A 16-week fenofibrate treatment increases LDL particle size in type IIA dyslipidemic patients

The objective of the present study was to compare the effects of a 16-week pharmacotherapy with fenofibrate (200 mg) or pravastatin (initially 20 mg for 8-weeks and, if necessary, increased to 40 mg) on low density lipoprotein (LDL) particle size assessed by gradient gel electrophoresis among patients with type IIa dyslipidemia.

For that purpose, type IIa dyslipidemic patients (cholesterol, 7.45+/-1.18 (S.D.) mmol/l; LDL cholesterol, 5.57+/-1.16 mmol/l; triglycerides (TGs), 1.66+/-0.43 mmol/l) were randomized to either fenofibrate (n=36) or pravastatin (n=43) therapy for 16 weeks. Fasting plasma lipoprotein levels as well as the LDL peak particle size (using 2-16% polyacrylamide gel electrophoresis) were assessed at baseline and after the 16-week treatment period.

Whereas significant improvements in the plasma lipoprotein-lipid variables were observed with both fenofibrate and pravastatin treatments, LDL peak particle size was only significantly increased with fenofibrate therapy (+2.11+/-5.18 A, P<0.05). Among patients under fenofibrate therapy, changes in TG levels were negatively associated with changes in LDL peak particle size (r=-0.54, P<0.0007), whereas no such association was found in pravastatin-treated patients. The prevalence of patients with small, dense LDL particles (as defined by LDL particle diameter <255.5 A) was reduced from 69.4 to 30.6% (P<0.05) among fenofibrate-treated patients as opposed to 81.4 to 72.1% (NS) in patients who received pravastatin.

As pravastatin treatment had no effect on LDL size, it is suggested that the additional effect of fenofibrate therapy on LDL size may contribute to reduce the risk of coronary heart disease (CHD) beyond what can be expected from the reduction in LDL cholesterol concentration in type IIa dyslipidemic patients.