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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...
Autores principales: | , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Korean Diabetes Association
2022
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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 |
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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 |
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