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Cited by 34Lipoproteins and Cardiovascular HealthCholesterol and Lipid MetabolismLipid metabolism and disorders

Efficacy and safety of inclisiran a newly approved FDA drug: a systematic review and pooled analysis of available clinical studies

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Cicero, Arrigo F.G., Fogacci, Federica, Zambon, Alberto, Toth, Peter P., Borghi, Claudio·2022·American Heart Journal Plus: Cardiology Research and Practice
DOI 10.1016/j.ahjo.2022.100127PMC PMC10978220
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Abstract

Study objective: This systematic review and meta-analysis aimed to assess the efficacy and safety profile of treatment with inclisiran, a drug that has been recently approved by the United States Food and Drug Administration (FDA) and the European Medicines Agency (EMA). Design: A systematic literature search was conducted in order to identify randomized controlled trials (RCTs) assessing the effect on lipoproteins and the safety profile of inclisiran. Results: Data were pooled from 5 RCTs, which included 4226 subjects. Meta-analyses of data suggested that the multiple-dose regimens of inclisiran yielded a significant reduction in serum levels of proprotein convertase subtilisin/kexin type 9 (MD = -78.23%, 95%CI: -86.74, -69.71) and low-density lipoprotein cholesterol (MD = -45.48%, 95%CI: -50.36%, -40.61%) throughout the studies. Furthermore, treatment with inclisiran significantly affected total cholesterol (MD = -13.67%, 95%CI: -20.78%, -6.57%), high-density lipoprotein cholesterol (MD = 8.29%, 95%CI: 4.66%,11.93%), non-HDL cholesterol (MD = -39.45%, 95%CI: -43.6%, -35.31%), apolipoprotein B (MD = -34.58%, 95%CI: -38.78%, -30.78%) and lipoprotein(a) (MD = -20.9%, 95%CI: -25.8%, -15.99%). Multiple-dose regimens of inclisiran were associated with increased risk of injection-site reactions (any reaction: OR = 5.86, 95%CI: 3.44, 9.98; mild reactions: OR = 5.19, 95%CI: 1.68, 16.07; moderate reactions: OR = 13.37, 95%CI: 3.17, 56.46), and bronchitis (OR = 1.58, 95%CI: 1.10, 2.26), while the incidence of the pre-specified exploratory CV endpoint significantly decreased at 18 months (OR = 0.74, 95%CI: 0.58, 0.94). Conclusion and relevance: Inclisiran has favourable effects on serum lipid levels and an acceptable safety profile. Further well-designed RCTs are needed to explore its longer-term safety.

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  • Many patients stop taking daily statin medications or PCSK9 antibody injections irregularly, reducing their ability to prevent cardiovascular diseases.

    “Clinical observations demonstrate that numerous patients stop taking their daily statin medications or PCSK9 antibody injections irregularly which reduces their ability to prevent cardiovascular diseases [44, 80].”

    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 [80]

    The Discussion says poor long-term adherence can prevent patients from reaching LDL-C goals and contribute to residual cardiovascular risk. It does not report clinical observations that numerous patients stop daily statins or take PCSK9 antibody injections irregularly; it describes adherence to PCSK9 inhibitors as already acceptable. Page numbers are unavailable in our copy. (LLM, conf=0.85)

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Authors
Cicero, A. F. G., Fogacci, F., Zambon, A., Toth, P. P., & Borghi, C.
Affiliations
  • IRCCS Azienda Ospedliero-Universitaria di Bologna Policlinico di Sant'Orsola (IT)
  • University of Padua (IT)
  • Johns Hopkins University (US)
Corresponding author
Cicero, Arrigo F.G.
ORCID
Venue
American Heart Journal Plus: Cardiology Research and Practice
Publisher
Elsevier BV
Published
2022-01
Volume
13
Pages
100127
ISSN
2666-6022 (ISSN-L)
DOI
10.1016/j.ahjo.2022.100127
PMC
PMC10978220
OpenAlex
W4223912855
Cited by
34
References
44
Citations by year
2026: 3 · 2025: 12 · 2024: 7 · 2023: 10 · 2022: 2
FWCI
1.90
Type
journal article
Language
en
Open access
Licence
Locations
  • American Heart Journal Plus Cardiology Research and Practice (publishedVersion, cc-by-nc-nd)
  • PubMed Central (publishedVersion, cc-by-nc-nd)
  • PubMed (publishedVersion)
  • Archivio istituzionale della ricerca (Alma Mater Studiorum Università di Bologna) (submittedVersion, cc-by-nc-nd)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
  • Padua Research Archive (University of Padova) (submittedVersion, cc-by-nc-nd)
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 inhibitors, LDL cholesterol lowering, lipoprotein(a), apolipoprotein B, non-HDL cholesterol, HDL cholesterol, total cholesterol, injection site reactions, bronchitis, drug safety, hypercholesterolemia, lipid-lowering therapy, FDA approval, European Medicines Agency approval, multiple-dose regimen

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