Managing hypertriglyceridemia for cardiovascular disease prevention: Lessons from the PROMINENT trial

Shizuya Yamashita; Tsutomu Hirano; Hitoshi Shimano; Kazuhisa Tsukamoto; Masayuki Yoshida; Hiroshi Yoshida

doi:10.1111/eci.14227

Managing hypertriglyceridemia for cardiovascular disease prevention: Lessons from the PROMINENT trial

Eur J Clin Invest. 2024 Apr 25:e14227. doi: 10.1111/eci.14227. Online ahead of print.

Authors

Shizuya Yamashita¹, Tsutomu Hirano², Hitoshi Shimano³, Kazuhisa Tsukamoto⁴, Masayuki Yoshida^{5

6}, Hiroshi Yoshida^{7

8

9}

Affiliations

¹ Rinku General Medical Center, Izumisano, Osaka, Japan.
² Diabetes Center, Ebina General Hospital, Ebina, Kanagawa, Japan.
³ Department of Endocrinology and Metabolism, Institute of Medicine, University of Tsukuba, Tsukuba, Japan.
⁴ Department of Internal Medicine, Teikyo University School of Medicine, Tokyo, Japan.
⁵ Department of Medical Genetics, Tokyo Medical and Dental University, Tokyo, Japan.
⁶ Department of Life Science and Bioethics, Graduate School of Medicine, Tokyo Medical and Dental University, Tokyo, Japan.
⁷ Section of Internal Medicine of Metabolism and Nutrition, The Jikei University Graduate School of Medicine, Tokyo, Japan.
⁸ Department of General Medicine, The Jikei University Kashiwa Hospital, Chiba, Japan.
⁹ Department of Laboratory Medicine, The Jikei University Kashiwa Hospital, Chiba, Japan.

PMID: 38662591
DOI: 10.1111/eci.14227

Abstract

Background: Numerous epidemiological studies have shown that hypertriglyceridemia is a significant risk factor for cardiovascular diseases (CVD). However, large clinical studies on triglyceride-lowering therapy have yielded inconsistent results. In the current review, we reassess the importance of triglyceride-lowering therapy in preventing CVD based on previous literature and the recently published findings of the PROMINENT trial.

Methods: This narrative review is based on literature and public documents published up to November 2023.

Results: Meta-analyses of trials on peroxisome proliferator-activated receptor α agonists and triglyceride-lowering therapy, including the PROMINENT trial, have indicated that triglyceride-lowering therapy can reduce CVD events. Mendelian randomization studies have also indicated that triglyceride is indeed a true risk factor for coronary artery disease, leaving no doubt about its relationship to CVD. Meanwhile, the negative results from the PROMINENT trial were likely due to the insufficient triglyceride-lowering effect, slight increases in low-density lipoprotein cholesterol and apolipoprotein B, and the inclusion of mostly high-intensity statin users as target patients. It is unlikely that adverse events counteracted the effectiveness of pemafibrate on outcomes. Additionally, pemafibrate has shown positive effects on non-alcoholic fatty liver disease and peripheral artery disease.

Conclusion: Although the PROMINENT trial did not demonstrate the significance of pemafibrate as a triglyceride-lowering therapy in a specific population, it does not necessarily negate the potential benefits of treating hypertriglyceridemia in reducing CVD events. It is necessary to explore appropriate populations that could benefit from this therapy, utilize data from the PROMINENT trial and other databases, and validate findings in real-world settings.

Keywords: CVD event; PPARα agonists; PROMINENT; pemafibrate; triglyceride; type 2 diabetes.

Publication types

Review