Results from a new prespecified analysis of the VYVA ( VYtorin Versus Atorvastatin ) trial involving a subgroup of 428 patients with type 2 diabetes were consistent with the overall VYVA trial.

In this new analysis, results showed that Vytorin ( Ezetimibe/Simvastatin ), provided 56% reduction in LDL cholesterol across the dosing range in these patients as compared to 46% reduction seen in patients taking Atorvastatin ( Lipitor ) [ treatment Difference 10.6% ].

At the most commonly used starting doses, 59 diabetic patients taking Vytorin 10/20 mg, reduced their LDL cholesterol by 53% as compared to the 35% reduction seen in the 46 patients taking Lipitor 10 mg. This difference was similar to the results seen in the overall study population.

" The results seen in this new analysis, in patients with type 2 diabetes, showed that Vytorin was more effective than Lipitor in reducing LDL cholesterol at all doses compared, including the most commonly used starting doses," said Christie Ballantyne, at the Methodist DeBakey Heart Center, Houston, and lead investigator of the study.

Vytorin is indicated 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 incremental benefit of Vytorin on cardiovascular morbidity and mortality over and above that demonstrated by Simvastatin has not been established.

Vytorin should not be taken by people who are hypersensitive to any of its components. Vytorin should not be taken by anyone with active liver disease or unexplained persistent elevations of serum transaminases. Women who are of childbearing age ( unless highly unlikely to conceive ), are nursing or who are pregnant should not take Vytorin.

Results of the overall VYVA trial demonstrated that Vytorin was superior to Lipitor in lowering LDL cholesterol.

The VYVA study was a multicenter, 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 study enrolled men and women 18 to 79 years of age with an LDL cholesterol level at or above drug treatment thresholds established by the NCEP ATP III who were deemed eligible if they met the following criteria: established coronary heart disease ( CHD ) or CHD risk equivalent, or two or more risk factors conferring a 10-year risk for CHD greater than 20% ( by Framingham score ) with an LDL cholesterol greater than or equal to 130 mg/dL; no established CHD or CHD risk equivalent, with two or more risk factors conferring a 10-year risk for CHD greater than or equal to 10% and less than or equal to 20% with an LDL cholesterol greater than or equal to 130 mg/dL; no established CHD or CHD risk equivalent, with two or more risk factors conferring a 10-year risk for CHD less than 10% with an LDL cholesterol greater than or equal to 160 mg/dL; and no established CHD or CHD risk equivalent, with less than two risk factors, and with LDL cholesterol greater than or equal to 190 mg/dL.
Other criteria included fasting serum triglyceride ( TG ) level less than or equal to 350 mg/dL, alanine aminotransferase ( ALT ), aspartate aminotransferase ( AST ), or creatine kinase ( CK ) level less than or equal to 1.5 times the upper limit of normal, serum creatinine level less than or equal to 1.5 mg/dL, and a hemoglobin A1C less than nine% in patients with diabetes.

Important cautionary information for Vytorin

Muscle pain, tenderness or weakness in people taking Vytorin should be reported to a doctor promptly because these could be signs of a serious side effect. Vytorin should be discontinued if myopathy is diagnosed or suspected. To help avoid serious side effects, patients should talk to their doctor about medicine or food they should avoid while taking Vytorin.

In three placebo-controlled, 12-week trials, the incidence of consecutive elevations ( >/=3 X ULN ) in serum transaminases were 1.7% overall for patients treated with Vytorin and 2.6% for patients treated with Vytorin 10/80 mg. In controlled long-term ( 48 week ) extensions, which included both newly treated and previously treated patients, the incidence of consecutive elevations ( >/=3 X ULN ) in serum transaminases was 1.8% overall and 3.6% for patients treated with Vytorin 10/80 mg.
These elevations in transaminases were generally asymptomatic, not associated with cholestasis and returned to baseline after discontinuation of therapy or with continued treatment.
Doctors should perform blood tests before, and periodically during treatment with Vytorin when clinically indicated to check for liver problems.
People taking Vytorin 10/80 mg should receive an additional liver function test prior to and three months after titration and periodically during the first year.
Due to the unknown effects of increased exposure to Ezetimibe ( an ingredient in Vytorin ) in patients with moderate or severe hepatic insufficiency, Vytorin is not recommended in these patients.

The safety and effectiveness of Vytorin with fibrates have not been established; therefore, co-administration with fibrates is not recommended.

Caution should be exercised when initiating Vytorin in patients treated with cyclosporine and in patients with severe renal insufficiency.

In clinical studies Vytorin was well tolerated with a low incidence of adverse events
Vytorin has been evaluated for safety in more than 3,800 patients in clinical trials and was generally well tolerated at all doses ( 10/10 mg, 10/20 mg, 10/40 mg, 10/80 mg ).
In clinical trials, the most commonly reported side effects, regardless of cause, included headache ( 6.8% ), upper respiratory tract infection ( 3.9% ), myalgia ( 3.5% ), influenza ( 2.6% ) and extremity pain ( 2.3% ).

Source: Merck, 2005


XagenaMedicine2005