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.
| Original language | English |
|---|---|
| Article number | 71 |
| Journal | Cardiovascular Diabetology |
| Volume | 18 |
| Issue number | 1 |
| DOIs | |
| Publication status | Published - Jun 4 2019 |
| Externally published | Yes |
Keywords
- Atherogenic dyslipidemia
- Diabetes
- Inflammation
- Pemafibrate (K-877)
- PROMINENT
- Remnant cholesterol
- Residual cardiovascular risk
- Selective peroxisome proliferator-activated receptor alpha modulator
- SPPARMalpha
- Triglycerides
- Visceral obesity
ASJC Scopus subject areas
- Internal Medicine
- Endocrinology, Diabetes and Metabolism
- Cardiology and Cardiovascular Medicine
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The selective peroxisome proliferator-activated receptor alpha modulator (SPPARMα) paradigm : Conceptual framework and therapeutic potential. / 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; Tokgözoǧlu, Lale S.; Tomlinson, Brian; Tybjærg-Hansen, Anne; Valensi, Paul; Vrablík, Michal; Wahli, Walter; Watts, Gerald F.; Yamashita, Shizuya; Yokote, Koutaro; Zambon, Alberto; Libby, Peter.
In: Cardiovascular Diabetology, Vol. 18, No. 1, 71, 04.06.2019.Research output: Contribution to journal › Review article › peer-review
}
TY - JOUR
T1 - The selective peroxisome proliferator-activated receptor alpha modulator (SPPARMα) paradigm
T2 - Conceptual framework and therapeutic potential
AU - Fruchart, Jean Charles
AU - Santos, Raul D.
AU - Aguilar-Salinas, Carlos
AU - Aikawa, Masanori
AU - Al Rasadi, Khalid
AU - Amarenco, Pierre
AU - Barter, Philip J.
AU - Ceska, Richard
AU - Corsini, Alberto
AU - Després, Jean Pierre
AU - Duriez, Patrick
AU - Eckel, Robert H.
AU - Ezhov, Marat V.
AU - Farnier, Michel
AU - Ginsberg, Henry N.
AU - Hermans, Michel P.
AU - Ishibashi, Shun
AU - Karpe, Fredrik
AU - Kodama, Tatsuhiko
AU - Koenig, Wolfgang
AU - Krempf, Michel
AU - Lim, Soo
AU - Lorenzatti, Alberto J.
AU - McPherson, Ruth
AU - Nuñez-Cortes, Jesus Millan
AU - Nordestgaard, Børge G.
AU - Ogawa, Hisao
AU - Packard, Chris J.
AU - Plutzky, Jorge
AU - Ponte-Negretti, Carlos I.
AU - Pradhan, Aruna
AU - Ray, Kausik K.
AU - Reiner, Zeljko
AU - Ridker, Paul M.
AU - Ruscica, Massimiliano
AU - Sadikot, Shaukat
AU - Shimano, Hitoshi
AU - Sritara, Piyamitr
AU - Stock, Jane K.
AU - Su, Ta Chen
AU - Susekov, Andrey V.
AU - Tartar, André
AU - Taskinen, Marja Riitta
AU - Tenenbaum, Alexander
AU - Tokgözoǧlu, Lale S.
AU - Tomlinson, Brian
AU - Tybjærg-Hansen, Anne
AU - Valensi, Paul
AU - Vrablík, Michal
AU - Wahli, Walter
AU - Watts, Gerald F.
