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

• Published in: Cardiovascular diabetology Vol. 18; no. 1; p. 71
• Main Authors: 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, 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
• Format: Journal Article
• Language: English
• Published: England BioMed Central 04-06-2019
• Subjects: Animals; Benzoxazoles - adverse effects; Benzoxazoles - therapeutic use; Biomarkers - blood; Butyrates - adverse effects; Butyrates - therapeutic use; Cardiovascular Diseases - blood; Cardiovascular Diseases - diagnosis; Cardiovascular Diseases - prevention & control; Consensus; Dyslipidemias - blood; Dyslipidemias - diagnosis; Dyslipidemias - drug therapy; Humans; Hypolipidemic Agents - adverse effects; Hypolipidemic Agents - therapeutic use; Lipids - blood; Molecular Targeted Therapy; Patient Safety; PPAR alpha - agonists; PPAR alpha - metabolism; Review; Risk Assessment; Risk Factors; Signal Transduction; Treatment Outcome; Atherogenic dyslipidemia; SPPARMalpha; Selective peroxisome proliferator-activated receptor alpha modulator; Residual cardiovascular risk; Inflammation; Pemafibrate (K-877); Triglycerides; Diabetes; PROMINENT; Remnant cholesterol; Visceral obesity
• ISSN: 1475-2840; 1475-2840
• DOI: 10.1186/s12933-019-0864-7

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.