Effects of pemafibrate (K-877) on cholesterol efflux capacity and postprandial hyperlipidemia in patients with atherogenic dyslipidemia.

BACKGROUND: Cardiovascular risk is negatively correlated with cholesterol efflux capacity (CEC) from macrophages to high-density lipoproteins (HDLs) and positively correlated with fasting and nonfasting triglyceride-rich lipoproteins (TRLs). Pemafibrate, a novel selective peroxisome proliferator-activated receptor α modulator, robustly decreases the fasting TRL level, increases the HDL cholesterol (HDL-C) level, and improves the atherogenic lipoprotein subclass profile, with an adverse event rate comparable to that of placebo treatment in previous clinical studies.

OBJECTIVE: This study aimed to investigate the effects of pemafibrate on CEC and postprandial hyperlipidemia.

METHODS: Using a single-center, double-blind, randomized, two-by-two crossover design, 33 patients were assigned to receive either 0.4 mg/d pemafibrate (twice daily) or placebo first. The assigned study drug was administered for 4 weeks. Subsequently, the alternate study drug was administered for another 4 weeks. CEC was measured using HDLs obtained from fasting blood samples. A meal tolerance test was performed to examine the postprandial lipid levels at weeks 0, 4, and 8.

RESULTS: CEC, HDL-C, and apolipoprotein A-I levels increased after pemafibrate treatment compared with placebo administration. Moreover, the percent change in CEC was correlated with that of HDL-C and apolipoprotein A-I levels. TRL levels markedly decreased after pemafibrate treatment in both fasting and nonfasting states.

CONCLUSIONS: These findings suggest that pemafibrate enhances reverse cholesterol transport and may retard the progression and even promote the regression of atherosclerosis by comprehensively ameliorating the atherogenic lipid profile.