AU - Yamashita, Shizuya
AU - Yokote, Koutaro
AU - Zambon, Alberto
AU - Libby, Peter
N1 - Funding Information: The following authors report disclosures outside the submitted work. These relate to grants and personal fees (honoraria for consultancy, lectures and/ or advisory bureaux). J‑CFruchart reports personal fees from Kowa Com‑ pany. RD Santos reports personal fees from Amgen, AstraZeneca, Merck, Akcea, Sanofi/Regeneron, Biolab, Esperion, Kowa, and Novo‑Nordisk. M Aikawa reports grants from Kowa Company, Ltd., Pfizer, Inc., and Sanofi, Inc. P Amarenco reports personal fees from Kowa, grants and personal fees from Pfizer, Sanofi, Bristol Myers Squibb, Boston Scientific and AstraZeneca, grants from Merck, and personal fees from Amgen, GSK, Fibrogen and Shin Poong. PJ Barter reports personal fees from Amgen, Sanofi, and Pfizer. A Corsini reports personal fees from AstraZeneca, Amgen, Sanofi, Recordati, Novartis, MSD, Mediolanum, DOC, Mylan and Pfizer. RH Eckel reports grants from NINDS, NIA, NHLBI, Ionis Pharmaceutical, Uniqure Biopharma, CTSA Pilot Project, Endece, LLC, personal fees from Cardiometabolic Health Congress, Prime, Medtel‑ ligence, Medscape, Medical Education Resources, Vox Media, Sanofi/Regen‑ eron, Merck, Novo Nordisk, and Kowa. M Farnier reports grants, consulting fees and/or honoraria for delivering lectures for Abbott, Akcea/Ionis, Amarin, Amgen, AstraZeneca, Daiichi‑Sankyo, Eli Lilly, Kowa, Merck and Co, Mylan, Pfizer, Sanofi/Regeneron and Servier. HN Ginsberg reports and consults for Kowa, a pharmaceutical company that has a SPPARMalpha in clinical trials for the treatment of dyslipidemia and prevention of cardiovascular disease. MP Hermans reports personal fees from Amgen, AstraZeneca, MSD, Mylan, Sanofi‑ Aventis, Teva, and Tilman. S Ishibashi reports personal fees from Kowa, grants from Astellas Pharma, Boehringer Ingelheim, Daiichi Sankyo, Ono Pnharma, Shionogi, and Teijin Pharma. T Kodama is the recipient of a research grant from Kowa Company. W Koenig reports personal fees from AstraZeneca, Novartis, Pfizer, The Medicines Company, GSK, DalCor, Sanofi, Berlin‑Chemie, Kowa, Amgen, grants and non‑financial support from Roche Diagnostics, Beckmann, Singulex, and Abbott. M Krempf reports personal fees from Amgen, Sanofi Regeneron, MSD, Novartis, Abbott, Servier, AstraZeneca and grants from Pfizer. P Libby reports a research grant from Novartis and honoraria as a scientific advisory board member for Dalcor Pharmaceuticals. He also provides unpaid consultancy for Amgen, AstraZeneca, Ionis Pharmaceuticals, Kowa Pharma‑ ceuticals, Pfizer, Sanofi‑Regeneron, XBiotech Inc., Corvidia Therapeutics, IFM Therapeutics, Olatec Therapeutics, Medimmune and Esperion Therapeutics. AJ Lorenzatti reports grants and personal fees from Amgen, Kowa, personal fees from Sanofi, Pfizer, and grants from Resverlogix. BG Nordestgaard reports per‑ sonal fees from AstraZeneca, Sanofi, Regeneron, Ionis, Akcea, Amgen, Kowa, Denka Seiken, Amarin and Kowa. CJ Packard reports grants from MSD, and personal fees from Sanofi/Regeneron, Amgen, and Daiichi‑Sankyo. A Pradhan reports grants from Kowa Research Institute. KK Ray reports grants from Sanofi, Regeneron, Pfizer, Amgen, MSD, and honoraria for lectures/speaker’s bureau or consultancy from Sanofi, Amgen, Regeneron, Lilly, Medicines Company, Astra Zeneca, Pfizer, Kowa, Algorithm, IONIS, Esperion, Novo Nordisk, Takeda, Boehringer Ingelheim, Resverlogix, and Abbvie. Z Reiner reports personal fees from Sanofi Aventis and Akcea. PM Ridker reports grants from Kowa, Inc, Novartis, and Pfizer. H Shimano reports grants and personal fees from Kowa Company Ltd., Kowa Pharmaceutical Co. Ltd., MSD K.K., DAIICHI SANKYO Co., Ltd., Takeda Pharmaceutical Co.,Ltd., Astellas Pharma Inc., AstraZeneca K.K., ONO PHARMACEUTICAL CO., LTD., Nippon Boehringer