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...
| Main Authors: | , , |
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| Format: | Article |
| Language: | English |
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Korean Diabetes Association
2022-07-01
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| Series: | Diabetes & Metabolism Journal |
| Subjects: | |
| Online Access: | http://e-dmj.org/upload/pdf/dmj-2022-0198.pdf |
| _version_ | 1818537078253682688 |
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| author | Kyuho Kim Henry N. Ginsberg Sung Hee Choi |
| author_facet | Kyuho Kim Henry N. Ginsberg Sung Hee Choi |
| author_sort | Kyuho Kim |
| collection | DOAJ |
| 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. |
| first_indexed | 2024-12-11T18:46:07Z |
| format | Article |
| id | doaj.art-b520fac66df546f0b03d9b55e19e4b0a |
| institution | Directory Open Access Journal |
| issn | 2233-6079 2233-6087 |
| language | English |
| last_indexed | 2024-12-11T18:46:07Z |
| publishDate | 2022-07-01 |
| publisher | Korean Diabetes Association |
| record_format | Article |
| series | Diabetes & Metabolism Journal |
| spelling | doaj.art-b520fac66df546f0b03d9b55e19e4b0a2022-12-22T00:54:27ZengKorean Diabetes AssociationDiabetes & Metabolism Journal2233-60792233-60872022-07-0146451753210.4093/dmj.2022.01982684New, Novel Lipid-Lowering Agents for Reducing Cardiovascular Risk: Beyond StatinsKyuho Kim0Henry N. Ginsberg1Sung Hee Choi2 Department of Internal Medicine, Seoul National University Bundang Hospital, Seongnam, Korea Department of Preventive Medicine and Nutrition, Vagelos College of Physicians and Surgeons, Columbia University, New York, NY, USA Department of Internal Medicine, Seoul National University Bundang Hospital, Seongnam, KoreaStatins 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.http://e-dmj.org/upload/pdf/dmj-2022-0198.pdfangiopoietin-like protein 3apoprotein(a)apolipoprotein c-iiicardiovascular diseasesdyslipidemiaslipoprotein(a)oligonucleotidesantisensepcsk9 inhibitorsppar alphastatins |
| spellingShingle | Kyuho Kim Henry N. Ginsberg Sung Hee Choi New, Novel Lipid-Lowering Agents for Reducing Cardiovascular Risk: Beyond Statins Diabetes & Metabolism Journal angiopoietin-like protein 3 apoprotein(a) apolipoprotein c-iii cardiovascular diseases dyslipidemias lipoprotein(a) oligonucleotides antisense pcsk9 inhibitors ppar alpha 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 | angiopoietin-like protein 3 apoprotein(a) apolipoprotein c-iii cardiovascular diseases dyslipidemias lipoprotein(a) oligonucleotides antisense pcsk9 inhibitors ppar alpha statins |
| url | http://e-dmj.org/upload/pdf/dmj-2022-0198.pdf |
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