Efficacy and safety of the coadministration of ezetimibe/simvastatin with fenofibrate in patients with mixed hyperlipidemia.

Background Mixed hyperlipidemia is characterized by elevated low-density lipoprotein cholesterol (LDL-C), triglycericle (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/c1L, 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-C-lowering 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 1- 15.7%) or placebo (-3.5%), but not when compared with EZE/SIMVA (-47. 1 %). Highdensity lipoprotein cholesterol and apolipoprotein A-1 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 (11 % and 1.6%), but not when compared with FENO (18.2% and 10.8%). Triglyceride, non-high-density lipoprotein cholesterol, and apolipoprotein B levels were significantly reduced with EZE/5IMVA + 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).