Ezetimibe/simvastatin 10/40 mg versus atorvastatin 40 mg in high cardiovascular risk patients with primary hypercholesterolemia: a randomized, double-blind, active-controlled, multicenter study.

BACKGROUND: A considerable number of patients with severely elevated LDL-C do not achieve recommended treatment targets, despite treatment with statins. Adults at high cardiovascular risk with hypercholesterolemia and LDL-C ≥ 2.59 and ≤ 4.14 mmol/L (N = 250), pretreated with atorvastatin 20 mg were randomized to ezetimibe/simvastatin 10/40 mg or atorvastatin 40 mg for 6 weeks. The percent change in LDL-C and other lipids was assessed using a constrained longitudinal data analysis method with terms for treatment, time, time-by-treatment interaction, stratum, and time-by-stratum interaction. Percentage of subjects achieving LDL-C < 1.81 mmol/L, < 2.00 mmol/L, or < 2.59 mmol/L was assessed using a logistic regression model with terms for treatment and stratum. Tolerability was assessed. RESULTS: Switching to ezetimibe/simvastatin resulted in significantly greater changes in LDL-C (-26.81% vs.-11.81%), total cholesterol (-15.97% vs.-7.73%), non-HDL-C (-22.50% vs.-10.88%), Apo B (-17.23% vs.-9.53%), and Apo A-I (2.56% vs.-2.69%) vs. doubling the atorvastatin dose (all p ≤ 0.002), but not HDL-C, triglycerides, or hs-CRP. Significantly more subjects achieved LDL-C < 1.81 mmol/L (29% vs. 5%), < 2.00 mmol/L (38% vs. 9%) or < 2.59 mmol/L (69% vs. 41%) after switching to ezetimibe/simvastatin vs. doubling the atorvastatin dose (all p < 0.001). The overall safety profile appeared generally comparable between treatment groups. CONCLUSIONS: In high cardiovascular risk subjects with hypercholesterolemia already treated with atorvastatin 20 mg but not at LDL-C < 2.59 mmol/L, switching to combination ezetimibe/simvastatin 10/40 mg provided significantly greater LDL-C lowering and greater achievement of LDL-C targets compared with doubling the atorvastatin dose to 40 mg. Both treatments were generally well-tolerated. TRIAL REGISTRATION: Registered at clinicaltrials.gov: NCT00782184.