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

• Main Authors: Hing Ling Paul, Civeira Fernando, Dan Andrei, Hanson Mary E, Massaad Rachid, De Tilleghem Celine, Milardo Christopher, Triscari Joseph
• Format: Article
• Language: English
• Published: BMC 2012-01-01
• Series: Lipids in Health and Disease
• Subjects: Ezetimibe/simvastatin; Atorvastatin; High cardiovascular risk; Primary hypercholesterolemia; Lipid-lowering
• Online Access: http://www.lipidworld.com/content/11/1/18

<p>Abstract</p> <p>Background</p> <p>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.</p> <p>Results</p> <p>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 <it>p </it>≤ 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 <it>p </it>< 0.001). The overall safety profile appeared generally comparable between treatment groups.</p> <p>Conclusions</p> <p>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.</p> <p>Trial registration</p> <p>Registered at clinicaltrials.gov: <a href="http://www.clinicaltrials.gov/ct2/show/NCT00782184">NCT00782184</a></p>