Antiplatelet effects of micronized fenofibrate in subjects with dyslipidemia

Fibrates produce additional actions such as reduction of inflammatory state, insulin resistance and activation of blood coagulation, along with stimulation of fibrinolysis. It is not known whether fibrates can attenuate platelet activation. Objectives. Evaluation of antiplatelet effects of fenofibrate in dyslipidemic subjects. Patients and methods. In 20 patients (15 males, 5 females) aged 40 to 70 years who had plasma triglycerides >1.7 mmol/l and low-density lipoprotein (LDL) cholesterol >3.4 mmol/l without diabetes, we determined plasma levels of platelet markers, soluble CD40 ligand (sCD40L) and P-selectin, both in peripheral blood and samples collected every 1 minute from sites of microvascular injury prior to and following a onemonth administration of micronized fibrate (160 mg/d). Results. Neither of platelet activation markers was altered following fenofibrate. We identified 7 subjects who had a significant decrease (14–21%) in velocity of the sCD40L and P-selectin release after fenofibrate (p <0.05). This subgroup was characterized by increased body mass, and posttreatment greater reduction in triglycerides and increase in high-density lipoprotein (HDL) cholesterol (p <0.05). A decrease in the release of platelet markers was associated with a greater posttreatment reduction in plasma 8-isoprostane levels (p = 0.006). Conclusions. In 1/3 of dyslipidemic subjects without diabetes, there is a decrease in platelet activation at the site of microvascular injury following a one-month administration of micronized fenofibrate. This effect can be found in individuals in whom the fibrate induced the greatest reduction in triglycerides and increase in HDL cholesterol. Moreover, antiplatelet effect of fenofibrate was associated with reduced oxidative stress.