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Inclisiran, Low-Density Lipoprotein Cholesterol and Lipoprotein (a).

作者信息

Katsiki Niki, Vrablik Michal, Banach Maciej, Gouni-Berthold Ioanna

机构信息

Department of Nutritional Sciences and Dietetics, International Hellenic University, 574 00 Thessaloniki, Greece.

School of Medicine, European University Cyprus, Nicosia 2404, Cyprus.

出版信息

Pharmaceuticals (Basel). 2023 Apr 12;16(4):577. doi: 10.3390/ph16040577.


DOI:10.3390/ph16040577
PMID:37111334
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10143414/
Abstract

Dyslipidemia treatment is of major importance in reducing the risk of atherosclerotic cardiovascular disease (ASCVD), which is still the most common cause of death worldwide. During the last decade, a novel lipid-lowering drug category has emerged, i.e., proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors. Apart from the two available anti-PCSK9 monoclonal antibodies (alirocumab and evolocumab), other nucleic acid-based therapies that inhibit or "silence" the expression of PCSK9 are being developed. Among them, inclisiran is the first-in-class small interfering RNA (siRNA) against PCSK9 that has been approved by both the US Food and Drug Administration (FDA) and the European Medicines Agency (EMA) for the treatment of hypercholesterolemia. Importantly, inclisiran therapy may improve low-density lipoprotein cholesterol (LDL-C) target achievement by offering a prolonged and significant LDL-C-lowering effect with the administration of only two doses per year. The present narrative review discusses the clinical trial program that has been designed to investigate the impact of inclisiran on atherogenic lipoproteins and major adverse cardiac events in different patient populations. The results of the completed clinical trials are presented, focusing on the effects of inclisiran on LDL-C and lipoprotein (a) (Lp(a)) levels as well as on other lipid parameters such as apolipoprotein B and non-high-density lipoprotein cholesterol (non-HDL-C). Ongoing clinical trials with inclisiran are also discussed.

摘要
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3856/10143414/26f896d8931b/pharmaceuticals-16-00577-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3856/10143414/26f896d8931b/pharmaceuticals-16-00577-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3856/10143414/26f896d8931b/pharmaceuticals-16-00577-g001.jpg

相似文献

[1]
Inclisiran, Low-Density Lipoprotein Cholesterol and Lipoprotein (a).

Pharmaceuticals (Basel). 2023-4-12

[2]
Inclisiran: A Novel Agent for Lowering Apolipoprotein B-containing Lipoproteins.

J Cardiovasc Pharmacol. 2021-8-1

[3]
Effect of an siRNA Therapeutic Targeting PCSK9 on Atherogenic Lipoproteins: Prespecified Secondary End Points in ORION 1.

Circulation. 2018-9-25

[4]
Proprotein convertase subtilisn/kexin type 9 inhibitors and small interfering RNA therapy for cardiovascular risk reduction: A systematic review and meta-analysis.

PLoS One. 2023

[5]
Inclisiran: A Review in Hypercholesterolemia.

Am J Cardiovasc Drugs. 2023-3

[6]
Pooled Patient-Level Analysis of Inclisiran Trials in Patients With Familial Hypercholesterolemia or Atherosclerosis.

J Am Coll Cardiol. 2021-3-9

[7]
New Strategies for Lowering Low Density Lipoprotein Cholesterol for Cardiovascular Disease Prevention.

Curr Cardiovasc Risk Rep. 2022-9

[8]
Low-density Lipoprotein-Cholesterol Lowering Strategies for Prevention of Atherosclerotic Cardiovascular Disease: Focus on siRNA Treatment Targeting PCSK9 (Inclisiran).

Curr Cardiol Rep. 2020-10-21

[9]
Harnessing RNA Interference for Cholesterol Lowering: The Bench-to-Bedside Story of Inclisiran.

J Am Heart Assoc. 2024-3-19

[10]
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Expert Opin Investig Drugs. 2018-3

引用本文的文献

[1]
Non-traditional lipid biomarkers in atherosclerotic cardiovascular disease: pathophysiological mechanisms and strategies to address residual risk.

Front Endocrinol (Lausanne). 2025-7-10

[2]
Glycolysis hijacked: a novel pathogenic role of lipoprotein(a) in valve disease.

Eur Heart J Open. 2025-6-6

[3]
Elevated lipoprotein(a) and its association with early-onset myocardial infarction and coronary burden.

Arch Cardiol Mex. 2025

[4]
Lp(a)-Lowering Agents in Development: A New Era in Tackling the Burden of Cardiovascular Risk?

Pharmaceuticals (Basel). 2025-5-19

[5]
Lipoprotein(a): Assessing the Current Knowledge and Gaps in Screening and Treatment-A Narrative Review.

J Cardiovasc Dev Dis. 2025-4-26

[6]
Lipoprotein (a) levels and clinical decision-making: data from a Mexican cohort at a tertiary medical institution.

Lipids Health Dis. 2025-5-26

[7]
2024: The year in cardiovascular disease - the year of lipoprotein(a). Research advances and new findings.

Arch Med Sci. 2025-2-22

[8]
Lipoprotein(a)-Lowering Drugs: A Mini Review.

J Clin Med Res. 2025-4

[9]
Inclisiran in Cardiovascular Health: A Review of Mechanisms, Efficacy, and Future Prospects.

Med Sci Monit. 2025-4-13

[10]
Expert opinion on the integration of combination therapy into the treatment algorithm for the management of dyslipidaemia: the integration of ezetimibe and bempedoic acid may enhance goal attainment.

Eur Heart J Cardiovasc Pharmacother. 2025-7-7

本文引用的文献

[1]
Long-term efficacy and safety of inclisiran in patients with high cardiovascular risk and elevated LDL cholesterol (ORION-3): results from the 4-year open-label extension of the ORION-1 trial.

Lancet Diabetes Endocrinol. 2023-2

[2]
Efficacy and Safety of Inclisiran in Patients with Polyvascular Disease: Pooled, Post Hoc Analysis of the ORION-9, ORION-10, and ORION-11 Phase 3 Randomized Controlled Trials.

Cardiovasc Drugs Ther. 2024-6

[3]
Inclisiran and cardiovascular events: a patient-level analysis of phase III trials.

Eur Heart J. 2023-1-7

[4]
Effect of inclisiran on lipids in primary prevention: the ORION-11 trial.

Eur Heart J. 2022-12-21

[5]
PCSK9 Inhibition: From Current Advances to Evolving Future.

Cells. 2022-9-23

[6]
PCSK9 Inhibitor Wars: How Does Inclisiran Fit in with Current Monoclonal Antibody Inhibitor Therapy? Considerations for Patient Selection.

Curr Cardiol Rep. 2022-11

[7]
PCSK9 Monoclonal Antibodies: New Developments and Their Relevance in a Nucleic Acid-Based Therapy Era.

Curr Atheroscler Rep. 2022-10

[8]
Which patients at risk of cardiovascular disease might benefit the most from inclisiran? Polish experts' opinion. The compromise between EBM and possibilities in healthcare.

Arch Med Sci. 2022-3-17

[9]
2021 ESC Guidelines on cardiovascular disease prevention in clinical practice: Developed by the Task Force for cardiovascular disease prevention in clinical practice with representatives of the European Society of Cardiology and 12 medical societies With the special contribution of the European Association of Preventive Cardiology (EAPC).

Rev Esp Cardiol (Engl Ed). 2022-5

[10]
Pharmacokinetics and pharmacodynamics of inclisiran, a small interfering RNA therapy, in patients with hepatic impairment.

J Clin Lipidol. 2022

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