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Atherosclerosis. 2017 Jun;261:144-152. doi: 10.1016/j.atherosclerosis.2017.03.032. Epub 2017 Mar 24.

Efficacy and safety of K-877, a novel selective peroxisome proliferator-activated receptor α modulator (SPPARMα), in combination with statin treatment: Two randomised, double-blind, placebo-controlled clinical trials in patients with dyslipidaemia.

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National Center for Geriatrics and Gerontology, Obu, Aichi, Japan. Electronic address:
Department of Community Medicine and Department of Cardiovascular Medicine, Osaka University Graduate School of Medicine, Suita, Osaka, Japan; Rinku General Medical Center, Izumisano, Osaka, Japan.
Department of Clinical Cell Biology and Medicine, Chiba University Graduate School of Medicine, Chiba, Chiba, Japan.
Department of Metabolic Medicine, Faculty of Life Sciences, Kumamoto University, Kumamoto, Kumamoto, Japan.
Clinical Data Science Department, Kowa Company, Ltd., Chuo-ku, Tokyo, Japan.
Division of Endocrinology and Metabolism, Department of Medicine, Jichi Medical University, Shimotsuke, Tochigi, Japan.



Substantial residual cardiovascular risks remain despite intensive statin treatment. Residual risks with high triglyceride and low high-density lipoprotein cholesterol are not the primary targets of statins. K-877 (pemafibrate) demonstrated robust efficacy on triglycerides and high-density lipoprotein cholesterol and a good safety profile as a monotherapy. The aim of these studies was to evaluate the efficacy and safety of K-877 add-on therapy to treat residual hypertriglyceridaemia during statin treatment.


The objectives were investigated in two, multicentre, randomised, double-blind, placebo-controlled, parallel group comparison clinical trials: (A) K-877 0.1, 0.2, and 0.4 mg/day in combination with pitavastatin for 12 weeks in 188 patients, (B) K-877 0.2 (fixed dose) and 0.2 (0.4) (conditional up-titration) mg/day in combination with any statin for 24 weeks in 423 patients.


In both studies, we found a robust reduction in fasting triglyceride levels by approximately 50% in all combination therapy groups, which was significant compared to the statin-monotherapy (placebo) groups (p < 0.001). High-performance liquid chromatography analysis for lipoprotein subfractions revealed that atherogenic lipoprotein profiles were ameliorated by K-877 add-on therapy, i.e. small low-density lipoproteins decreased whereas larger ones increased, and larger high-density lipoproteins decreased whereas smaller ones increased. The incidence rates of adverse events and adverse drug reactions in K-877 combination therapy groups were comparable to those in statin-monotherapy groups without any noteworthy event in both studies.


These results strongly support the favourable benefit-to-risk ratio of K-877 add-on therapy in combination with statin treatment.


Combination therapy; Dyslipidaemia; K-877; Pemafibrate; SPPARMα; Statin; Triglyceride

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