Role of bempedoic acid in clinical practice
Author(s)
Type
Journal Article
Abstract
Many patients do not achieve optimal low-density lipoprotein cholesterol (LDL-C) levels with statins alone; others are unable to tolerate statin therapy. Additional non-statin treatment options including ezetimibe, proprotein convertase subtilisin/kexin type 9 inhibitors, and bile acid sequestrants are often necessary to further reduce the risk of atherosclerotic cardiovascular disease. This review provides practical guidance as to the use of bempedoic acid to lower LDL-C and includes direction as to which patients may benefit and advice for safety monitoring during treatment. Bempedoic acid, a new class of agent, is a prodrug converted to bempedoyl-CoA by very long-chain acyl-CoA synthetase 1, an enzyme with high expression in the liver but that is undetectable in the skeletal muscle. Bempedoic acid inhibits the enzyme adenosine triphosphate (ATP)-citrate lyase, which lies two steps upstream from β-hydroxy β-methylglutaryl-CoA reductase in the cholesterol biosynthesis pathway. In clinical trials conducted in patients with or at risk for atherosclerotic cardiovascular disease or familial heterozygous hypercholesterolemia, bempedoic acid in combination with statins and/or ezetimibe significantly reduced LDL-C, apolipoprotein B, and high-sensitivity C-reactive protein compared with placebo. Bempedoic acid is generally well tolerated with no clinically meaningful increase in muscle-related symptoms relative to placebo, even in patients taking maximally tolerated statins. A small increase in serum uric acid (mean increase 0.8 mg/dL) is the most noteworthy adverse effect. Bempedoic acid provides an effective and generally well-tolerated medication to further reduce LDL-C in patients taking maximally tolerated statins or manage LDL-C levels in those who are unable to take statins. The potential for a reduced incidence of major cardiovascular events with bempedoic acid is being investigated in the CLEAR Outcomes trial, with results expected in 2023.
Date Issued
2021-08-01
Date Acceptance
2021-01-19
Citation
Cardiovascular Drugs and Therapy, 2021, 35 (4), pp.853-864
ISSN
0920-3206
Publisher
Springer
Start Page
853
End Page
864
Journal / Book Title
Cardiovascular Drugs and Therapy
Volume
35
Issue
4
Copyright Statement
© Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/.
License URL
Identifier
https://www.ncbi.nlm.nih.gov/pubmed/33818688
PII: 10.1007/s10557-021-07147-5
Subjects
ACTIVATED PROTEIN-KINASE
Atherosclerotic cardiovascular disease
ATP-citrate lyase
ATP-CITRATE-LYASE
Bempedoic acid
Cardiac & Cardiovascular Systems
Cardiovascular System & Cardiology
DENSITY-LIPOPROTEIN CHOLESTEROL
EFFICACY
HEALTH
HIGH-RISK
High-sensitivity C-reactive protein
Hypercholesterolemia
Life Sciences & Biomedicine
Low-density lipoprotein cholesterol
METAANALYSIS
Pharmacology & Pharmacy
SAFETY
Science & Technology
STATIN USE
TENDON-RUPTURE
Publication Status
Published
Coverage Spatial
United States
Date Publish Online
2021-04-05