VAP II analysis of lipoprotein subclasses in mixed hyperlipidemic patients on treatment with ezetimibe/simvastatin and fenofibrate

This analysis evaluates the effects on lipoprotein subfractions and LDL particle size of ezetimibe/simvastatin with or without coadministration of fenofibrate in patients with mixed hyperlipidemia. This multicenter, double-blind, placebo-controlled, parallel-group study included 611 patients aged 18 - 79 years randomized in 1: 3: 3: 3 ratios to one of four 12 week treatment groups: placebo; ezetimibe/simvastatin 10/20 mg/day; fenofibrate 160 mg/day; or ezetimibe/simvastatin 10/20 mg/day; fenofibrate 160 mg/day. At baseline and study endpoint, cholesterol associated with VLDL, intermediate density lipoprotein ( IDL), LDL, and HDL subfractions was quantified using the Vertical Auto Profile II method. LDL particle size was determined using segmented gradient gel electrophoresis. Whereas fenofibrate reduced cholesterol mass within VLDL and IDL, and shifted cholesterol from dense LDL subfractions into the more buoyant subfractions and HDL, ezetimibe/simvastatin reduced cholesterol mass within all apolipoprotein B-containing particles without significantly shifting the LDL particle distribution profile. When administered in combination, the effects of the drugs were complementary, with more-pronounced reductions in VLDL, IDL, and LDL, preferential loss of more-dense LDL subfractions, and increased HDL, although the effects on most lipoprotein subfractions were not additive. Thus, ezetimibe/simvastatin 1 fenofibrate produced favorable effects on atherogenic lipoprotein subclasses in patients with mixed hyperlipidemia. - Farnier, M., I. Perevozskaya, W. V. Taggart, D. Kush, and Y. B. Mitchel. VAP II analysis of lipoprotein subclasses in mixed hyperlipidemic patients on treatment with ezetimibe/simvastatin and fenofibrate. J. Lipid Res. 2008. 49: 2641-2647.