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Review
. 2021 Nov 1:10:2021-8-3.
doi: 10.7573/dic.2021-8-3. eCollection 2021.

New and emerging lipid-modifying drugs to lower LDL cholesterol

Constantine E Kosmas  1   2 , Dafni Pantou  3 , Andreas Sourlas  4 , Evangelia J Papakonstantinou  5 , Rogers Echavarria Uceta  2 , Eliscer Guzman  1   2
Affiliations
Review

New and emerging lipid-modifying drugs to lower LDL cholesterol

Constantine E Kosmas et al. Drugs Context. .

Abstract

Cardiovascular disease (CVD) represents the leading cause of death worldwide. The role of low-density lipoprotein-cholesterol (LDL-C) in the pathophysiology of atherosclerosis and CVD has been well recognized. Statins are the standard of care for the management of hypercholesterolaemia, and their effectiveness in lowering LDL-C and reducing CVD risk in both primary and secondary prevention has been well established. However, several patients fail to attain optimal LDL-C goals or are intolerant to statins, especially at high doses. PCSK9 inhibitors, bempedoic acid, inclisiran, ANGPTL3 inhibitors, PPARβ/δ agonists and LXR agonists are novel or upcoming LDL-C-lowering agents that have shown promising beneficial results. This review aims to present and discuss the current clinical and scientific data pertaining to the new and emerging lipid-modifying LDL-C-lowering drugs.

Keywords: ANGPTL3 inhibitors; LDL-C-lowering; LXR agonists; PCSK9 inhibitors; PPARβ/δ agonists; bempedoic acid; cardiovascular disease; inclisiran.

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Conflict of interest statement

Disclosure and potential conflicts of interest: Constantine E. Kosmas and Eliscer Guzman have served as members of the Dyslipidemia Speaker Bureau of Amgen, Inc. The International Committee of Medical Journal Editors (ICMJE) Potential Conflicts of Interests form for the authors is available for download at: https://www.drugsincontext.com/wp-content/uploads/2021/10/dic.2021-8-3-COI.pdf

Figures

Figure 1
Figure 1
Mechanism of action of statins and bempedoic acid. ACL, adenosine triphosphate-citrate lyase; CoA, coenzyme A; HMG, 3-hydroxy-3-methylglutaryl.
Figure 2
Figure 2
Mechanism of action of PCSK9 inhibitors, inclisiran, PPARβ/δ agonists and LXR agonists. LDL-C, low-density lipoprotein cholesterol; LDLR, LDL receptors; LXR, liver X receptors; mRNA, messenger RNA; PCSK9, proprotein convertase subtilisin/kexin type 9; PPAR, peroxisome proliferator-activated receptors; RISC, RNA-induced silencing complexes; siRNA, small interfering RNA.
Figure 3
Figure 3
Mechanism of action of ANGPTL3 inhibitors. ANGPTL3, angiopoietin-like protein 3; EL, endothelial lipase; LPL, lipoprotein lipase; VLDL, very low-density lipoprotein.
See this image and copyright information in PMC

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