Results from a new clinical trial conducted in 1,902 patients with high cholesterol showed that Vytorin (ezetimibe/simvastatin) provided greater reduction in LDL (bad) cholesterol across the dosing ranges compared to Pfizer's Lipitor. At the most commonly used starting doses of these two therapies, Vytorin 10/20 mg decreased LDL cholesterol by 51 per cent compared with 36 per cent for Lipitor 10 mg (p<0.001), according to a Merck release.

In a subgroup of high risk patients (CHD or CHD risk equivalent), significant differences in LDL cholesterol reductions at these doses resulted in more patients achieving a goal of less than 100 mg/dL with Vytorin as compared to Lipitor; specifically, 82 per cent of high risk patients on Vytorin 10/20 mg (n=106) achieved a cholesterol lowering goal of less than 100 mg/dL as compared to only 47 per cent for patients on Lipitor 10 mg (n=106, p<0.001). High risk patients in the study with a goal of less than 100 mg/dL who were taking Vytorin 10/20 mg had a baseline LDL cholesterol of 166 mg/dL as compared to patients taking Lipitor 10 mg who had a baseline of 169 mg/dL.

Additional results from the study showed that Vytorin 10/40 mg decreased LDL cholesterol by 59 per cent compared to 48 per cent for Lipitor 40 mg in the subgroup of high risk patients. These patients had a baseline LDL cholesterol values of 169 mg/dL and 175 mg/dL respectively (p<0.001). In a post-hoc analysis of these data, significant differences in LDL cholesterol reductions, at all doses compared, resulted in more high risk patients achieving LDL cholesterol levels less than 70 mg/dL with Vytorin as compared to Lipitor. In particular, 57 per cent of high risk patients taking Vytorin 10/40 mg (n=112) achieved a LDL cholesterol goal of less than 70 mg/dL as compared with 23 percent of the patients (n=115) taking Lipitor 40 mg (p<0.001), the release says.

"In this study, Vytorin was significantly more effective than Lipitor in reducing LDL cholesterol at all doses compared and for attaining LDL cholesterol treatment goals pooled across the dosing range," Christie Ballantyne, director of the Centre for Cardiovascular Disease Prevention, Methodist DeBakey Heart Centre, Houston, Texas, and lead investigator of the study said adding, "This study gives further support to the new option that Vytorin, which reduces both the production and the absorption of cholesterol, provides to physicians in the treatment of high LDL cholesterol."

Vytorin was approved by the FDA on July 23, 2004 for the treatment of high LDL cholesterol in patients with primary hypercholesterolemia or mixed hyperlipidemia as adjunctive therapy to diet when diet alone is not enough. Vytorin is the first and only product approved to treat the two sources of cholesterol by inhibiting the production of cholesterol in the liver and blocking the absorption of cholesterol in the intestine, including cholesterol from food. The active ingredients in Vytorin are ezetimibe and simvastatin. The recommended starting dose of Vytorin is 10/20 mg (10 mg ezetimibe/20 mg simvastatin), the release added.

In other results observed in the six-week study, Vytorin 10/40 mg and 10/80 mg also provided significantly greater increases in HDL (good) cholesterol of nine per cent and eight percent respectively as compared to the HDL cholesterol increase of four percent and 1.4 per cent respectively seen in patients taking Lipitor 40 mg and 80 mg (p<0.001). Increased HDL cholesterol in patients treated with Vytorin 10/10 mg (7.7 %) and 10/20 mg (7.2 %) was numerically higher compared to Lipitor 10 mg (6.9 %) and 20 mg (5.1 %). However, these differences did not reach statistical significance.

Post-hoc analysis of C Reactive Protein (CRP) reduction showed Vytorin achieved a 25 per cent reduction, comparable to Lipitor A post-hoc analysis of archived baseline and post-baseline blood samples was performed on 1,832 of the study's enrolled patients. Results from this analysis showed that averaged across all doses, both Vytorin and Lipitor demonstrated a mean 25 per cent reduction on CRP after six weeks of treatment, Merck says.

"In addition to providing greater LDL cholesterol lowering than with Lipitor and in a pooled analysis, a greater increase in HDL, Vytorin was shown in this study to provide comparable reductions in C-Reactive Protein, "said Dr. Ballantyne. "While the exact meaning of CRP reduction is unknown, given the ongoing discussions around CRP, this is an interesting study finding. Further studies are needed to confirm these findings," Ballantyne added.

The study was a multi-centre, randomized, double-blind, active controlled parallel-group study of 1,902 patients designed to evaluate the efficacy and safety of Vytorin as compared to Lipitor across their respective dosing ranges. The primary efficacy endpoint was the percent change from baseline to the end of the 6-week treatment period in LDL cholesterol for patients treated with Vytorin or Lipitor averaged across all doses.

The results were presented at the 15th International Symposium on Drugs Affecting Lipid Metabolism (DALM), in Venice, Italy.

Merck/Schering-Plough Pharmaceuticals is a joint venture between Merck & Co, Inc. and Schering-Plough Corporation formed to develop and market in the United States new prescription medicines in cholesterol management. The collaboration was expanded to include worldwide markets (excluding Japan).