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

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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 Millan | Nordestgaard, Børge G. | Ogawa, Hisao | Packard, Chris J. | Plutzky, Jorge | Ponte-Negretti, Carlos I. | Pradhan, Aruna | Ray, Kausik K. | Reiner, Zeljko | 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 | Vrablik, Michal | Wahli, Walter | Watts, Gerald F. | Yamashita, Shizuya | Yokote, Koutaro | Zambon, Alberto | Libby, Peter

Edité par CCSD ; BioMed Central -

International audience. 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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