Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2023 Jan 25:10:1094100.
doi: 10.3389/fcvm.2023.1094100. eCollection 2023.

The effects of pemafibrate and omega-3 fatty acid ethyl on apoB-48 in dyslipidemic patients treated with statin: A prospective, multicenter, open-label, randomized, parallel group trial in Japan (PROUD48 study)

Yasutaka Takeda  1 , Ichiro Sakuma  2 , Shinya Hiramitsu  3 , Mizuho Okada  4 , Shinichiro Ueda  5 , Masaru Sakurai  6
Affiliations

The effects of pemafibrate and omega-3 fatty acid ethyl on apoB-48 in dyslipidemic patients treated with statin: A prospective, multicenter, open-label, randomized, parallel group trial in Japan (PROUD48 study)

Yasutaka Takeda et al. Front Cardiovasc Med. .

Erratum in

Abstract

Background: We compared the lowering effects of pemafibrate and omega-3 fatty acid ethyl on fasting apolipoprotein (apo) B-48 (apoB-48), a marker that reflects postprandial hypertriglyceridemia, which is one of the residual risks for atherosclerotic cardiovascular disease (ASCVD) with statin treatment.

Methods: This prospective, multicenter, open-label, randomized, parallel group trial was conducted at 4 medical institutions between April 2020 and May 2022. A total of 126 ambulatory patients with dyslipidemia receiving statin treatment for more than 4 weeks, aged 20-79 years with fasting triglyceride (TG) levels of ≥177 mg/dl were randomly assigned to 16-week pemafibrate 0.4 mg per day treatment group (PEMA, n = 63) or omega-3 fatty acid ethyl 4 g per day treatment group (OMEGA-3, n = 63). The primary endpoint was the percentage change in fasting apoB-48 from baseline to week 16.

Results: The percentage changes in fasting apoB-48 in PEMA and OMEGA-3 were -50.8% (interquartile range -62.9 to -30.3%) and -17.5% (-38.3 to 15.3%) (P < 0.001), respectively. As the secondary endpoints, the changes in fasting apoB-48 in PEMA and OMEGA-3 were -3.10 μg/ml (-5.63 to -1.87) and -0.90 μg/ml (-2.95 to 0.65) (P < 0.001), respectively. Greater decreases with significant differences in the percentage changes in TG, remnant lipoprotein cholesterol, apoC-III, fasting plasma glucose, alanine aminotransferase, gamma-glutamyl transpeptidase, and alkaline phosphatase were observed in PEMA, compared with OMEGA-3. Greater increases with significant differences in those in high-density lipoprotein (HDL) cholesterol, apoA-I, and apoA-II were observed in PEMA, compared with OMEGA-3. PEMA showed anti-atherosclerotic lipoprotein profiles in gel-permeation high-performance liquid chromatography analyses, compared with OMEGA-3. Although adverse events occurred in 9 of 63 (14.3%) patients in PEMA and 3 of 63 (4.8%) patients in OMEGA-3, no serious adverse events associated with drug were observed in either group.

Conclusions: This is the first randomized trial to compare the lowering effects of pemafibrate and omega-3 fatty acid ethyl on fasting apoB-48. We concluded that pemafibrate was superior to omega-3 fatty acid ethyl in lowering effect of fasting apoB-48. Pemafibrate is expected to reduce the residual risk for ASCVD with statin treatment.

Clinical trial registration: https://rctportal.niph.go.jp/en, identifier jRCTs071200011.

Keywords: apolipoprotein B-48; atherosclerotic cardiovascular disease; hypertriglyceridemia; pemafibrate; polyunsaturated fatty acids (PUFAs); residual risk.

PubMed Disclaimer

Conflict of interest statement

IS received an honorarium for a lecture from GlaxoSmithKline and research funding from Kowa. SH has received honoraria for lectures from Bayer Yakuhin, Daiichi Sankyo, Kowa, Mitsubishi Tanabe Pharma, MSD, Novartis Pharma, Otsuka Pharmaceutical, and Takeda Pharmaceutical. SU has received honoraria for lectures from Daiichi Sankyo, Kowa, and Taiho Pharmaceutical and grants from Bayer Yakuhin, Bristol-Myers Squibb, and Kowa. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

FIGURE 1
FIGURE 1
Flow chart of participant recruitment.
See this image and copyright information in PMC

Similar articles

See all similar articles

Cited by

References

    1. Baigent C, Keech A, Kearney P, Blackwell L, Buck G, Pollicino C, et al. Efficacy and safety of cholesterol-lowering treatment: prospective meta-analysis of data from 90,056 participants in 14 randomised trials of statins. Lancet. (2005) 366:1267–78. 10.1016/S0140-6736(05)67394-1 - DOI - PubMed
    1. Cholesterol Treatment Trialists’ [CTT] Collaboration Baigent C, Blackwell L, Emberson J, Holland L, Reith C, et al. Efficacy and safety of more intensive lowering of LDL cholesterol: a meta-analysis of data from 170,000 participants in 26 randomised trials. Lancet. (2010) 376:1670–81. 10.1016/S0140-6736(10)61350-5 - DOI - PMC - PubMed
    1. Cholesterol Treatment Trialists’ [CTT] Collaborators Mihaylova B, Emberson J, Blackwell L, Keech A, Simes J, et al. The effects of lowering LDL cholesterol with statin therapy in people at low risk of vascular disease: meta-analysis of individual data from 27 randomised trials. Lancet. (2012) 380:581–90. 10.1016/S0140-6736(12)60367-5 - DOI - PMC - PubMed
    1. Cholesterol Treatment Trialists’ [CTT] Collaboration Fulcher J, O’Connell R, Voysey M, Emberson J, Blackwell L, et al. Efficacy and safety of LDL-lowering therapy among men and women: meta-analysis of individual data from 174,000 participants in 27 randomised trials. Lancet. (2015) 385:1397–405. 10.1016/S0140-6736(14)61368-4 - DOI - PubMed
    1. Bainton D, Miller N, Bolton C, Yarnell J, Sweetnam P, Baker I, et al. Plasma triglyceride and high density lipoprotein cholesterol as predictors of ischaemic heart disease in British men. the caerphilly and speedwell collaborative heart disease studies. Br Heart J. (1992) 68:60–6. 10.1136/hrt.68.7.60 - DOI - PMC - PubMed

Grants and funding

This trial was funded by Kowa, Tokyo, Japan, including journal article processing charges. The design of the study, collection, analysis and interpretation of all data and drafting of the manuscript were conducted solely by the authors.