Format

Send to

Choose Destination
See comment in PubMed Commons below
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.

Author information

1
National Center for Geriatrics and Gerontology, Obu, Aichi, Japan. Electronic address: harai@ncgg.go.jp.
2
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.
3
Department of Clinical Cell Biology and Medicine, Chiba University Graduate School of Medicine, Chiba, Chiba, Japan.
4
Department of Metabolic Medicine, Faculty of Life Sciences, Kumamoto University, Kumamoto, 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, Shimotsuke, Tochigi, Japan.

Abstract

BACKGROUND AND AIMS:

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.

METHODS:

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.

RESULTS:

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.

CONCLUSIONS:

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

KEYWORDS:

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

Free full text
PubMed Commons home

PubMed Commons

0 comments
How to join PubMed Commons

    Supplemental Content

    Full text links

    Icon for Elsevier Science
    Loading ...
    Support Center