The selective peroxisome proliferator-activated receptor alpha modulator (SPPARMα) paradigm

Conceptual framework and therapeutic potential

Jean Charles Fruchart, Raul D. Santos, Carlos Aguilar-Salinas, Masanori Aikawa, Khalid Al Rasadi, Pierre Amarenco, Philip J. Barter, Richard Ceska, Alberto Corsini, Jean Pierre Després, Patrick Duriez, Robert H. Eckel, Marat V. Ezhov, Michel Farnier, Henry N. Ginsberg, Michel P. Hermans, Shun Ishibashi, Fredrik Karpe, Tatsuhiko Kodama, Wolfgang Koenig & 35 others Michel Krempf, Soo Lim, Alberto J. Lorenzatti, Ruth McPherson, Jesus Millan Nuñez-Cortes, Børge G. Nordestgaard, Hisao Ogawa, Chris J. Packard, Jorge Plutzky, Carlos I. Ponte-Negretti, Aruna Pradhan, Kausik K. Ray, Zeljko Reiner, Paul M. Ridker, Massimiliano Ruscica, Shaukat Sadikot, Hitoshi Shimano, Piyamitr Sritara, Jane K. Stock, Ta Chen Su, Andrey V. Susekov, André Tartar, Marja Riitta Taskinen, Alexander Tenenbaum, Lale S. Tokgözoǧlu, Brian Tomlinson, Anne Tybjærg-Hansen, Paul Valensi, Michal Vrablík, Walter Wahli, Gerald F. Watts, Shizuya Yamashita, Koutaro Yokote, Alberto Zambon, Peter Libby

Research output: Contribution to journalReview articleResearchpeer-review

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.

Original languageEnglish
Article number71
JournalCardiovascular Diabetology
Volume18
Issue number1
DOIs
StatePublished - 4 Jun 2019

Fingerprint

PPAR alpha
Dyslipidemias
Type 2 Diabetes Mellitus
HDL Cholesterol
Triglycerides
Fibric Acids
Precision Medicine
Therapeutics
Joints
Pharmacology
Insulin
Kidney
Liver

Keywords

  • Atherogenic dyslipidemia
  • Diabetes
  • Inflammation
  • PROMINENT
  • Pemafibrate (K-877)
  • Remnant cholesterol
  • Residual cardiovascular risk
  • SPPARMalpha
  • Selective peroxisome proliferator-activated receptor alpha modulator
  • Triglycerides
  • Visceral obesity

Cite this

Fruchart, Jean Charles ; Santos, Raul D. ; Aguilar-Salinas, Carlos ; Aikawa, Masanori ; Al Rasadi, Khalid ; Amarenco, Pierre ; Barter, Philip J. ; Ceska, Richard ; Corsini, Alberto ; Després, Jean Pierre ; Duriez, Patrick ; Eckel, Robert H. ; Ezhov, Marat V. ; Farnier, Michel ; Ginsberg, Henry N. ; Hermans, Michel P. ; Ishibashi, Shun ; Karpe, Fredrik ; Kodama, Tatsuhiko ; Koenig, Wolfgang ; Krempf, Michel ; Lim, Soo ; Lorenzatti, Alberto J. ; McPherson, Ruth ; Nuñez-Cortes, Jesus Millan ; Nordestgaard, Børge G. ; Ogawa, Hisao ; Packard, Chris J. ; Plutzky, Jorge ; Ponte-Negretti, Carlos I. ; Pradhan, Aruna ; Ray, Kausik K. ; Reiner, Zeljko ; Ridker, Paul M. ; Ruscica, Massimiliano ; Sadikot, Shaukat ; Shimano, Hitoshi ; Sritara, Piyamitr ; Stock, Jane K. ; Su, Ta Chen ; Susekov, Andrey V. ; Tartar, André ; Taskinen, Marja Riitta ; Tenenbaum, Alexander ; Tokgözoǧlu, Lale S. ; Tomlinson, Brian ; Tybjærg-Hansen, Anne ; Valensi, Paul ; Vrablík, Michal ; Wahli, Walter ; Watts, Gerald F. ; Yamashita, Shizuya ; Yokote, Koutaro ; Zambon, Alberto ; Libby, Peter. / The selective peroxisome proliferator-activated receptor alpha modulator (SPPARMα) paradigm : Conceptual framework and therapeutic potential. In: Cardiovascular Diabetology. 2019 ; Vol. 18, No. 1.
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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.",
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author = "Fruchart, {Jean Charles} and Santos, {Raul D.} and Carlos Aguilar-Salinas and Masanori Aikawa and {Al Rasadi}, Khalid and Pierre Amarenco and Barter, {Philip J.} and Richard Ceska and Alberto Corsini and Despr{\'e}s, {Jean Pierre} and Patrick Duriez and Eckel, {Robert H.} and Ezhov, {Marat V.} and Michel Farnier and Ginsberg, {Henry N.} and Hermans, {Michel P.} and Shun Ishibashi and Fredrik Karpe and Tatsuhiko Kodama and Wolfgang Koenig and Michel Krempf and Soo Lim and Lorenzatti, {Alberto J.} and Ruth McPherson and Nu{\~n}ez-Cortes, {Jesus Millan} and Nordestgaard, {B{\o}rge G.} and Hisao Ogawa and Packard, {Chris J.} and Jorge Plutzky and Ponte-Negretti, {Carlos I.} and Aruna Pradhan and Ray, {Kausik K.} and Zeljko Reiner and Ridker, {Paul M.} and Massimiliano Ruscica and Shaukat Sadikot and Hitoshi Shimano and Piyamitr Sritara and Stock, {Jane K.} and Su, {Ta Chen} and Susekov, {Andrey V.} and Andr{\'e} Tartar and Taskinen, {Marja Riitta} and Alexander Tenenbaum and Tokg{\"o}zoǧlu, {Lale S.} and Brian Tomlinson and Anne Tybj{\ae}rg-Hansen and Paul Valensi and Michal Vrabl{\'i}k and Walter Wahli and Watts, {Gerald F.} and Shizuya Yamashita and Koutaro Yokote and Alberto Zambon and Peter Libby",
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month = "6",
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Fruchart, JC, Santos, RD, Aguilar-Salinas, C, Aikawa, M, Al Rasadi, K, Amarenco, P, Barter, PJ, Ceska, R, Corsini, A, Després, JP, Duriez, P, Eckel, RH, Ezhov, MV, Farnier, M, Ginsberg, HN, Hermans, MP, Ishibashi, S, Karpe, F, Kodama, T, Koenig, W, Krempf, M, Lim, S, Lorenzatti, AJ, McPherson, R, Nuñez-Cortes, JM, Nordestgaard, BG, Ogawa, H, Packard, CJ, Plutzky, J, Ponte-Negretti, CI, Pradhan, A, Ray, KK, Reiner, Z, Ridker, PM, Ruscica, M, Sadikot, S, Shimano, H, Sritara, P, Stock, JK, Su, TC, Susekov, AV, Tartar, A, Taskinen, MR, Tenenbaum, A, Tokgözoǧlu, LS, Tomlinson, B, Tybjærg-Hansen, A, Valensi, P, Vrablík, M, Wahli, W, Watts, GF, Yamashita, S, Yokote, K, Zambon, A & Libby, P 2019, 'The selective peroxisome proliferator-activated receptor alpha modulator (SPPARMα) paradigm: Conceptual framework and therapeutic potential', Cardiovascular Diabetology, vol. 18, no. 1, 71. https://doi.org/10.1186/s12933-019-0864-7

