Abstract and Introduction
Abstract
Background: Mixed hyperlipidemia is characterized by elevated low-density lipoprotein cholesterol (LDL-C), triglyceride (TG), and TG-rich lipoprotein levels.
Methods: In a multicenter, randomized, double-blind, placebo-controlled, parallel arm trial, eligible patients were 18 to 79 years of age, with mixed hyperlipidemia (LDL-C 130-220 mg/dL, TG 150-500 mg/dL). Patients with type 2 diabetes were limited to those with LDL-C of 100 to 180 mg/dL. Patients (N = 611) were randomized in a 3:3:3:1 ratio to one of 4 treatment arms for 12 weeks: ezetimibe/simvastatin 10/20 mg (EZE/SIMVA) + fenofibrate 160 mg (FENO), EZE/SIMVA 10/20 mg, FENO 160 mg, or placebo. The primary objective was to evaluate the LDL-Clowering efficacy of EZE/SIMVA + FENO versus FENO monotherapy.
Results: Low-density lipoprotein cholesterol level was significantly (P < .05) reduced with EZE/SIMVA + FENO (−45.8%) compared with FENO (−15.7%) or placebo (−3.5%), but not when compared with EZE/SIMVA (−47.1%). High-density lipoprotein cholesterol and apolipoprotein A-I levels were significantly increased with EZE/SIMVA + FENO (18.7% and 11.1%, respectively) treatment compared with EZE/SIMVA (9.3% and 6.6%) or placebo (1.1% and 1.6%), but not when compared with FENO (18.2% and 10.8%). Triglyceride, nonhigh-density lipoprotein cholesterol, and apolipoprotein B levels were significantly reduced with EZE/SIMVA + FENO (−50.0%, −50.5%, and −44.7%, respectively) versus all other treatments. Treatment with EZE/SIMVA + FENO was generally well tolerated with a safety profile similar to the EZE/SIMVA and FENO therapies.
Conclusions: Coadministration of EZE/SIMVA + FENO effectively improved the overall atherogenic lipid profile of patients with mixed hyperlipidemia. Clinical trial registry number: NCT 00093899 (http://www.ClinicalTrials.gov).
Introduction
The presence of both hypercholesterolemia and hypertriglyceridemia is the hallmark of mixed hyperlipidemia. Dietary modification and increased physical activity are the first recommended therapy to modify these lipid abnormalities, but a lipid-lowering drug is often indicated, especially in the more severe dyslipidemias. The National Cholesterol Education Program Adult Treatment Panel III (NCEP ATP III) guidelines recommend combining drug therapies to achieve the lipid treatment targets for mixed hyperlipidemia.
In previous studies, the coadministration of simvastatin 20 mg (SIMVA) and fenofibrate 160 mg (FENO) significantly reduced lipid parameters including low-density lipoprotein cholesterol (LDL-C), triglycerides (TG), and nonhigh-density lipoprotein cholesterol (HDL-C), and increased HDL-C compared with SIMVA 20 mg alone over 12 weeks in patients with mixed hyperlipidemia. Moreover, in a similar patient population, the lipid-lowering effects on LDL-C, TG, and nonHDL-C were significantly greater with the coadministration of ezetimibe (EZE) and FENO compared to each monotherapy, and coadministration and FENO alone also produced comparable increases in LDL particle size and HDL-C. In an extension to this study, the lipid-altering effects of coadministered EZE and FENO were maintained for up to 60 weeks. It has been demonstrated that a single tablet containing ezetimibe and simvastatin (EZE/SIMVA) significantly decreased apolipoprotein B (apo B)containing lipoproteins and modestly improved HDL-C and TG when compared with either treatment alone in patients with primary hypercholesterolemia. In view of the limited treatment options available to treat mixed hyperlipidemia, the current study was performed to examine the efficacy and tolerability of EZE/SIMVA and FENO in patients with mixed hyperlipidemia.