Cited by 125Lipoproteins and Cardiovascular HealthPeroxisome Proliferator-Activated ReceptorsLipid metabolism and disorders

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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Arai, Hidenori, Yamashita, Shizuya, Yokote, Koutaro, Araki, Eiichi, Suganami, Hideki, Ishibashi, Shun·2017·Atherosclerosis

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.

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Crossref · 10.1016/j.atherosclerosis.2017.03.032

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  • Data from Arai 2017, Araki 2018, Araki 2019, Dai 2025, Das 2022, Ginsberg 2022, and Matsuba 2018 showed no significant difference in total adverse events between pemafibrate and placebo, with a risk ratio of 1.02 (95% CI: 0.98, 1.07, p = 0.30) and I2 = 0%.

    “Data from Arai 2017, Araki 2018, Araki 2019, Dai 2025, Das 2022, Ginsberg 2022, and Matsuba 2018 showed an RR of 1.02 (95% CI: 0.98, 1.07, p = 0.30), suggesting no significant difference in total adverse events between pemafibrate and placebo (I2 = 0%) (high certainty).”

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Authors
Arai, H., Yamashita, S., Yokote, K., Araki, E., Suganami, H., & Ishibashi, S.
Affiliations
  • National Center for Geriatrics and Gerontology (JP)
  • Rinku General Medical Center (JP)
  • Chiba University (JP)
  • Kumamoto University (JP)
  • Kowa (Japan) (JP)
  • Jichi Medical University (JP)
Corresponding author
Arai, Hidenori
Venue
Atherosclerosis
Publisher
Elsevier BV
Published
2017-06
Volume
261
Pages
144-152
ISSN
0021-9150 (ISSN-L)
OpenAlex
W2599479486
Cited by
124
References
46
Citations by year
2026: 2 · 2025: 11 · 2024: 11 · 2023: 16 · 2022: 10 · 2021: 13 · 2020: 13 · 2019: 18 · 2018: 16 · 2017: 13 · 2013: 1
FWCI
16.81
Type
journal article
Language
en
Open access
Locations
  • Atherosclerosis (publishedVersion, cc-by-nc-nd)
  • PubMed (publishedVersion)
Funders
  • Kowa Company
  • Astellas Pharma
  • Japan Society for the Promotion of Science (17H02100)
Topics
  • Health Sciences › Medicine › Surgery › Lipoproteins and Cardiovascular Health
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Peroxisome Proliferator-Activated Receptors
  • Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Lipid metabolism and disorders
Keywords
pemafibrate, statin combination therapy, dyslipidemia, triglyceride lowering, HDL cholesterol, atherogenic lipoprotein profile, pitavastatin, adjunctive therapy, drug safety
MeSH terms
Adult, Aged, Hypolipidemic Agents, Benzoxazoles, Butyrates, Double-Blind Method, Drug Therapy, Combination, Female, Humans, Japan, Male, Middle Aged, Quinolines, Time Factors, Triglycerides, Hypertriglyceridemia, Signal Transduction, Biomarkers, Treatment Outcome, Hydroxymethylglutaryl-CoA Reductase Inhibitors, PPAR alpha, Young Adult

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