The selective peroxisome proliferator-activated receptor alpha modulator (SPPARMα) paradigm: Conceptual framework and therapeutic potential
Journal
Cardiovascular Diabetology
Journal Volume
18
Journal Issue
1
Pages
71
Date Issued
2019
Author(s)
Fruchart J.-C.
Santos R.D.
Aguilar-Salinas C.
Aikawa M.
Al Rasadi K.
Amarenco P.
Barter P.J.
Ceska R.
Corsini A.
Despr?s J.-P.
Duriez P.
Eckel R.H.
Ezhov M.V.
Farnier M.
Ginsberg H.N.
Hermans M.P.
Ishibashi S.
Karpe F.
Kodama T.
Koenig W.
Krempf M.
Lim S.
Lorenzatti A.J.
McPherson R.
Nu?ez-Cortes J.M.
Nordestgaard B?.G.
Ogawa H.
Packard C.J.
Plutzky J.
Ponte-Negretti C.I.
Pradhan A.
Ray K.K.
Reiner Z.
Ridker P.M.
Ruscica M.
Sadikot S.
Shimano H.
Sritara P.
Stock J.K.
Susekov A.V.
Tartar A.
Taskinen M.-R.
Tenenbaum A.
Tokg?zo?lu L.S.
Tomlinson B.
Tybj?rg-Hansen A.
Valensi P.
Vrabl?k M.
Wahli W.
Watts G.F.
Yamashita S.
Yokote K.
Zambon A.
Libby P.
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. ? 2019 The Author(s).
Subjects
Atherogenic dyslipidemia; Diabetes; Inflammation; Pemafibrate (K-877); PROMINENT; Remnant cholesterol; Residual cardiovascular risk; Selective peroxisome proliferator-activated receptor alpha modulator; SPPARMalpha; Triglycerides; Visceral obesity
SDGs
Other Subjects
high density lipoprotein cholesterol; peroxisome proliferator activated receptor alpha agonist; triacylglycerol; (R)-2-(3-((benzoxazol-2-yl-d4 (3-(4-methoxyphenoxy-d7)propyl)amino)methyl)phenoxy) butanoic acid; antilipemic agent; benzoxazole derivative; biological marker; butyric acid derivative; lipid; peroxisome proliferator activated receptor alpha; PPARA protein, human; atherogenesis; cardiometabolic risk; cardiovascular risk; conceptual framework; coronary artery atherosclerosis; disease association; disease exacerbation; drug efficacy; drug safety; dyslipidemia; high risk patient; human; lipoprotein metabolism; non insulin dependent diabetes mellitus; nonalcoholic fatty liver; population research; preclinical study; prevalence; Review; risk factor; risk reduction; treatment outcome; treatment planning; triacylglycerol blood level; animal; blood; cardiovascular disease; consensus; dyslipidemia; metabolism; molecularly targeted therapy; patient safety; risk assessment; signal transduction; Animals; Benzoxazoles; Biomarkers; Butyrates; Cardiovascular Diseases; Consensus; Dyslipidemias; Humans; Hypolipidemic Agents; Lipids; Molecular Targeted Therapy; Patient Safety; PPAR alpha; Risk Assessment; Risk Factors; Signal Transduction; Treatment Outcome
Publisher
BioMed Central Ltd.
Type
review