Crossover Trial of Pemafibrate and Omega-3-Acid Ethyl Esters for Hypertriglyceridemia in Patients with Cardiovascular Disease

Scritto il 12/02/2026
da Akira Sezai

JMA J. 2026 Jan 15;9(1):271-282. doi: 10.31662/jmaj.2025-0177. Epub 2025 Dec 5.

ABSTRACT

INTRODUCTION: Statins can treat dyslipidemia, but even if low-density lipoprotein decreases to target levels, high triglyceride (TG) levels may represent a residual risk. Therefore, we performed a crossover study comparing pemafibrate and omega-3-acid ethyl esters docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA) in patients with untreated hypertriglyceridemia.

METHODS: Patients were randomized by the envelope method to pemafibrate or DHA+EPA for 6 months and then switched to the other medication for 6 months. The primary endpoint was TG level, and secondary endpoints were lipid markers, fatty acid 4-fractionation, kidney and liver markers, and the Fibrosis-4 index.

RESULTS: In the 36 analyzed patients, pemafibrate showed a significantly greater decrease in TG (p < 0.001) and remnant-like particles cholesterol (p = 0.001) and a significantly greater increase in high-density lipoprotein (p < 0.001), but DHA+EPA showed a significantly greater improvement in fatty acid 4-fractionation (p < 0.001).

CONCLUSIONS: When combined with a statin, pemafibrate appears to have a stronger effect in lowering TG and remnant-like particles cholesterol but DHA+EPA appears to be more effective in terms of fatty acids. Pemafibrate may be an effective first choice for hypertriglyceridemia, and add-on DHA+EPA may be beneficial when pemafibrate is not sufficiently effective. Findings need to be confirmed in larger studies.

PMID:41676815 | PMC:PMC12889709 | DOI:10.31662/jmaj.2025-0177