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 journalReview article

33 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 languageEnglish
Article number71
JournalCardiovascular Diabetology
Volume18
Issue number1
DOIs
Publication statusPublished - Jun 4 2019
Externally publishedYes

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

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