Efficacy and Safety of Ezetimibe Coadministered With Simvastatin in Patients With Primary Hypercholesterolemia: A Randomized, Double-Blind, Placebo-Controlled Trial

Abstract

To compare the efficacy and safety of 10 mg of ezetimibe coadministered with simvastatin with the safety and efficacy of simvastatin monotherapy for patients with hypercholesterolemia. This multicenter double-blind, placebo-controlled, factorial study enrolled 887 patients with hypercholesterolemia (low-density lipoprotein cholesterol [LDL-C], 145-250 mg/dL; triglycerides, < or = 350 mg/dL). Patients were randomized to 1 of 10 treatments--placebo, ezetimibe at 10 mg/d, simvastatin at 10, 20, 40, or 80 mg/d, or simvastatin at 10, 20, 40, or 80 mg/d plus ezetimibe at 10 mg/d for 12 weeks. The study began March 13, 2001, and ended January 8, 2002. The primary efficacy end point was the mean percent change in LDL-C levels from baseline to study end point (last available postbaseline LDL-C measurement) for the pooled ezetimibe/simvastatin group vs the pooled simvastatin monotherapy group. Coadministration of ezetimibe/simvastatin was significantly (P<.001) more effective than simvastatin alone in reducing LDL-C levels for the pooled ezetimibe/simvastatin vs pooled simvastatin analysis and at each specific dose comparison. The decrease in LDL-C levels with coadministration of ezetimibe and the lowest dose of simvastatin, 10 mg, was similar to the decrease with the maximum dose of simvastatin, 80 mg. A significantly (P<.001) greater proportion of patients in the ezetimibe/simvastatin group achieved target LDL-C levels compared with those in the monotherapy group. Treatment with ezetimibe/simvastatin also led to greater reductions in total cholesterol, triglyceride, non-high-density lipoprotein cholesterol, and apolipoprotein B levels compared with simvastatin alone; both treatments increased high-density lipoprotein cholesterol levels similarly. The safety and tolerability profiles for the ezetimibe/simvastatin and monotherapy groups were similar. Through dual inhibition of cholesterol absorption and synthesis, coadministration of ezetimibe/simvastatin offers a highly efficacious and well-tolerated lipid-lowering strategy for treating patients with primary hypercholesterolemia.