New targets and mechanisms of action for lipid-lowering and anti-inflammatory therapies in atherosclerosis: where does the field stand?

ABSTRACT

Introduction

Atherosclerotic cardiovascular disease remains a leading cause of morbidity and mortality worldwide, despite widespread use of statins. There is a need to develop additional therapeutic strategies that will complement statins to achieve more effective reductions in cardiovascular risk.

Areas covered

This review provides a comprehensive summary of current areas of therapeutic development targeting both lipid and inflammatory factors implicated in the pathogenesis of atherosclerosis. In addition to develop of novel approaches that will produce more effective lowering of low-density lipoprotein cholesterol, clinical trials are currently evaluating the potential to target other atherogenic lipid parameters such as triglyceride-rich lipoproteins and Lp(a), in addition to promoting the biological properties of high-density lipoproteins. Targeting inflammation within the vascular wall has emerged as a new frontier in cardiovascular prevention, with early evidence that use of anti-inflammatory agents have the potential to reduce cardiovascular risk.

Expert opinion

Clinical practice has an increasing array of therapeutic tools to achieve more effective lowering of low-density lipoprotein cholesterol for high-risk patients. In addition, clinical trials have the potential to deliver a range of additional agents to the clinic, that target alternative lipid and inflammatory mediators. This will permit the potential to personalize cardiovascular prevention.

KEYWORDS:

• Atherosclerosis
• risk factors
• therapies
• clinical trials
• prevention

Article highlights

• Atherosclerotic cardiovascular disease remains a leading cause of morbidity and mortality worldwide.

• Beyond use of statins, recent developments in dyslipidemia therapeutics provide new approaches to lowering levels of LDL cholesterol, while opening up new areas targeting triglyceride-rich lipoproteins and Lp(a).

• Inflammation-targeted therapies focusing on the NLRP3 inflammasome and associated cytokines have the potential to further reduce the residual clinical risk in statin-treated patients.

Declaration of interest

SJ Nicholls has received research support from AstraZeneca, Amgen, Anthera, CSL Behring, Cerenis, Eli Lilly, Esperion, Resverlogix, New Amsterdam Pharma, Novartis, InfraReDx and Sanofi-Regeneron and is a consultant for Amgen, Akcea, Arrowhead, AstraZeneca, Boehringer Ingelheim, CSL Behring, Eli Lilly, Esperion, Kowa, Merck, Takeda, Pfizer, Sanofi- Regeneron, Vaxxinity, CSL Sequiris, Cyclarity and Novo Nordisk. The authors have no other 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 apart from those disclosed.

Reviewer disclosures

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

Additional information

Funding

This paper was not funded.