Impact of Pemafibrate Therapy on Reducing Small Dense Low-Density-Lipoprotein-Cholesterol Levels in Patients with Hypertriglyceridemia

Background: Small dense LDL-cholesterol is a recently discovered cardiovascular risk factor beyond LDL-cholesterol. Pemafibrate is a novel selective peroxisome proliferator-activated receptor-α modulator that reduces triglyceride levels. Given the significant association between triglycerides and small dense LDL-cholesterol levels, pemafibrate may reduce the levels of small dense LDL-cholesterol. Methods: Patients with hypertriglyceridemia who started pemafibrate therapy and continued it for >3 months between 2018 and 2022 were included in this retrospective study. The levels of small dense LDL-cholesterol, which was estimated using Sampson’s equation, consisting of the LDL-cholesterol and triglyceride levels, were compared between baseline and 3-month follow-up. Results: A total of 98 patients receiving pemafibrate therapy (median age: 63 years, 69 male) were eligible, including 33 patients (34%) who received concomitant statins. Small dense LDL-cholesterol levels decreased significantly during the course of 3-month pemafibrate therapy from 48.9 (IQR: 35.7, 57.9) mg/dL to 38.8 (IQR: 30.0, 45.1) mg/dL, regardless of the concomitant administration of statins (p < 0.001). The rate of cardiovascular events decreased significantly from the pre-treatment 1-year period to the treatment 1-year period (from 13 to 2 events, from 0.133 to 0.021 events per year, incidence rate ratio: 0.16, 95% confidence interval: 0.14–0.17, p < 0.001). Conclusions: Pemafibrate therapy may mitigate the concentrations of small dense LDL-cholesterol autonomously in patients manifesting hypertriglyceridemia within the authentic clinical milieu. The clinical importance of the diminishment in small dense LDL-cholesterol instigated via pemafibrate merits further scrutiny.