of apolipoprotein B-containing lipoproteins have been demonstrated to reduce the risk of cardiovascular disease (CVD) in both primary and secondary prevention. Despite the demonstrated efficacy of statins and ezetimibe on low-density lipoprotein (LDL) concentration and long-term CVD risk, a large number of patients do not achieve their therapeutic goals. The introduction of monoclonal antibodies against proprotein convertase subtilisin/kexin type 9 (PCSK9) protein was a milestone in the treatment of lipid disorders, as their administration leads to unprecedentedly low LDL cholesterol concentrations. Inclisiran represents an entirely new mechanism of PSCK9 protein inhibition in hepatocytes, targeting the messenger RNA for PCSK9. Its administration is necessary only every 3 to 6 months, which is an essential advantage over statin and monoclonal antibody therapy. The infrequent administration regimen can increase the number of patients who maintain their therapeutic goals, especially in patients struggling to comply with daily or biweekly pharmacotherapy. Preclinical studies and Phase I and Phase II clinical trials of inclisiran have demonstrated its tolerability and efficacy in promoting long-term reduction of both PCSK9 protein and LDL cholesterol. The efficacy and safety of inclisiran will continue to be assessed in ongoing and forthcoming trials on larger patient groups. If the results of these trials reflect previously published data, they will add further evidence that inclisiran might be a revolutionary new tool in the pharmacologic management of plasma lipids. This review summarizes the currently available literature data on inclisiran with respect to its mechanism of action, effectiveness, and safety as a lipid-lowering drug for CVD prevention.

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  • Rare hepatotoxicity, myopathy, or renal toxicity events were observed, and no concerning trends emerged from routine laboratory tests.

    “Rare hepatotoxicity or myopathy or renal toxicity events were observed and no concerning trends emerged from routine laboratory tests [82, 83].”

    From Inclisiran SiRNA therapy for durable LDL-C reduction: a systematic review and meta-analysis highlighting a breakthrough in long-term cardiovascular risk management (2026) · cites this paper as [83]

    The Drug safety section (page not provided) reports one asymptomatic elevation of liver enzymes, which the cited study’s authors associated with concurrent atorvastatin, and lists musculoskeletal pain among reported adverse effects. It does not identify those events as hepatotoxicity or myopathy, report renal toxicity events, or assess trends across routine laboratory tests. (LLM, conf=0.84)

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Cited by

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Authors
Dyrbuś, K., Gąsior, M., Penson, P., Ray, K. K., & Banach, M.
Affiliations
  • Medical University of Silesia (PL)
  • Liverpool John Moores University (GB)
  • Imperial College London (GB)
  • Medical University of Lodz (PL)
Corresponding author
Dyrbuś, Krzysztof
ORCID
Venue
Journal of Clinical Lipidology
Publisher
Elsevier BV
Published
2020-01
Volume
14
Issue
1
Pages
16-27
ISSN
  • 1876-4789 (ISSN-L)
  • 1933-2874
DOI
10.1016/j.jacl.2019.11.001
OpenAlex
W2987162559
Cited by
120
References
11
Citations by year
2026: 1 · 2025: 8 · 2024: 17 · 2023: 18 · 2022: 26 · 2021: 28 · 2020: 22
FWCI
3.97
Type
journal article
Language
en
Open access
Licence
Locations
  • Journal of clinical lipidology (publishedVersion)
  • PubMed (publishedVersion)
  • Liverpool John Moores University (acceptedVersion)
Topics
  • Health Sciences › Medicine › Surgery › Lipoproteins and Cardiovascular Health
  • Health Sciences › Medicine › Surgery › Cholesterol and Lipid Metabolism
  • Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Lipid metabolism and disorders
Keywords
inclisiran, PCSK9 inhibition, PCSK9 monoclonal antibodies, lipid-lowering therapy, LDL cholesterol lowering, apolipoprotein B-containing lipoproteins, cardiovascular disease prevention, statins, ezetimibe, drug safety and tolerability
MeSH terms
Ezetimibe, Proprotein Convertase 9, PCSK9 Inhibitors, Apolipoproteins B, Humans, Cholesterol, LDL, Hydroxymethylglutaryl-CoA Reductase Inhibitors, Hepatocytes, RNA, Small Interfering, Lipid Metabolism Disorders

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