Comparative effects of simvastatin and atorvastatin in hypercholesterolemic patients with characteristics of metabolic syndrome

Abstract

Background: Hypercholesterolemic patients with metabolic syndrome (MS) are at high risk for coronary heart disease. The National Cholesterol Education Program (NCEP) Adult Treatment Panel III (ATP III) guidelines provide the option of aggressively lowering low-density lipoprotein cholesterol (LDL-C) in hypercholesterolemic patients with MS. Objective: The lipid-modifying efficacy of simvastatin and atorvastatin in hypercholesterolemic patients with MS as defined by NCEP ATP III was assessed. Methods: A post hoc subgroup analysis was performed on data from a 36-week, multicenter (54 sites worldwide), randomized, double-blind, parallel-group, dose-escalation (forced-titration) study designed to assess the effects of simvastatin (40–80 mg) and atorvastatin (20–80 mg) on high-density lipoprotein cholesterol (HDL-C) and apolipoprotein (apo) A-I levels in patients with LDL-C ≥ 160 mg/dL. Patients were classified as having MS if they met ≥3 of the following criteria: (1) triglyceride (TG) level ≥150 mg/dL; (2) HDL-C <40 mg/dL (men) or <50 mg/dL (women); (3) secondary diagnosis of type 2 diabetes mellitus and/or taking antidiabetic medication and/or fasting serum glucose (FSG) level ≥110 mg/dL; (4) secondary diagnosis of hypertension and/or taking antihypertensive medication and/or systolic blood pressure (SBP)/diastolic blood pressure (DBP) ≥130/≥85 mm Hg; and (5) body mass index (BMI) ≥30 kg/m 2 (surrogate for waist circumference). Results: Of 808 evaluable patients, 212 (26.2%) were classified as having MS at baseline. Compared with the non-MS subgroup, MS patients were slightly older and more likely to be female. They also had higher BMI, SBP/DBP, FSG, and TG levels, and lower HDL-C and apo A-I levels than non-MS patients. The simvastatin group contained 99 patients; the atorvastatin group, 113 patients. Both drugs produced large reductions in total cholesterol, LDL-C, non-HDL-C, TG, and apo B, with atorvastatin producing slightly greater reductions in TG. However, simvastatin consistently produced larger increases in HDL-C and apo A-I than atorvastatin, especially at higher doses. After 36 weeks of treatment, 47.7% and 48.5% in the simvastatin and atorvastatin groups, respectively, no longer met ≥3 of the MS criteria. Conclusions: In hypercholesterolemic patients with characteristics of MS, simvastatin and atorvastatin had comparable beneficial effects on apo B-containing atherogenic lipids and lipoproteins, and MS status was effectively modified by both drugs. However, although atorvastatin produced slightly larger decreases in TG, simvastatin produced larger increases in HDL-C.