Effects of Atorvastatin 10 mg and Fenofibrate 200 mg on the Low-Density Lipoprotein Profile in Dyslipidemic Patients: A 12-Week, Multicenter, Randomized, Open-Label, Parallel-Group Study

BACKGROUND: Elevated plasma low-density lipoprotein cholesterol (LDL-C) concentrations are highly atherogenic, especially the small, dense LDL (sdLDL) species. Fenofibrate has been reported to shift the LDL profile by decreasing the sdLDL subfraction and increasing larger LDL subclasses. Atorvastatin, an anti hyperlipidemic agent, has been reported to reduce plasma total cholesterol (TC) and triglyceride (TG) concentrations and thus could modify the LDL profile. OBJECTIVE: The aim of this study was to compare the effects of fenofibrate and atorvastatin on standard lipid concentrations and the LDL profile. METHODS: In this randomized, open-label, parallel-group study, men and women aged 18 to 79 years with type 11 primary dyslipidemia, defined as LDL-C >= 160 and TG 150 to 400 mg/dL, after a 4- to 6-week washout period while eating an appropriate diet, were randomized to receive either atorvastatin 10 mg once daily or fenofibrate 200 mg once daily. Plasma lipid concentrations and cholesterol and apolipoprotein (apo) B (reflecting the LDL particle number) in each LDL subfraction prepared by ultracentrifugation were determined at baseline and after 12 weeks of treatment. Tolerability was assessed using adverse events (AEs) obtained on laboratory analysis and vital sign measurement. Adherence was assessed by Counting unused drug supplies. RESULTS: A total of 165 patients (117 men, 48 women; mean [SD] age, 50.1 [10.7] years; mean TC concentration, 289 mg/dL) were randomized to receive atorvastatin (n = 81.) or fenofibrate (n = 84). Compared with fenofibrate, atorvastatin was associated with a significantly greater mean (SD) percentage decrease in TC (27.0% [12.3%] vs 16.5% [12.9%]; P < 0.001), calculated LDL-C (35.4% [1.5.8%] vs 17.3% [17.2%]; P < 0.001), TC/high-density lipoprotein cholesterol (HDL-C) ratio (29.1% [16.3%] vs 22.9% [15.9%]; P = 0.001), and apoB (30.3% [12.7%] vs 19.6% [15.5%]; P < 0.001). Compared with atorvastatin, fenofibrate was associated with a significantly greater decrease in TG (37.2% [25.9%] vs 20.2% [27.3%]; P < 0.001) and a significantly greater increase in HDL-C concentration (10.4% [15.7%] vs 4.6% [12.1%]; P = 0.017). Fibrinogen concentration was significantly different between the 2 groups (P = 0.002); it was decreased with fenofibrate use (4.6% [23.7%]) and was increased with atorvastatin use (5.7% [23.5%]). Atorvastatin did not markedly affect the LDL distribution; it was associated with a homogeneous decrease in cholesterol and apoB concentrations In all subfractions, whereas fenofibrate was associated with a marked movement toward a normalized LDL profile, shifting the sdLDL subfractions toward larger and less atherogenic particles, particularly in those patients with baseline TG >= 200 mg/dL. No serious AEs related to the Study treatments were reported. A total of 5 AEs were observed in 8 patients, including: abdominal pain, 3 patients (2 in the atorvastatin group and I in the fenofibrate group); abnormal liver function test results, I (fenofibrate); increased creatine phosphokinase activity, 2 (atorvastatin); gastrointestinal disorders, 1 (fenofibrate); and vertigo, 1 (fenofibrate). CONCLUSION: in these dyslipidemic patients, fenofibrate treatment was associated with an improved LDL subfraction profile beyond reduction in LDL-C, particularly in patients. with elevated TG concentration, whereas atorvastatin was associated with equally reduced concentrations of cholesterol and apoB in all LDL subfractions independent of TG concentrations. (Curr Ther Res Clin Exp. 2009;70:71-93) (C) 2009 Excerpta Medica Inc.