Cargando…

New, Novel Lipid-Lowering Agents for Reducing Cardiovascular Risk: Beyond Statins

Statins are the cornerstone of the prevention and treatment of atherosclerotic cardiovascular disease (ASCVD). However, even under optimal statin therapy, a significant residual ASCVD risk remains. Therefore, there has been an unmet clinical need for novel lipid-lowering agents that can target low-d...

Descripción completa

Detalles Bibliográficos
Autores principales: Kim, Kyuho, Ginsberg, Henry N., Choi, Sung Hee
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Korean Diabetes Association 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9353557/
https://www.ncbi.nlm.nih.gov/pubmed/35929170
http://dx.doi.org/10.4093/dmj.2022.0198
_version_ 1784762890407903232
author Kim, Kyuho
Ginsberg, Henry N.
Choi, Sung Hee
author_facet Kim, Kyuho
Ginsberg, Henry N.
Choi, Sung Hee
author_sort Kim, Kyuho
collection PubMed
description Statins are the cornerstone of the prevention and treatment of atherosclerotic cardiovascular disease (ASCVD). However, even under optimal statin therapy, a significant residual ASCVD risk remains. Therefore, there has been an unmet clinical need for novel lipid-lowering agents that can target low-density lipoprotein cholesterol (LDL-C) and other atherogenic particles. During the past decade, several drugs have been developed for the treatment of dyslipidemia. Inclisiran, a small interfering RNA that targets proprotein convertase subtilisin/kexin type 9 (PCSK9), shows comparable effects to that of PCSK9 monoclonal antibodies. Bempedoic acid, an ATP citrate lyase inhibitor, is a valuable treatment option for the patients with statin intolerance. Pemafibrate, the first selective peroxisome proliferator-activated receptor alpha modulator, showed a favorable benefit-risk balance in phase 2 trial, but the large clinical phase 3 trial (PROMINENT) was recently stopped for futility based on a late interim analysis. High dose icosapent ethyl, a modified eicosapentaenoic acid preparation, shows cardiovascular benefits. Evinacumab, an angiopoietin-like 3 (ANGPTL3) monoclonal antibody, reduces plasma LDL-C levels in patients with refractory hypercholesterolemia. Novel antisense oligonucleotides targeting apolipoprotein C3 (apoC3), ANGPTL3, and lipoprotein(a) have significantly attenuated the levels of their target molecules with beneficial effects on associated dyslipidemias. Apolipoprotein A1 (apoA1) is considered as a potential treatment to exploit the athero-protective effects of high-density lipoprotein cholesterol (HDL-C), but solid clinical evidence is necessary. In this review, we discuss the mode of action and clinical outcomes of these novel lipid-lowering agents beyond statins.
format Online
Article
Text
id pubmed-9353557
institution National Center for Biotechnology Information
language English
publishDate 2022
publisher Korean Diabetes Association
record_format MEDLINE/PubMed
spelling pubmed-93535572022-08-11 New, Novel Lipid-Lowering Agents for Reducing Cardiovascular Risk: Beyond Statins Kim, Kyuho Ginsberg, Henry N. Choi, Sung Hee Diabetes Metab J Review Statins are the cornerstone of the prevention and treatment of atherosclerotic cardiovascular disease (ASCVD). However, even under optimal statin therapy, a significant residual ASCVD risk remains. Therefore, there has been an unmet clinical need for novel lipid-lowering agents that can target low-density lipoprotein cholesterol (LDL-C) and other atherogenic particles. During the past decade, several drugs have been developed for the treatment of dyslipidemia. Inclisiran, a small interfering RNA that targets proprotein convertase subtilisin/kexin type 9 (PCSK9), shows comparable effects to that of PCSK9 monoclonal antibodies. Bempedoic acid, an ATP citrate lyase inhibitor, is a valuable treatment option for the patients with statin intolerance. Pemafibrate, the first selective peroxisome proliferator-activated receptor alpha modulator, showed a favorable benefit-risk balance in phase 2 trial, but the large clinical phase 3 trial (PROMINENT) was recently stopped for futility based on a late interim analysis. High dose icosapent ethyl, a modified eicosapentaenoic acid preparation, shows cardiovascular benefits. Evinacumab, an angiopoietin-like 3 (ANGPTL3) monoclonal antibody, reduces plasma LDL-C levels in patients with refractory hypercholesterolemia. Novel antisense oligonucleotides targeting apolipoprotein C3 (apoC3), ANGPTL3, and lipoprotein(a) have significantly attenuated the levels of their target molecules with beneficial effects on associated dyslipidemias. Apolipoprotein A1 (apoA1) is considered as a potential treatment to exploit the athero-protective effects of high-density lipoprotein cholesterol (HDL-C), but solid clinical evidence is necessary. In this review, we discuss the mode of action and clinical outcomes of these novel lipid-lowering agents beyond statins. Korean Diabetes Association 2022-07 2022-07-27 /pmc/articles/PMC9353557/ /pubmed/35929170 http://dx.doi.org/10.4093/dmj.2022.0198 Text en Copyright © 2022 Korean Diabetes Association https://creativecommons.org/licenses/by-nc/4.0/This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (https://creativecommons.org/licenses/by-nc/4.0/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Review
Kim, Kyuho
Ginsberg, Henry N.
Choi, Sung Hee
New, Novel Lipid-Lowering Agents for Reducing Cardiovascular Risk: Beyond Statins
title New, Novel Lipid-Lowering Agents for Reducing Cardiovascular Risk: Beyond Statins
title_full New, Novel Lipid-Lowering Agents for Reducing Cardiovascular Risk: Beyond Statins
title_fullStr New, Novel Lipid-Lowering Agents for Reducing Cardiovascular Risk: Beyond Statins
title_full_unstemmed New, Novel Lipid-Lowering Agents for Reducing Cardiovascular Risk: Beyond Statins
title_short New, Novel Lipid-Lowering Agents for Reducing Cardiovascular Risk: Beyond Statins
title_sort new, novel lipid-lowering agents for reducing cardiovascular risk: beyond statins
topic Review
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9353557/
https://www.ncbi.nlm.nih.gov/pubmed/35929170
http://dx.doi.org/10.4093/dmj.2022.0198
work_keys_str_mv AT kimkyuho newnovellipidloweringagentsforreducingcardiovascularriskbeyondstatins
AT ginsberghenryn newnovellipidloweringagentsforreducingcardiovascularriskbeyondstatins
AT choisunghee newnovellipidloweringagentsforreducingcardiovascularriskbeyondstatins