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

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Cardiovascular Diabetology. 2019 Jun 04;18(1):71

Title: The selective peroxisome proliferator-activated receptor alpha modulator (SPPARMα) paradigm: conceptual framework and therapeutic potential
Author: 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
Abstract: 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.
URI: http://hdl.handle.net/10138/302630
Date: 2019-06-04
Subject: Residual cardiovascular risk
Visceral obesity
Diabetes
Atherogenic dyslipidemia
Triglycerides
Remnant cholesterol
Selective peroxisome proliferator-activated receptor alpha modulator
SPPARMalpha
Pemafibrate (K-877)
Inflammation
PROMINENT
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