The selective peroxisome proliferator-activated receptor alpha modulator (SPPARMα) paradigm : Conceptual framework and therapeutic potential. / Fruchart, Jean Charles; Santos, Raul D.; Aguilar-Salinas, Carlos; Aikawa, Masanori; Al Rasadi, Khalid; Amarenco, Pierre; Barter, Philip J.; Ceska, Richard; Corsini, Alberto; Després, Jean Pierre; Duriez, Patrick; Eckel, Robert H.; Ezhov, Marat V.; Farnier, Michel; Ginsberg, Henry N.; Hermans, Michel P.; Ishibashi, Shun; Karpe, Fredrik; Kodama, Tatsuhiko; Koenig, Wolfgang; Krempf, Michel; Lim, Soo; Lorenzatti, Alberto J.; McPherson, Ruth; Nuñez-Cortes, Jesus Millan; Nordestgaard, Børge G.; Ogawa, Hisao; Packard, Chris J.; Plutzky, Jorge; Ponte-Negretti, Carlos I.; Pradhan, Aruna; Ray, Kausik K.; Reiner, Zeljko; Ridker, Paul M.; Ruscica, Massimiliano; Sadikot, Shaukat; Shimano, Hitoshi; Sritara, Piyamitr; Stock, Jane K.; Su, Ta Chen; Susekov, Andrey V.; Tartar, André; Taskinen, Marja Riitta; Tenenbaum, Alexander; Tokgözoǧlu, Lale S.; Tomlinson, Brian; Tybjærg-Hansen, Anne; Valensi, Paul; Vrablík, Michal; Wahli, Walter; Watts, Gerald F.; Yamashita, Shizuya; Yokote, Koutaro; Zambon, Alberto; Libby, Peter.

In: Cardiovascular Diabetology, Vol. 18, No. 1, 71, 04.06.2019.

Research output: Contribution to journalReview articleResearchpeer-review

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 - PROMINENT

KW - Pemafibrate (K-877)

KW - Remnant cholesterol

KW - Residual cardiovascular risk

KW - SPPARMalpha

KW - Selective peroxisome proliferator-activated receptor alpha modulator

KW - Triglycerides

KW - Visceral obesity

UR - http://www.scopus.com/inward/record.url?scp=85066822428&partnerID=8YFLogxK

U2 - 10.1186/s12933-019-0864-7

DO - 10.1186/s12933-019-0864-7

M3 - Review article

VL - 18

JO - Cardiovascular Diabetology

JF - Cardiovascular Diabetology

SN - 1475-2840

IS - 1

M1 - 71

ER -