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; 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

doi:10.1186/s12933-019-0864-7

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 KoenigMichel 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

^*Corresponding author for this work

Research output: Contribution to journal › Review article › peer-review

99 Citations (Scopus)

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 language	English
Article number	71
Journal	Cardiovascular Diabetology
Volume	18
Issue number	1
DOIs	https://doi.org/10.1186/s12933-019-0864-7
Publication status	Published - Jun 4 2019
Externally published	Yes

Keywords

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

ASJC Scopus subject areas

Internal Medicine
Endocrinology, Diabetes and Metabolism
Cardiology and Cardiovascular Medicine

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

Access to Document

10.1186/s12933-019-0864-7

Cite this

Fruchart, J. C., Santos, R. D., Aguilar-Salinas, C., Aikawa, M., Al Rasadi, K., Amarenco, P., Barter, P. J., Ceska, R., Corsini, A., Després, J. P., Duriez, P., Eckel, R. H., Ezhov, M. V., Farnier, M., Ginsberg, H. N., Hermans, M. P., Ishibashi, S., Karpe, F., Kodama, T., ... Libby, P. (2019). The selective peroxisome proliferator-activated receptor alpha modulator (SPPARMα) paradigm: Conceptual framework and therapeutic potential. Cardiovascular Diabetology, 18(1), Article 71. https://doi.org/10.1186/s12933-019-0864-7

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

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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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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.

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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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The selective peroxisome proliferator-activated receptor alpha modulator (SPPARMα) paradigm: Conceptual framework and therapeutic potential

Abstract

Keywords

ASJC Scopus subject areas

UN SDGs

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