Articles

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 M.; Nordestgaard, Børge G.; Ogawa, Hisao; Packard, Chris J.; Plutzky, Jorge; Ponte-Negretti, Carlos I.; Pradhan, Aruna; Ray, Kausik K.; Reiner, Željko; 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; Tokgözoğlu, 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 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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Also Published In

Title
Cardiovascular Diabetology
DOI
https://doi.org/10.1186/s12933-019-0864-7

More About This Work

Published Here
September 22, 2023

Notes

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