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

Jean-Charles Fruchart (1) , Raul D. Santos (2, 3) , Carlos Aguilar-Salinas (4, 5) , Masanori Aikawa (6) , Khalid Al Rasadi (7) , Pierre Amarenco (8) , Philip J. Barter (9) , Richard Ceska (10) , Alberto Corsini (11) , Jean-Pierre Després (12) , Patrick Duriez (13) , Robert H. Eckel (14) , Marat V. Ezhov (15) , Michel Farnier (16) , Henry N. Ginsberg (17) , Michel P. Hermans (18, 19) , Shun Ishibashi (20) , Fredrik Karpe (21, 22) , Tatsuhiko Kodama (23) , Wolfgang Koenig (24, 25, 26) , Michel Krempf (27, 28, 29) , Soo Lim (30, 31) , Alberto J. Lorenzatti (32, 33) , Ruth Mcpherson (34) , Jesus Millan Nuñez-Cortes (35, 36, 37) , Børge G. Nordestgaard (38, 39) , Hisao Ogawa (40) , Chris J. Packard (41) , Jorge Plutzky (42) , Carlos I. Ponte-Negretti (43) , Aruna Pradhan (44, 6) , Kausik K. Ray (45) , Zeljko Reiner (46, 47) , Paul M. Ridker (6, 48, 49) , Massimiliano Ruscica (11) , Shaukat Sadikot (50) , Hitoshi Shimano (51) , Piyamitr Sritara (52) , Jane K. Stock (1) , Ta-Chen Su (53) , Andrey V. Susekov (54) , André Tartar (55) , Marja-Riitta Taskinen (56, 57) , Alexander Tenenbaum (58, 59) , Lale S. Tokgözoğlu (60) , Brian Tomlinson (61) , Anne Tybjærg-Hansen (39, 62, 38) , Paul Valensi (63) , Michal Vrablik (64, 10) , Walter Wahli (65, 66, 67) , Gerald F. Watts (68, 69) , Shizuya Yamashita (70, 71) , Koutaro Yokote (72) , Alberto Zambon (73) , Peter Libby (48, 6)

1 R3i Foundation
2 Hospital Israelita Albert Einstein [São Paulo, Brazil]
3 Lipid Clinic Heart Institute (InCor)
4 Instituto Nacional de Ciencias Médicas y Nutrición “Salvador Zubirán”
5 ITESM - Tecnológico de Monterrey = Monterrey Institute of Technology
6 Brigham and Women's Hospital [Boston]
7 SQU - Sultan Qaboos University
8 Department of Neurology
9 UNSW - University of New South Wales [Sydney]
10 General University Hospital in Prague
11 UNIMI - Università degli Studi di Milano = University of Milan
12 ULaval - Université Laval [Québec]
13 Université de Lille
14 University of Colorado Cancer Center [Aurora, CO, USA]
15 Russian Cardiology Research Center
16 CHU Dijon - Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand
17 Columbia University [New York]
18 Cliniques Universitaires Saint Luc
19 Institut de Recherche Expérimentale et Clinique (IREC)
20 Jichi Medical University [Tochigi-Ken, Japan]
21 University of Oxford
22 The Churchill hospital
23 UTokyo - The University of Tokyo
24 DHM - Deutsches Herzzentrum München
25 DZHK (German Centre for Cardiovascular Research), Partner site Heidelberg/Mannheim, Heidelberg
26 Universität Ulm - Ulm University [Ulm, Allemagne]
27 PhAN - Physiopathologie des Adaptations Nutritionnelles
28 Department of Endocrinology, Metabolic Diseases and Nutrition
29 Centre de recherche en nutrition humaine Ouest
30 SNUBH - Seoul National University Bundang Hospital
31 SNU - Seoul National University [Seoul]
32 Rusculleda Foundation for Research
33 Hospital Córdoba
34 University of Ottawa [Ottawa]
35 Hospital General Universitario "Gregorio Marañón"
36 UCM - Universidad Complutense de Madrid = Complutense University of Madrid [Madrid]
37 Instituto de Investigaciones Sanitarias Gregorio Marañón
38 University Hospital Herlev Gentofte
39 Faculty of Health and Medical Sciences
40 NCCC - OSAKA - National Cerebral and Cardiovascular Center
41 Institute of Cardiovascular and Medical Sciences
42 Brigham and Women’s Hospital [Boston, MA]
43 Hospital El Pino
44 Boston University Medical Center
45 Imperial College London
46 School of Medicine
47 University Hospital Centre Zagreb
48 HMS - Harvard Medical School [Boston]
49 Massachusetts General Hospital
50 Jaslok Hospital & Research Centre
51 Université de Tsukuba = University of Tsukuba
52 Mahidol University [Bangkok]
53 National Taiwan University
54 Faculty of Clinical Pharmacology and Therapeutics
55 Faculté de Pharmacie
56 Clinical Research Institute HUCH
57 Helsingin yliopisto = Helsingfors universitet = University of Helsinki
58 TAU - Tel Aviv University
59 Chaim Sheba Medical Center
60 Hacettepe University = Hacettepe Üniversitesi
61 Chinese University of Hong Kong
62 Copenhagen University Hospitals
63 Hôpital Jean Verdier [AP-HP]
64 UK - Univerzita Karlova [Praha, Česká republika] = Charles University [Prague, Czech Republic]
65 ToxAlim - ToxAlim
66 CIG - Center for Integrative Genomics - Institute of Bioinformatics, Génopode
67 Lee Kong Chian School of Medicine
68 Royal Perth Hospital
69 UWA - The University of Western Australia
70 Medical Center
71 Osaka University
72 Chiba University
73 Department of Medicine (DIMED)

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.

Mots clés: residual cardiovascular risk; visceral obesity; diabetes; atherogenic dyslipidemia; triglycerides; remnant cholesterol; selective peroxisome proliferator-activated receptor alpha modulator

Mots clés: pemafibrate (K-877); inflammation

Domaines: Médecine humaine et pathologie

Jean-Charles Fruchart, Raul D. Santos, Carlos Aguilar-Salinas, Masanori Aikawa, Khalid Al Rasadi, et al.. The selective peroxisome proliferator-activated receptor alpha modulator (SPPARMα) paradigm: conceptual framework and therapeutic potential. Cardiovascular Diabetology, 2019, 18 (1), 20 p. ⟨10.1186/s12933-019-0864-7⟩. ⟨hal-02626545⟩