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Cited by 44Lipoproteins and Cardiovascular HealthLipid metabolism and disordersCholesterol and Lipid Metabolism

Low-density Lipoprotein-Cholesterol Lowering Strategies for Prevention of Atherosclerotic Cardiovascular Disease: Focus on siRNA Treatment Targeting PCSK9 (Inclisiran)

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Sinning, David, Landmesser, Ulf·2020·Current Cardiology Reports
DOI 10.1007/s11886-020-01427-6PMC PMC7578129
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Abstract

PURPOSE OF REVIEW: The aim of low-density lipoprotein-cholesterol (LDL-C) lowering therapies is to safely achieve a consistent and long-term reduction in exposure of the vasculature to atherogenic lipoproteins in order to reduce the risk of atherosclerotic cardiovascular (CV) disease and the associated CV events, such as myocardial infarctions and ischemic strokes. This review summarizes the concept and clinical development of a novel molecular approach to efficiently lower LDL-C, a synthetic small interfering ribonucleic acid (siRNA)-inclisiran-directed against proprotein convertase subtilisin-kexin type 9 (PCSK9). RECENT FINDINGS: The understanding of genes regulating atherogenic lipoproteins and their causal role in the development of atherosclerotic CV disease has substantially advanced over the past years. This has opened the possibility for development of molecular therapies targeting these atherogenic lipoproteins, in particular by RNA-targeted treatment approaches. The most advanced clinical development program is the siRNA-treatment targeting PCSK9 (inclisiran), involving more than 4000 patients in clinical studies. Phase 1 and 2 studies have identified the dose of 300 mg inclisiran for efficient LDL-C lowering. Most recently, three phase 3 studies demonstrated that a regimen of inclisiran every 6 months was feasible and reduced LDL-C by approximately 50% in patients at high or very high CV risk or with familial hypercholesterolemia. Adverse events were similar in the inclisiran and the placebo groups, except for more frequent transient injection site reactions with inclisiran than with placebo. siRNA therapy targeting PCSK9 (inclisiran) applied twice a year efficiently reduced LDL-C by approximately 50% and was safe in recent phase 3 studies. The effects of this treatment on CV outcome are currently further assessed in a large ongoing CV outcome trial.

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Authors
Sinning, D., & Landmesser, U.
Affiliations
  • Charité – Universitätsmedizin Berlin (DE)
  • German Centre for Cardiovascular Research (DE)
Corresponding author
Landmesser, Ulf
ORCID
Venue
Current Cardiology Reports
Publisher
Springer Science and Business Media LLC
Published
2020-10-21
Volume
22
Issue
12
Pages
176-176
ISSN
  • 1523-3782 (ISSN-L)
  • 1534-3170
DOI
10.1007/s11886-020-01427-6
PMC
PMC7578129
OpenAlex
W3093906897
Cited by
44
References
50
Citations by year
2026: 7 · 2025: 4 · 2024: 8 · 2023: 6 · 2022: 7 · 2021: 10 · 2020: 2
FWCI
1.42
Type
journal article
Language
en
Open access
Licence
Locations
  • Current Cardiology Reports (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • Informationszentrum Lebenswissenschaften (ZB MED) (submittedVersion, cc-by)
  • Refubium (Universitätsbibliothek der Freien Universität Berlin) (submittedVersion, cc-by)
  • Universitätsbibliothek der FU Berlin Hochschulschriftenstelle u. Dokumentenserver (cc-by)
Funders
Charité
Topics
  • Health Sciences › Medicine › Surgery › Lipoproteins and Cardiovascular Health
  • Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Lipid metabolism and disorders
  • Health Sciences › Medicine › Surgery › Cholesterol and Lipid Metabolism
Keywords
inclisiran, PCSK9, siRNA therapeutics, LDL cholesterol lowering, atherosclerotic cardiovascular disease, familial hypercholesterolemia, atherogenic lipoproteins, RNA-targeted therapeutics, cardiovascular risk reduction, injection site reactions
MeSH terms
Proprotein Convertase 9, Anticholesteremic Agents, Cardiovascular Diseases, Humans, Cholesterol, LDL, RNA, Small Interfering

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