OBJECTIVE: To compare the efficacy and safety of the recommended usual starting and next highest doses of ezetimibe/ simvastatin and atorvastatin in patients with type 2 diabetes mellitus and hypercholesterolemia. PATIENTS AND METHODS: This double-blind, multicenter study (June 22 to December 7, 2005) consisted of adult patients randomized to the recommended usual starting (ezetimibe/simvastatin, 10/20 mg/d, vs atorvastatin, 10 or 20 mg/d) or next highest (ezetimibe/simvastatin, 10/40 mg/d, vs atorvastatin, 40 mg/d) doses. Efficacy end points included percent changes from baseline in low-density lipoprotein cholesterol (LDL-C) levels (primary) and proportion of patients attaining LDL-C levels less than 70 mg/dL (secondary). RESULTS: A total of 1229 patients participated in the study. Significantly greater mean reductions were found in LDL-C levels with ezetimibe/simvastatin, 10/20 mg/d (-53.6%; 95% confidence interval [CI], -55.4% to -51.8%), than with atorvastatin, 10 mg/d (-38.3%; 95% CI, -40.1% to -36.5%; P<.001) or 20 mg/d (-44.6%; 95% CI, -46.4% to -42.8%; P<.001), and with ezetimibe/simvastatin, 10/40 mg/d (-57.6%; 95% CI, -59.4% to -55.8%), vs atorvastatin, 40 mg/d (-50.9%; 95% CI, -52.7% to -49.1%; P<.001). Ezetimibe/simvastatin was also superior to atorvastatin in attainment of LDL-C levels less than 70 mg/dL (P<.001 for all dose comparisons). Significantly better improvements with ezetimibe/simvastatin than with atorvastatin (P≤.001) were observed for total cholesterol, high-density lipoprotein cholesterol, and non-high-density lipoproteln cholesterol. Ezetimibe/ simvastatin, 10/20 mg/d, reduced high-sensitivity C-reactive protein and triglyceride levels significantly more than atorvastatin, 10 mg/d (P=.02), with comparable reductions at other doses. Incidences of clinical adverse events, including serious drug-related and prespecified gastrointestinal-, gallbladder-, and hepatitis-related allergic reactions or rash events, and laboratory adverse events, including repeated elevation of hepatic transaminases or creatine kinase levels, were similar for both treatments. CONCLUSION: Ezetimibe/simvastatin provided additional lipid-modifying benefits over atorvastatin monotherapy at the recommended usual starting and next highest doses in patients with type 2 diabetes. Both treatments were generally well tolerated.
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