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
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
UR - http://www.scopus.com/inward/record.url?scp=85066822428&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85066822428&partnerID=8YFLogxK
U2 - 10.1186/s12933-019-0864-7
DO - 10.1186/s12933-019-0864-7
M3 - Review article
C2 - 31164165
AN - SCOPUS:85066822428
VL - 18
JO - Cardiovascular Diabetology
JF - Cardiovascular Diabetology
SN - 1475-2840
IS - 1
M1 - 71
ER -