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

• Main Authors: Fruchart, Jean-Charles, Santos, Raul D., Aguilar-Salinas, Carlos, Aikawa, Masanori, Kodama, Tatsuhiko, Rasadi, Khalid Al, 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, 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, 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
• Other Authors: Lee Kong Chian School of Medicine (LKCMedicine)
• Format: Article
• Language: English
• Published: 2019
• Subjects: Residual Cardiovascular Risk; Visceral Obesity; Science::Medicine
• Online Access: https://hdl.handle.net/10356/87826; http://hdl.handle.net/10220/49307
• Institution: Nanyang Technological University

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.