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; Ichiro Sakuma; Shinya Hiramitsu; Mizuho Okada; Shinichiro Ueda; Masaru Sakurai

doi:10.3389/fcvm.2023.1094100

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)

Front Cardiovasc Med. 2023 Jan 25:10:1094100. doi: 10.3389/fcvm.2023.1094100. eCollection 2023.

Authors

Yasutaka Takeda¹, Ichiro Sakuma², Shinya Hiramitsu³, Mizuho Okada⁴, Shinichiro Ueda⁵, Masaru Sakurai⁶

Affiliations

¹ Division of Metabolism and Biosystemic Science, Gastroenterology, and Hematology/Oncology, Department of Medicine, Asahikawa Medical University, Asahikawa, Japan.
² Caress Sapporo Hokko Memorial Clinic, Sapporo, Japan.
³ Hiramitsu Heart Clinic, Nagoya, Japan.
⁴ Keiyukai Yoshida Hospital, Asahikawa, Japan.
⁵ Department of Clinical Pharmacology and Therapeutics, University of the Ryukyus, Nishihara, Japan.
⁶ Department of Social and Environmental Medicine, Kanazawa Medical University, Uchinada, Japan.

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.

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.