The selective peroxisome proliferator-activated receptor alpha modulator (SPPARMα) paradigm: Conceptual framework and therapeutic potential: A consensus statement from the International Atherosclerosis Society (IAS) and the Residual Risk Reduction Initiative (R3i) Foundation
Author(s)
Type
Journal Article
Abstract
In the era of precision medicine, treatments that target specific modifiable characteristics of high-risk patients have the potential to lower further the residual risk of atherosclerotic cardiovascular events. Correction of atherogenic dyslipidemia, however, remains a major unmet clinical need. Elevated plasma triglycerides, with or without low levels of high-density lipoprotein cholesterol (HDL-C), offer a key modifiable component of this common dyslipidemia, especially in insulin resistant conditions such as type 2 diabetes mellitus. The development of selective peroxisome proliferator-activated receptor alpha modulators (SPPARMα) offers an approach to address this treatment gap. This Joint Consensus Panel appraised evidence for the first SPPARMα agonist and concluded that this agent represents a novel therapeutic class, distinct from fibrates, based on pharmacological activity, and, importantly, a safe hepatic and renal profile. The ongoing PROMINENT cardiovascular outcomes trial is testing in 10,000 patients with type 2 diabetes mellitus, elevated triglycerides, and low levels of HDL-C whether treatment with this SPPARMα agonist safely reduces residual cardiovascular risk.
Date Issued
2019-06-04
Date Acceptance
2019-04-29
Citation
Cardiovascular Diabetology, 2019, 18
ISSN
1475-2840
Publisher
BioMed Central
Journal / Book Title
Cardiovascular Diabetology
Volume
18
Copyright Statement
© 2019 The Author(s). Open Access. This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
Identifier
https://www.ncbi.nlm.nih.gov/pubmed/31164165
PII: 10.1186/s12933-019-0864-7
Subjects
Atherogenic dyslipidemia
Diabetes
Inflammation
PROMINENT
Pemafibrate (K-877)
Remnant cholesterol
Residual cardiovascular risk
SPPARMalpha
Selective peroxisome proliferator-activated receptor alpha modulator
Triglycerides
Visceral obesity
Publication Status
Published
Coverage Spatial
England
Article Number
71