Abstract
BACKGROUND: Metabolic syndrome (MetS) and insulin resistance (IR) are increasing in prevalence, are associated with higher risk for coronary heart disease (CHD), and may potentially influence the responses to lipid-altering drug therapy. This study evaluated the effects of MetS factors (abdominal obesity, depleted high-density lipoprotein cholesterol [HDL-C], and elevated triglycerides, blood pressure, and fasting glucose) and IR on ezetimibe/simvastatin and atorvastatin treatment efficacy in patients with MetS. METHODS: This post-hoc analysis of a multicenter, 6-week, double-blind, randomized, parallel group study of 1128 subjects with hypercholesterolemia, MetS, and moderately high/high CHD risk evaluated the effects of baseline MetS factors/IR on percent change from baseline in lipids, apolipoproteins, and high-sensitivity C-reactive protein (hs-CRP), after treatment with the usual starting doses of ezetimibe/simvastatin (10/20 mg) versus atorvastatin (10 mg, 20 mg) and next higher doses (10/40 mg versus 40 mg). RESULTS: Ezetimibe/simvastatin and atorvastatin efficacy was generally consistent across MetS factor/IR subgroups. Ezetimibe/simvastatin produced greater incremental percent reductions in LDL-C, non-HDL-C, apolipoprotein B, total cholesterol, and lipoprotein ratios for all subgroups, and larger percent increases in HDL-C and apolipoprotein AI for all but non-obese and HDL-C ≥ 40 mg/dL subgroups than atorvastatin at the doses compared. Triglycerides, very-LDL-C, and hs-CRP results were more variable but similar between treatment groups. CONCLUSION: The magnitude of lipid-altering effects produced by each treatment regimen was generally similar across all MetS and IR subgroups. Ezetimibe/simvastatin produced greater percent reductions in most lipid fractions than atorvastatin at the dose comparisons studied, and all treatments were generally well tolerated. (Registered at clinicaltrials.gov: NCT00409773).