Influence of metabolic syndrome factors and insulin resistance on the efficacy of ezetimibe/simvastatin and atorvastatin in patients with metabolic syndrome and atherosclerotic coronary heart disease risk

Jeffrey B Rosen, Christie M Ballantyne, Willa A Hsueh, Jianxin Lin, Arvind K Shah, Robert S Lowe, Andrew M Tershakovec, Jeffrey B Rosen, Christie M Ballantyne, Willa A Hsueh, Jianxin Lin, Arvind K Shah, Robert S Lowe, Andrew M Tershakovec

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).

Figures

Fig. 1
Fig. 1
Percent change from baseline in lipid, lipoprotein, and hs-CRP by treatment and metabolic syndrome/IR subgroup. Error bars = standard error. Arrows indicate percent change from baseline reported for the overall study population [13], with associated value given below the measured parameter for each treatment group. A10/20/40 = atorvastatin 10/20/40 mg; Apo = apolipoprotein; BP = blood pressure [systolic blood pressure (diastolic blood pressure)]; E10/S20(40) = ezetimibe 10 mg/simvastatin 20(40) mg; FG = fasting glucose; HDL-C = high density lipoprotein cholesterol; IR = Homeostasis Model Assessment of Insulin Resistance tertiles; hs-CRP = high-sensitivity C-reactive protein, LDL-C = low- density lipoprotein cholesterol; Ob = abdominal obesity (waist circumference ≥40 inches for males or ≥35 inches for females); TG = triglycerides

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