COPENHAGEN — A combination of ezetimibe and simvastatin provides additional lipid-modifying benefits compared with rosuvastatin monotherapy among patients with type 2 diabetes or with metabolic syndrome without diabetes, Dr. Alberico L. Catapano reported at the annual meeting of the European Association for the Study of Diabetes.
“Overall, ezetimibe/simvastatin, a single-tablet, dual-cholesterol inhibitor [Vytorin, Merck], offers an effective and well-tolerated lipid-modifying option for the treatment of hypercholesterolemia in patients with type 2 diabetes and metabolic syndrome,” said Dr. Catapano, of the department of pharmacological sciences at the University of Milan.
In a post-hoc analysis of data from a multicenter, double-blind, randomized, parallel-group, 6-week study sponsored by Merck & Co., 375 patients with type 2 diabetes, 840 with metabolic syndrome but without diabetes, 1,722 with neither condition, and 22 who could not be placed in a category because of missing data were randomized to one of six treatment groups: ezetimibe/simvastatin (E/S) in doses of 10 mg/20 mg (respectively), 10 mg/40 mg, or 10 mg/80 mg; or rosuvastatin (Crestor, AstraZeneca) in doses of 10, 20, or 40 mg. All had hypercholesterolemia, defined as an LDL-cholesterol level of 145–249 mg/dL with triglycerides at or below 350 mg/dL.
Among the whole cohort of 2,959 patients, significant reductions in LDL cholesterol from baseline were seen among the E/S group at the usual starting, next highest, and maximum dosing levels. (See chart.)
Across all doses, the difference in LDL-cholesterol reduction between E/S and rosuvastatin was significant for the whole cohort (55.8% vs. 51.6%). Consistent with that, LDL-cholesterol lowering was also greater with E/S among the patients with type 2 diabetes (58.5% vs. 54.2%), nondiabetics with metabolic syndrome (55% vs. 51.8%), and those with neither (55.6% vs. 51%), Dr. Catapano reported.
Overall, 95.3% of the E/S group, compared with 92.1% of the rosuvastatin group, attained the recommended LDL goals of less than 100 mg/dL for the diabetics, 130 mg/dL for the nondiabetics with metabolic syndrome, or 160 mg/dL for the group with neither. A total of 88.2% of the E/S patients versus 81.9% of the rosuvastatin patients achieved an LDL-cholesterol level of less than 100 mg/dL, whereas 45.3% vs. 29.5% reached an LDL-cholesterol level of less than 70 mg/dL. All of these differences were significant, he said.
Reductions in total cholesterol, non-HDL cholesterol, apolipoprotein B, and triglycerides were also significantly greater with E/S, whereas there were no significant differences between the two treatments in HDL cholesterol, or high-sensitivity C-reactive protein.
Both drugs were well tolerated in all patient groups, with similar rates of drug-related adverse events (8.1% with E/S vs. 7.4% with rosuvastatin) and discontinuations because of adverse events (2.2% for both drugs). Proteinuria was higher at baseline in the rosuvastatin group and among those with diabetes, Dr. Catapano noted.
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