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Vol 81, No 2 (2023)
Review paper
Published online: 2023-01-28
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PCSK9 inhibitors and reduction in cardiovascular events: Current evidence and future perspectives

Stephen J Nicholls12
DOI: 10.33963/KP.a2023.0030
·
Pubmed: 36739653
·
Kardiol Pol 2023;81(2):115-122.
Affiliations
  1. Victorian Heart Institute, Monash University, Melbourne, Australia
  2. Monash Cardiovascular Research Center, Clayton, Australia

open access

Vol 81, No 2 (2023)
Review article
Published online: 2023-01-28

Abstract

Proprotein convertase subtilisin/kexin type 9 (PCSK9) plays an important role in low-density lipoprotein (LDL) metabolism. Pharmacological PCSK9 inhibitors have been developed as a novel approach to treating dyslipidemia. This article reviews the spectrum of evidence implicating the role of PCSK9 in lipid metabolism and the clinical impact of PCSK9 inhibitors on lipid parameters and cardiovascular risk. Biochemical and genomic studies have established the role that PCSK9 plays in lipid metabolism and potential protection from cardiovascular disease observed in the setting of PCSK9 deficiency. This led to the development of inhibitory monoclonal antibodies (evolocumab, alirocumab) that produce dose-dependent lowering of LDL cholesterol up to 60%, with evidence of regression and stabilization of coronary atherosclerosis (GLAGOV, HUYGENS, PACMAN-AMI) and reduction in cardiovascular risk in large clinical outcomes trials (FOURIER, ODYSSEY Outcomes). More recent developments have witnessed alternative approaches to PCSK9 inhibition such as RNA interference (inclisiran), vaccines, and gene editing, which are currently undergoing clinical evaluation. PCSK9 inhibition has emerged as an important component of treatment approaches to lowering LDL cholesterol and plays an increasing role in preventive strategies.

Abstract

Proprotein convertase subtilisin/kexin type 9 (PCSK9) plays an important role in low-density lipoprotein (LDL) metabolism. Pharmacological PCSK9 inhibitors have been developed as a novel approach to treating dyslipidemia. This article reviews the spectrum of evidence implicating the role of PCSK9 in lipid metabolism and the clinical impact of PCSK9 inhibitors on lipid parameters and cardiovascular risk. Biochemical and genomic studies have established the role that PCSK9 plays in lipid metabolism and potential protection from cardiovascular disease observed in the setting of PCSK9 deficiency. This led to the development of inhibitory monoclonal antibodies (evolocumab, alirocumab) that produce dose-dependent lowering of LDL cholesterol up to 60%, with evidence of regression and stabilization of coronary atherosclerosis (GLAGOV, HUYGENS, PACMAN-AMI) and reduction in cardiovascular risk in large clinical outcomes trials (FOURIER, ODYSSEY Outcomes). More recent developments have witnessed alternative approaches to PCSK9 inhibition such as RNA interference (inclisiran), vaccines, and gene editing, which are currently undergoing clinical evaluation. PCSK9 inhibition has emerged as an important component of treatment approaches to lowering LDL cholesterol and plays an increasing role in preventive strategies.

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Keywords

cardiovascular risk, clinical trials, lipids, PCSK9, prevention

About this article
Title

PCSK9 inhibitors and reduction in cardiovascular events: Current evidence and future perspectives

Journal

Kardiologia Polska (Polish Heart Journal)

Issue

Vol 81, No 2 (2023)

Article type

Review paper

Pages

115-122

Published online

2023-01-28

Page views

737

Article views/downloads

288

DOI

10.33963/KP.a2023.0030

Pubmed

36739653

Bibliographic record

Kardiol Pol 2023;81(2):115-122.

Keywords

cardiovascular risk
clinical trials
lipids
PCSK9
prevention

Authors

Stephen J Nicholls

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