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

• Published in: The American heart journal 2007-02, Vol.153 (2), p.335.e1-335.e8
• Main Authors: Farnier, Michel, MD, PhD, Roth, Eli, MD, Gil-Extremera, Blas, MD, Mendez, Gustavo F., MD, Macdonell, Geraldine, MHA, Hamlin, Constance, BS, Perevozskaya, Inna, PhD, Davies, Michael J., PhD, Kush, Debra, MBA, Mitchel, Yale B., MD
• Format: Article
• Language: English
• Subjects: Apolipoproteins; Azetidines - administration & dosage; Azetidines - adverse effects; Cardiovascular; Cardiovascular disease; Cholesterol; Diabetes; Double-Blind Method; Drug Combinations; Drug therapy; Drug Therapy, Combination; Ezetimibe, Simvastatin Drug Combination; Female; Fenofibrate - administration & dosage; Fenofibrate - adverse effects; Gallbladder; Humans; Hyperlipidemias - drug therapy; Hypolipidemic Agents - administration & dosage; Hypolipidemic Agents - adverse effects; Lipids; Lipoproteins; Male; Metabolic disorders; Middle Aged; Simvastatin - administration & dosage; Simvastatin - adverse effects
• ISSN: 0002-8703; 1097-6744
• DOI: 10.1016/j.ahj.2006.10.031

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-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 (−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, non–high-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 ).