Prospective randomized comparative study of the effect of pemafibrate add-on or double statin dose on small dense low-density lipoprotein-cholesterol in patients with type 2 diabetes and hypertriglyceridemia on statin therapy.

AIMS/INTRODUCTION: Small dense low-density lipoprotein (sdLDL) is a more potent atherogenic lipoprotein than LDL. As sdLDL-cholesterol (C) levels are determined by triglyceride and LDL-C levels, pemafibrate and statins can reduce sdLDL-C levels. However, it remains unclear whether adding pemafibrate or increasing statin doses would more effectively reduce sdLDL-C levels in patients receiving statin therapy. MATERIALS AND METHODS: A total of 97 patients with type 2 diabetes and hypertriglyceridemia who were treated with statins were randomly assigned to the pemafibrate 0.2 mg/day addition or statin dose doubled, and followed for 12 weeks. sdLDL-C was measured by our established homogenous assay. RESULTS: The percentage and absolute reductions of sdLDL-C levels were significantly greater in the pemafibrate add-on group than the statin doubling group (-32.8 vs -8.1%; -16 vs -3 mg/dL, respectively). Triglyceride levels were reduced only in the pemafibrate add-on group (-44%), and LDL-C levels were reduced only in the statin doubling group (-8%), whereas levels of non-high-density lipoprotein-C and apolipoprotein B were similarly decreased (7-9%) in both groups. The absolute reductions of sdLDL-C levels were closely associated with decreased triglyceride, LDL-C, non-high-density lipoprotein-C and apolipoprotein B. In the subgroup analysis, the effect of pemafibrate add-on on sdLDL-C reductions was observed irrespective of baseline lipid parameters or statin type. No serious adverse effects were observed in both groups. CONCLUSIONS: In patients with type 2 diabetes and hypertriglyceridemia, the addition of pemafibrate to a statin is superior to doubling a statin in reducing sdLDL-C without increasing adverse effects.