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), 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).
Farnier
Michel
M
Point Medical, Dijon, France. michelfarnier@nerim.net
Roth
Eli
E
Gil-Extremera
Blas
B
Mendez
Gustavo F
GF
Macdonell
Geraldine
G
Hamlin
Constance
C
Perevozskaya
Inna
I
Davies
Michael J
MJ
Kush
Debra
D
Mitchel
Yale B
YB
D001384:Azetidines / Q000008:administration & dosage* / Q000009:adverse effects; D004311:Double-Blind Method; D004338:Drug Combinations; D004359:Drug Therapy, Combination; D000069499:Ezetimibe, Simvastatin Drug Combination; D005260:Female; D011345:Fenofibrate / Q000008:administration & dosage* / Q000009:adverse effects; D006801:Humans; D006949:Hyperlipidemias / Q000188:drug therapy*; D000960:Hypolipidemic Agents / Q000008:administration & dosage* / Q000009:adverse effects; D008297:Male; D008875:Middle Aged; D019821:Simvastatin / Q000008:administration & dosage* / Q000009:adverse effects
D001384:Azetidines; D004338:Drug Combinations; D000069499:Ezetimibe, Simvastatin Drug Combination; D000960:Hypolipidemic Agents; D019821:Simvastatin; D011345:Fenofibrate