TY - JOUR
T1 - The selective peroxisome proliferator-activated receptor alpha modulator (SPPARMα) paradigm
T2 - Conceptual framework and therapeutic potential
AU - Fruchart, Jean Charles
AU - Santos, Raul D.
AU - Aguilar-Salinas, Carlos
AU - Aikawa, Masanori
AU - Al Rasadi, Khalid
AU - Amarenco, Pierre
AU - Barter, Philip J.
AU - Ceska, Richard
AU - Corsini, Alberto
AU - Després, Jean Pierre
AU - Duriez, Patrick
AU - Eckel, Robert H.
AU - Ezhov, Marat V.
AU - Farnier, Michel
AU - Ginsberg, Henry N.
AU - Hermans, Michel P.
AU - Ishibashi, Shun
AU - Karpe, Fredrik
AU - Kodama, Tatsuhiko
AU - Koenig, Wolfgang
AU - Krempf, Michel
AU - Lim, Soo
AU - Lorenzatti, Alberto J.
AU - McPherson, Ruth
AU - Nuñez-Cortes, Jesus Millan
AU - Nordestgaard, Børge G.
AU - Ogawa, Hisao
AU - Packard, Chris J.
AU - Plutzky, Jorge
AU - Ponte-Negretti, Carlos I.
AU - Pradhan, Aruna
AU - Ray, Kausik K.
AU - Reiner, Zeljko
AU - Ridker, Paul M.
AU - Ruscica, Massimiliano
AU - Sadikot, Shaukat
AU - Shimano, Hitoshi
AU - Sritara, Piyamitr
AU - Stock, Jane K.
AU - Su, Ta Chen
AU - Susekov, Andrey V.
AU - Tartar, André
AU - Taskinen, Marja Riitta
AU - Tenenbaum, Alexander
AU - Tokgözoǧlu, Lale S.
AU - Tomlinson, Brian
AU - Tybjærg-Hansen, Anne
AU - Valensi, Paul
AU - Vrablík, Michal
AU - Wahli, Walter
AU - Watts, Gerald F.
AU - Yamashita, Shizuya
AU - Yokote, Koutaro
AU - Zambon, Alberto
AU - Libby, Peter
N1 - Funding Information:
The Consensus Panel members met at a closed expert meeting in Chantilly, France in November 2018 where evidence relating to SPPARMα was critically appraised and discussed. Support for travel was provided by an academic Grant from the R3i. There were no other sources of funding.
Publisher Copyright:
© 2019 The Author(s).
PY - 2019/6/4
Y1 - 2019/6/4
N2 - 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.
AB - 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.
KW - Atherogenic dyslipidemia
KW - Diabetes
KW - Inflammation
KW - Pemafibrate (K-877)
KW - PROMINENT
KW - Remnant cholesterol
KW - Residual cardiovascular risk
KW - Selective peroxisome proliferator-activated receptor alpha modulator
KW - SPPARMalpha
KW - Triglycerides
KW - Visceral obesity
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U2 - 10.1186/s12933-019-0864-7
DO - 10.1186/s12933-019-0864-7
M3 - Review article
C2 - 31164165
AN - SCOPUS:85066822428
SN - 1475-2840
VL - 18
JO - Cardiovascular Diabetology
JF - Cardiovascular Diabetology
IS - 1
M1 - 71
ER -