Effects of Pemafibrate and Eicosapentaenoic Acid Ethyl Ester on Endothelial Function in Patients With Hypertriglyceridemia and Coronary Artery Disease: A Study Protocol for a Multicenter, Open-Label Randomised Controlled Trial

Despite intensive low-density lipoprotein cholesterol-lowering therapies effectively reducing cardiovascular events, residual cardiovascular risks remain significant, with hypertriglyceridemia being an important contributing factor. Pemafibrate, a novel selective peroxisome proliferator-activated receptor alpha modulator, has shown strong triglyceride-lowering effects and potential vascular benefits. Similarly, eicosapentaenoic acid ethyl ester (EPA) has demonstrated cardiovascular protective effects, particularly in patients with hypertriglyceridemia. However, the comparative impact of these agents on endothelial function, a key marker of atherosclerotic progression, has not been thoroughly evaluated in patients with coronary artery disease (CAD). The PRIME (PRospective comparIson of peMafibrate and Eicosapentaenoic acid ethyl ester on vascular functions for hypertriglyceridemia) trial is a multi-center, open-label, randomised trial designed to compare the effects of pemafibrate and EPA on endothelial function in patients with CAD and hypertriglyceridemia. Patients receiving statin therapy with fasting triglyceride levels ≥150 mg/dL will be randomised into two groups: pemafibrate (0.2 mg/day, with possible dose escalation to 0.4 mg/day) or EPA (1800 mg/day, with possible dose escalation to 2700 mg/day). Endothelial function will be assessed with reactive hyperemia index (RHI). The primary endpoint is the change in RHI at 12 weeks. The secondary endpoints include the changes in RHI at 24 weeks, correlations between changes in RHI and changes in lipid biomarkers, and changes in biochemical parameters at 12 and 24 weeks. This study investigates the comparative effects of pemafibrate and EPA on endothelial function, addressing an unmet need in managing residual cardiovascular risk in patients with CAD. The findings will contribute to the optimisation of treatment strategies in patients with CAD and hypertriglyceridemia.