lngelheim Co., Ltd., Eli Lilly Japan, Mitsubishi Tanabe Pharma Corporation, Sanofi K.K., MOCHIDA PHARMACEUTICAL CO., LTD., Novartis Pharma K.K., Bayer Yakuhin, Ltd., SHIONOGI & CO., LTD., and Taisho Toyama Pharmaceutical Co., Ltd. A Susekov reports personal fees from AstraZeneca, Pfizer, Sanofi, KRKA, Teva and Kowa. MR Taskinen reports grants and personal fees from Amgen, NovoNordisk, and personal fees from Sanofi and Akcea. LS Tokgözoğlu reports personal fees from Abbott, Merck, Amgen, Astra, Novartis, Daiichi Sankyo, Pfizer, Actelion, Servier, Sanofi, Menarini, Mylan, Recordati and Novonordisk. B Tomlinson reports grants from Amgen, Merck Sharp and Dohme, Pfizer, Roche, and personal fees from Amgen, Dr. Reddy’s Laboratories Ltd, Merck Serono and Sanofi. P Valensi reports personal fees from Abbott, AstraZeneca, Merck‑Sharp Dohme, Novo‑Nordisk, and Sanofi‑Aventis. M Vrablík reports personal fees from Abbott, Actavis, AstraZeneca, Amgen, BMS, Genzyme, KRKA, MSD Idea, Novartis, Pfizer and Sanofi‑Regeneron. GF Watts reports support from Kowa for a lecture in Japan; honoraria (for advisory boards and lectures) and research grants from Amgen, Sanofi, and Regeneron; and honoraria (for advisory board) from Gemphire. S Yamashita reports grants and personal fees from Kowa Company, Ltd., Otsuka Pharmaceutical Co., Ltd., Shionogi & Co., Ltd., Bayer Yakuhin, Ltd., MSD K.K., Takeda Pharmaceutical Company, Ltd., Sanwa Kagaku Kenkyusho Co., Ltd., Astellas Pharma Inc., Daiichi‑Sankyo Company, Ltd., Astra Zeneka K.K., Kaken Pharmaceutical Co., Ltd., grants from Nippon Boehringer Ingelheim Co., Ltd., National Institute of Biomedical Innovation, Kyowa Medex Co., Ltd., Mochida Pharmaceutical Company, Ltd., Hayashibara Co., Ltd., Teijin Pharma Limited and Kissei; and personal fees from Ono Pharmaceutical Company, Ltd., Skylight Biotec, Inc., Pfizer, Astellas Amgen, Sanofi, and Aegerion In addition, S Yamashita has a patent PCT/JP2016/074402 (Assisting Method for the Diagno‑ sis of Type III Hyperlipidemia) pending to Fujirebio & Osaka University, a patent PCT/JP2017/038766 (Method for Selecting Subject Needing Treatment for Dyslipidemia and Reagent for Such Selection) pending to Osaka University & Kyowa Medex Co., Ltd., and a patent PCT/JP2017/038715 (Method for Measur‑ ing Oxidized High‑Density Lipoprotein) pending to Osaka University & Kyowa Medex Co., Ltd.. A Zambon reports honoraria for lectures from Abbott, Amgen, Sanofi and Mylan. K Yokote reports grants and personal fees from Kowa Pharmaceutical Co, Astellas, AstraZeneca, MSD, Sanofi, Takeda, Pfizer, Mochida, and personal fees from Kowa Company, Astellas‑Amgen Biopharm, and Bayer. C Aguilar‑Salinas, K Al Rasadi, R Ceska, JP Després, P Duriez, MV Ezhov, F Karpe, S Lim, R McPherson, J Millan Nuñez‑Cortes, H Ogawa, CI Ponte‑Negretti, J Plutzky, M Ruscica, S Sadikot, P Sritara, JK Stock, T‑C Su, A Tartar, A Tenenbaum, A Tybjærg‑Hansen, W Wahli have no competing interests in relation to this manuscript. Publisher Copyright: © 2019 The Author(s).
PY - 2019/6/4
Y1 - 2019/6/4
N2 - 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.
AB - 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.
KW - Atherogenic dyslipidemia
KW - Diabetes
KW - Inflammation
KW - Pemafibrate (K-877)
KW - PROMINENT
KW - Remnant cholesterol
KW - Residual cardiovascular risk
KW - Selective peroxisome proliferator-activated receptor alpha modulator
KW - SPPARMalpha
KW - Triglycerides
KW - Visceral obesity
UR - http://www.scopus.com/inward/record.url?scp=85066822428&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85066822428&partnerID=8YFLogxK
U2 - 10.1186/s12933-019-0864-7
DO - 10.1186/s12933-019-0864-7
M3 - Review article
C2 - 31164165
AN - SCOPUS:85066822428
VL - 18
JO - Cardiovascular Diabetology
JF - Cardiovascular Diabetology
SN - 1475-2840
IS - 1
M1 - 71
ER -