Bempedoic Acid: a cholesterol lowering agent with a novel mechanism of action

ABSTRACT

Introduction

Dyslipidemia is a common condition that increases the risk of heart diseases and stroke. High levels of low-density lipoprotein-cholesterol (LDL-C) are correlated with a higher risk for heart disease. A drug class known as ‘statins’ is the gold standard for LDL-C-lowering, but its use in some patients is limited by its adverse effects of myalgias and myopathies. Use of other LDL-C-lowering agents is frequently limited by cost and degree of efficacy. Additionally, many high-risk atherosclerotic cardiovascular disease patients fail to meet LDL-C goals despite maximally tolerated statin therapy with or without the addition of a non-statin agent.

Areas Covered

This review covers the pharmacology, pharmacokinetics, clinical trials, and clinical implications of bempedoic acid. A PubMed search was conducted using the terms bempedoic, bempedoic acid, Nexletol, ETC-1002, and adenosine triphosphate citrate lyase inhibitor. Additional data were obtained from the prescribing information and relevant guidelines. All clinical trials were included.

Expert Opinion

Bempedoic acid has not been shown to cause myalgias or myopathies and is likely to be competitively affordable compared to other LDL-C-lowering agents. Bempedoic acid has been shown to be superior compared to placebo and provides additional LDL-C lowering on top of maximally tolerated statin therapy or combined with ezetimibe alone.

KEYWORDS:

• Bempedoic acid
• etc-1002
• nexletol
• cholesterol
• ldl
• ascvd
• hyperlipidemia
• dyslipidemia
• pharmacology
• metabolic agents

Article highlights

• Bempedoic acid is a cholesterol-lowering agent with a novel mechanism of action that works by inhibiting adenosine triphosphate citrate lyase, an enzyme upstream of 3-hydroxy-3-methyl-glutaryl-CoA (HMG-CoA) reductase, the target of statins.

• Bempedoic acid has not been shown to cause the myalgias and myopathies commonly associated with statins.

• It presents an additional option for efficacious LDL-C lowering in patients with high risk atherosclerotic cardiovascular disease (ASCVD) that have a statin intolerance or fail to meet LDL-C goals despite maximally tolerated statin therapy.

• In several phase III clinical trials and meta-analyses, bempedoic acid was shown to have a favorable safety profile.

• Results from clinical trials and meta-analyses also show that bempedoic acid significantly reduces high sensitivity-c-reactive protein (hs-CRP), suggesting it may improve cardiovascular outcomes.

• Patients that received bempedoic acid also had a lower incidence of new onset or worsening diabetes mellitus compared to controls.

Declaration of interest

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Additional information

Funding

This paper was not funded