Shizuya Yamashita1, Hidenori Arai2, Koutaro Yokote3, Eiichi Araki4, Hideki Suganami5, Shun Ishibashi6. 1. Department of Community Medicine and Department of Cardiovascular Medicine, Osaka University Graduate School of Medicine, Osaka, Japan; Rinku General Medical Center, Osaka, Japan. Electronic address: shizu@imed2.med.osaka-u.ac.jp. 2. National Center for Geriatrics and Gerontology, Aichi, Japan. 3. Department of Clinical Cell Biology and Medicine, Chiba University Graduate School of Medicine, Chiba, Japan. 4. Department of Metabolic Medicine, Faculty of Life Sciences, Kumamoto University, Kumamoto, Japan. 5. Clinical Data Science Department, Kowa Company, Ltd., Chuo-ku, Tokyo, Japan. 6. Division of Endocrinology and Metabolism, Department of Medicine, Jichi Medical University, Tochigi, Japan.
Abstract
BACKGROUND: Cardiovascular risk is negatively correlated with cholesterol efflux capacity (CEC) from macrophages to high-density lipoproteins (HDLs) and positively correlated with fasting and nonfasting triglyceride-rich lipoproteins (TRLs). Pemafibrate, a novel selective peroxisome proliferator-activated receptor α modulator, robustly decreases the fasting TRL level, increases the HDL cholesterol (HDL-C) level, and improves the atherogenic lipoprotein subclass profile, with an adverse event rate comparable to that of placebo treatment in previous clinical studies. OBJECTIVE: This study aimed to investigate the effects of pemafibrate on CEC and postprandial hyperlipidemia. METHODS: Using a single-center, double-blind, randomized, two-by-two crossover design, 33 patients were assigned to receive either 0.4 mg/d pemafibrate (twice daily) or placebo first. The assigned study drug was administered for 4 weeks. Subsequently, the alternate study drug was administered for another 4 weeks. CEC was measured using HDLs obtained from fasting blood samples. A meal tolerance test was performed to examine the postprandial lipid levels at weeks 0, 4, and 8. RESULTS:CEC, HDL-C, and apolipoprotein A-I levels increased after pemafibrate treatment compared with placebo administration. Moreover, the percent change in CEC was correlated with that of HDL-C and apolipoprotein A-I levels. TRL levels markedly decreased after pemafibrate treatment in both fasting and nonfasting states. CONCLUSIONS: These findings suggest that pemafibrate enhances reverse cholesterol transport and may retard the progression and even promote the regression of atherosclerosis by comprehensively ameliorating the atherogenic lipid profile.
RCT Entities:
BACKGROUND: Cardiovascular risk is negatively correlated with cholesterol efflux capacity (CEC) from macrophages to high-density lipoproteins (HDLs) and positively correlated with fasting and nonfasting triglyceride-rich lipoproteins (TRLs). Pemafibrate, a novel selective peroxisome proliferator-activated receptor α modulator, robustly decreases the fasting TRL level, increases the HDL cholesterol (HDL-C) level, and improves the atherogenic lipoprotein subclass profile, with an adverse event rate comparable to that of placebo treatment in previous clinical studies. OBJECTIVE: This study aimed to investigate the effects of pemafibrate on CEC and postprandial hyperlipidemia. METHODS: Using a single-center, double-blind, randomized, two-by-two crossover design, 33 patients were assigned to receive either 0.4 mg/d pemafibrate (twice daily) or placebo first. The assigned study drug was administered for 4 weeks. Subsequently, the alternate study drug was administered for another 4 weeks. CEC was measured using HDLs obtained from fasting blood samples. A meal tolerance test was performed to examine the postprandial lipid levels at weeks 0, 4, and 8. RESULTS: CEC, HDL-C, and apolipoprotein A-I levels increased after pemafibrate treatment compared with placebo administration. Moreover, the percent change in CEC was correlated with that of HDL-C and apolipoprotein A-I levels. TRL levels markedly decreased after pemafibrate treatment in both fasting and nonfasting states. CONCLUSIONS: These findings suggest that pemafibrate enhances reverse cholesterol transport and may retard the progression and even promote the regression of atherosclerosis by comprehensively ameliorating the atherogenic lipid profile.
Authors: Jean-Charles Fruchart; Raul D Santos; Carlos Aguilar-Salinas; Masanori Aikawa; Khalid Al Rasadi; Pierre Amarenco; Philip J Barter; Richard Ceska; Alberto Corsini; Jean-Pierre Després; Patrick Duriez; Robert H Eckel; Marat V Ezhov; Michel Farnier; Henry N Ginsberg; Michel P Hermans; Shun Ishibashi; Fredrik Karpe; Tatsuhiko Kodama; Wolfgang Koenig; Michel Krempf; Soo Lim; Alberto J Lorenzatti; Ruth McPherson; Jesus Millan Nuñez-Cortes; Børge G Nordestgaard; Hisao Ogawa; Chris J Packard; Jorge Plutzky; Carlos I Ponte-Negretti; Aruna Pradhan; Kausik K Ray; Željko Reiner; Paul M Ridker; Massimiliano Ruscica; Shaukat Sadikot; Hitoshi Shimano; Piyamitr Sritara; Jane K Stock; Ta-Chen Su; Andrey V Susekov; André Tartar; Marja-Riitta Taskinen; Alexander Tenenbaum; Lale S Tokgözoğlu; Brian Tomlinson; Anne Tybjærg-Hansen; Paul Valensi; Michal Vrablík; Walter Wahli; Gerald F Watts; Shizuya Yamashita; Koutaro Yokote; Alberto Zambon; Peter Libby Journal: Cardiovasc Diabetol Date: 2019-06-04 Impact factor: 9.951