Efficacy and Safety of Ezetimibe Added on to Atorvastatin (20 mg) Versus Uptitration of Atorvastatin (to 40 mg) in Hypercholesterolemic Patients at Moderately High Risk for Coronary Heart Disease^†

The aim of this study was to evaluate the efficacy and safety of ezetimibe 10 mg added to atorvastatin 20 mg compared with doubling atorvastatin to 40 mg in patients with hypercholesterolemia at moderately high risk for coronary heart disease who did not reach low-density lipoprotein (LDL) cholesterol levels <100 mg/dl with atorvastatin 20 mg. In this 6-week, multicenter, double-blind, randomized, parallel-group study, 196 patients treated with atorvastatin 20 mg received atorvastatin 20 mg plus ezetimibe 10 mg or atorvastatin 40 mg for 6 weeks. Adding ezetimibe 10 mg to atorvastatin 20 mg produced significantly greater reductions in LDL cholesterol than increasing atorvastatin to 40 mg (−31% vs −11%, p <0.001). Significantly greater reductions were also seen in non-high-density lipoprotein cholesterol, total cholesterol, and apolipoprotein B (p <0.001). Significantly more patients reached LDL cholesterol levels <100 mg/dl with atorvastatin 20 mg plus ezetimibe compared with atorvastatin 40 mg (84% vs 49%, p <0.001). The 2 treatment groups had comparable results for high-density lipoprotein cholesterol, triglycerides, apolipoprotein A-I, and high-sensitivity C-reactive protein. The incidences of clinical and laboratory adverse experiences were generally similar between groups. In conclusion, the addition of ezetimibe 10 mg to atorvastatin 20 mg was generally well tolerated and resulted in significantly greater lipid-lowering efficacy compared with doubling atorvastatin to 40 mg in patients with hypercholesterolemia at moderately high risk for coronary heart disease.

• † Conflicts of interest: Dr. Conard served as a consultant and advisor for Merck & Company and Merck/Schering-Plough. Dr. Bays received research grants from Amylin, San Diego, California, Amgen, Thousand Oaks, California, J&J, Langhorne, Pennsylvania, Aegerion, Bridgewater, New Jersey, Abbott, Chicago, Illinois, Arena Pharmaceuticals, San Diego, California, GlaxoSmithKline (Glaxo), London, UK, Hoffmann LaRoche, Nutley, New Jersey, Merck, Whitehouse Station, New Jersey, MSP, Kenilworth, New Jersey, Metabolex, San Jose, California, Schering-Plough, Kenilworth, New Jersey, Orexigen, San Diego, California, Reliant, Liberty Corner, New Jersey, Sciele, Atlanta, Georgia, Takeda, Osaka, Japan, TAP, Lake Forest, Illinois, and Vivus, Mountain View, California; received speakers' honoraria from Abbott, Daiichi Sankyo, Tokyo, Japan, GlaxoSmithKline, Reliant, Merck & Company, Merck/Schering-Plough, and Schering-Plough; received honoraria from Abbott, AstraZeneca, London, UK (Wilmington, Delaware, US Headquarters), Daiichi Sankyo, GlaxoSmithKline, Reliant, Merck & Company, Merck/Schering-Plough, and Schering-Plough; and served as a consultant and advisor for Abbott, GlaxoSmithKline, Metabolex, San Jose, California, Reliant, Takeda, AstraZeneca, and Essentialis, Carlsbad, California. Dr. Leiter received grants and speakers' honoraria from and served as a consultant and advisor for AstraZeneca, Merck & Company, Merck/Schering-Plough, and Pfizer, New York, New York. Mr. Bird, Mr. Rubino, and Drs. Lowe, Tomassini, and Tershakovec are employees of Merck & Company and may own stock and/or hold stock options in the company.