Effects of fenofibrate and simvastatin on HDL-related biomarkers in low-HDL patients

The objective of the present study was to compare the effects of fenofibrate versus simvastatin on various HDL-related biomarkers in dyslipidemic patients with low HDL-C, in whom it is as yet unclear whether a statin or a fibrate is the most appropriate treatment. Fifty-two patients received either fenofibrate (160 mg/day) or simvastatin (40 mg/day) for 8 weeks in a randomized, double-blind, parallel group trial. Simvastatin effectively lowered plasma LDL-C and apoB levels, but did not change plasma HDL levels and HDL-related biomarkers, except for a small, significant increase in the capacity of plasma to promote SR-BI mediated cholesterol efflux. Fenofibrate did not affect plasma LDL-C levels but lowered triglycerides, and exerted a remarkable HDL-C raising activity (+22%), with patients in the lowest range of HDL-C getting the maximal benefit. The HDL-C raise was associated with a shift of HDL from large to small particles, and from LpA-I to LpA-I:A-II, which might explain the observed increase in the plasma capacity to promote ABCA1 mediated efflux with no changes in SR-BI efflux. The distinct and complementary effects of fenofibrate and simvastatin on lipid parameters and HDL-related biomarkers suggest that a combination therapy with the two drugs in dyslipidemic patients with low HDL would be fully justified.