The selective peroxisome proliferator-activated receptor alpha modulator (SPPARMα) paradigm: conceptual framework and therapeutic potential : A consensus statement from the International Atherosclerosis Society (IAS) and the Residual Risk Reduction Initiative (R3i) Foundation.

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.

• Authors: 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, Željko 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 Tokgözoğlu, Brian Tomlinson, Anne Tybjærg-Hansen, Paul Valensi, Michal Vrablík, Walter Wahli, Gerald F Watts, Shizuya Yamashita, Koutaro Yokote, Alberto Zambon, Peter Libby
• Journal: Cardiovascular diabetology (Cardiovasc Diabetol) Vol. 18 Issue 1 Pg. 71 (06 04 2019) ISSN: 1475-2840 [Electronic] England
• PMID: 31164165 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Review)

Chemical References

• (R)-2-(3-((benzoxazol-2-yl-d4 (3-(4-methoxyphenoxy-d7)propyl)amino)methyl)phenoxy) butanoic acid
• Benzoxazoles
• Biomarkers
• Butyrates
• Hypolipidemic Agents
• Lipids
• PPAR alpha
• PPARA protein, human

Topics

• Animals
• Benzoxazoles (adverse effects, therapeutic use)
• Biomarkers (blood)
• Butyrates (adverse effects, therapeutic use)
• Cardiovascular Diseases (blood, diagnosis, prevention & control)
• Consensus
• Dyslipidemias (blood, diagnosis, drug therapy)
• Humans
• Hypolipidemic Agents (adverse effects, therapeutic use)
• Lipids (blood)
• Molecular Targeted Therapy
• PPAR alpha (agonists, metabolism)
• Patient Safety
• Risk Assessment
• Risk Factors
• Signal Transduction
• Treatment Outcome