Objective: To assess the lipid-altering efficacy and safety of ezetimibe/simvastatin single tablet product compared with rosuvastatin at the approved usual starting, next highest, and maximum doses.
Research design and methods: Double-blind, multicenter, 6-week, parallel-group study in hypercholesterolemic patients (n = 2959). Patients were randomized based on stratification by low-density lipoprotein cholesterol (LDL-C) levels to ezetimibe/simvastatin or rosuvastatin, respectively, at the usual starting (10/20 or 10 mg/day), the next highest (10/40 or 20 mg/day), and maximum doses (10/80 or 40 mg/day).
Results: At all doses and across doses, ezetimibe/simvastatin reduced LDL-C levels significantly more (52-61%) than rosuvastatin (46-57%; p < or = 0.001). Significantly greater percentages of all patients (p < 0.001) and high risk patients (p < or = 0.005) attained LDL-C levels < 70 mg/dL (1.8 mmol/L) following ezetimibe/simvastatin treatment compared with rosuvastatin at the prespecified doses and across doses. Ezetimibe/simvastatin also produced significantly greater reductions in total cholesterol (p < 0.001), non-high-density lipoprotein cholesterol (p < 0.001), lipid ratios (p < or = 0.003), and apolipoprotein B (p < 0.05). Reductions in triglycerides were significantly greater with ezetimibe/simvastatin than rosuvastatin at the usual starting (p = 0.004) and next highest (p = 0.006) doses, and across all doses (p < 0.001). Increases in high-density lipoprotein cholesterol, and decreases in high sensitivity C reactive protein (hsCRP) were similar between treatment groups. Safety profiles were comparable for both treatments; however, the percent of patients with proteinuria was significantly higher following rosuvastatin treatment than ezetimibe/simvastatin, respectively at 10 mg versus 10/20 mg/day (p = 0.004) and 40 mg versus 10/80 mg/day (p < 0.001).
Conclusion: Ezetimibe/simvastatin was more effective than rosuvastatin in LDL-C lowering, and provided greater or comparable improvements in other lipid measures and hsCRP at the approved usual starting, next highest, and maximum doses in hypercholesterolemic patients. Although the doses compared in this study were not equivalent on a milligram basis, the results provide clinically relevant information regarding the use of these drugs for initial therapy and for subsequent use at higher doses when appropriate. Both treatments were generally well-tolerated; however, this study was not powered nor of sufficient duration to assess the prevalence of rare clinical adverse effects. Overall, ezetimibe/simvastatin offers an effective and tolerable treatment option for lipid management. An assessment of its full clinical benefit awaits evaluation in longer-term clinical studies.
Trial registration: ClinicalTrials.gov NCT00090298.