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Current Atherosclerosis Reports
Published in: Current Atherosclerosis Reports 1/2021

Open Access 01-01-2021 | Fenofibrate | Statin Drugs (R. Ceska, Section Editor)

Selective Peroxisome Proliferator-Activated Receptor Alpha Modulators (SPPARMα) in the Metabolic Syndrome: Is Pemafibrate Light at the End of the Tunnel?

Authors: Jean-Charles Fruchart, Michel P. Hermans, Jamila Fruchart-Najib, Tatsuhiko Kodama

Published in: Current Atherosclerosis Reports | Issue 1/2021

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Abstract

Purpose of Review

Adoption of poor lifestyles (inactivity and energy-dense diets) has driven the worldwide increase in the metabolic syndrome, type 2 diabetes mellitus and non-alcoholic steatohepatitis (NASH). Of the defining features of the metabolic syndrome, an atherogenic dyslipidaemia characterised by elevated triglycerides (TG) and low plasma concentration of high-density lipoprotein cholesterol is a major driver of risk for atherosclerotic cardiovascular disease. Beyond lifestyle intervention and statins, targeting the nuclear receptor peroxisome proliferator-activated receptor alpha (PPARα) is a therapeutic option. However, current PPARα agonists (fibrates) have limitations, including safety issues and the lack of definitive evidence for cardiovascular benefit. Modulating the ligand structure to enhance binding at the PPARα receptor, with the aim of maximising beneficial effects and minimising adverse effects, underlies the SPPARMα concept.

Recent Findings

This review discusses the history of SPPARM development, latterly focusing on evidence for the first licensed SPPARMα, pemafibrate. Evidence from animal models of hypertriglyceridaemia or NASH, as well as clinical trials in patients with atherogenic dyslipidaemia, are overviewed.

Summary

The available data set the scene for therapeutic application of SPPARMα in the metabolic syndrome, and possibly, NASH. The outstanding question, which has so far eluded fibrates in the setting of current evidence-based therapy including statins, is whether treatment with pemafibrate significantly reduces cardiovascular events in patients with atherogenic dyslipidaemia. The PROMINENT study in patients with type 2 diabetes mellitus and this dyslipidaemia is critical to evaluating this.
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Metadata
Title
Selective Peroxisome Proliferator-Activated Receptor Alpha Modulators (SPPARMα) in the Metabolic Syndrome: Is Pemafibrate Light at the End of the Tunnel?
Authors
Jean-Charles Fruchart
Michel P. Hermans
Jamila Fruchart-Najib
Tatsuhiko Kodama
Publication date
01-01-2021
Publisher
Springer US
Published in
Current Atherosclerosis Reports / Issue 1/2021
Print ISSN: 1523-3804
Electronic ISSN: 1534-6242
DOI
https://doi.org/10.1007/s11883-020-00897-x

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10-04-2024 Myocardial Infarction News

» View more highlights on the ACC 2024 congress hub page

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