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Ezetimibe and Fenofibrate in Patients With Mixed Hyperlipidemia - Ezetimibe and Fenofibrate in Patients With Mixed Hyperlipidemia
Description:
The goal of the trial was to evaluate the safety and efficacy of ezetimibe coadministered with fenofibrate in patients with mixed hyperlipidemia.
Study Design
Study Design:
Patients Screened: 1,675
Patients Enrolled: 625
Mean Follow Up: 12 weeks
Mean Patient Age: 18-75 years (mean 54 years)
Patient Populations:
Age 18-75 years, mixed hyperlipidemia, and no coronary heart disease (CHD), CHD-equivalent disease (except for type 2 diabetes), or 10-year CHD risk >20%
Exclusions:
Homozygous familial hypercholesterolemia; type I or V hyperlipidemia; treatment with LDL apheresis; congestive heart failure; uncontrolled cardiac arrhythmia; unstable hypertension; pancreatitis; inadequately controlled diabetes; gallbladder, renal, or active liver disease; uncontrolled endocrine or metabolic disease known to influence serum lipids or lipoproteins; pregnancy or lactation; and contraindicated medications that cannot be discontinued
Primary Endpoints:
Percent change in LDL cholesterol from baseline to 12 weeks for the comparison of fenofibrate + ezetimibe versus fenofibrate alone
Secondary Endpoints:
Percent change in total cholesterol, triglyceride and non-HDL cholesterol, HDL cholesterol, apo-B, and apo A-I from baseline to 12 weeks
Drug/Procedures Used:
Patients were randomized in a 1:3:3:3 ratio to once daily treatment with placebo (n=64), ezetimibe 10 mg (n=187), fenofibrate 160 mg (n=189), and fenofibrate 160 mg plus ezetimibe 10 mg (n=185). Treatment lasted for 12 weeks.
Principal Findings:
National Cholesterol Education Program Adult Treatment Panel III criteria were present in 54% of patients, and diabetes in 16%. Baseline lipid measures were similar in all treatment groups. Study drug discontinuation was higher in all three of the active treatment groups compared with the placebo group (6.4% for ezetimibe alone, 6.3% for fenofibrate, 7.0% for combination group, and 1.6% for placebo).
Reduction in low-density lipoprotein (LDL) was greater in the combination group compared with either the fenofibrate alone, ezetimibe group, or the placebo group (-20.4% vs. -5.5%, -13.4%, and +0.2%, respectively, p<0.001 each). Likewise, the reduction in other lipid parameters was also greater in the combination group, including total cholesterol (-22.4% vs. -10.8%, -11.8%, and +0.2%, respectively, p<0.001 each) and apolipoprotein-B (apo-B) (-26.1% vs. -15.2%, -11.3%, and +1.2%, respectively, p<0.001 each). Reductions in C-reactive protein (CRP) were greater in the combination group (-27.3%) and the fenofibrate alone group (-28.0%) compared with the ezetimibe alone group (-6.1%) or the placebo group (+9.1%).
More patients in the combination group met LDL and nonhigh-density lipoprotein (non-HDL) goals compared with either ezetimibe or fenofibrate alone or placebo. There were no cases of elevated creatine kinase (CK) >10x, myopathy, or rhabdomyolysis in any group. There was no difference in the frequency of myalgia.
Interpretation:
Among patients with mixed hyperlipidemia, co-administration of ezetimibe with fenofibrate was associated with greater reductions in LDL cholesterol at 12 weeks compared with either therapy alone or with placebo. Improvements were noted in other lipid parameters with combination therapy, including total cholesterol and apo B reductions, as well as reductions in CRP, a marker of inflammation. Despite the administration of two medications, the adverse event rates were similar, with no difference in myalgia and no cases of large CK elevations or rhabdomyolysis.
References:
Farnier M, Freeman MW, Macdonell G, et al. Efficacy and safety of the coadministration of ezetimibe with fenofibrate in patients with mixed hyperlipidaemia. Eur Heart J 2005; 26:897-905.
Keywords: Fenofibrate, Inflammation, Hyperlipidemia, Familial Combined, Creatine Kinase, Cholesterol, LDL, Diabetes Mellitus, Type 2, Coronary Disease, Hypercholesterolemia, Rhabdomyolysis, Lipoproteins, LDL, C-Reactive Protein, Azetidines, Hypolipidemic Agents, Myalgia
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