A One-Year Retrospective Observational Study Reveals the Transient Nature of Pemafibrate-Induced LDL-C Elevation:...

Pemafibrate, a selective peroxisome proliferator-activated receptor-α modulator (SPPARMα), is widely used for hypertriglyceridemia; however, concerns persist regarding its potential to elevate low-density lipoprotein cholesterol (LDL-C). Previous studies monitored LDL-C for only 3-6 months, leaving the long-term trajectory unclear. This one-year retrospective observational study aimed to determine whether pemafibrate-induced LDL-C elevation is sustained or transient and to identify factors associated with this response.

A total of 110 patients receiving pemafibrate (0.1-0.2 mg/day; standard dose 0.2 mg/day) were followed for one year. Serial lipid changes were analyzed, and predictors of LDL-C elevation were evaluated using multivariate regression.

Triglyceride decreased markedly from 378.6 ± 248.7 to 191.5 ± 144.4 mg/dL (P < 0.001). LDL-C increased from 120.5 ± 30.6 to 129.7 ± 34.3 mg/dL at 3 months (P < 0.05), representing the peak of LDL-C elevation. Thereafter, LDL-C gradually declined and showed no statistically significant difference from the baseline at 12 months, demonstrating a characteristic transient "rise-and-return" pattern. Lower baseline LDL-C, lower HDL-C, and higher triglycerides were associated with greater LDL-C elevation, while statin use showed no significant association. Low baseline LDL-C was the strongest predictor in multivariate analysis.

This study is the first to document the full one-year LDL-C trajectory under pemafibrate, revealing a transient "rise-and-return" pattern. LDL-C elevation peaks at approximately 3 months and returns to baseline by one year, indicating that the increase is temporary rather than persistent. These findings refine the understanding of pemafibrate's lipid effects and support its long-term safety profile.