The FDA ( Food and Drug Administration ) is investigating a report from the SEAS trial ( Simvastatin and Ezetimibe in Aortic Stenosis ) of a possible association between the use of Vytorin ( a combination of Simvastatin plus Ezetimibe ) and a potentially increased incidence of cancer.
Simvastatin ( Zocor ), a statin approved in 1991, decreases production of cholesterol by the liver and is indicated to reduce LDL-cholesterol levels and reduce the risk of cardiovascular events such as heart attack and stroke.
Ezetimibe ( Zetia ), approved in 2002, inhibits the absorption of cholesterol in the intestine and is indicated to reduce LDL-cholesterol levels.
Vytorin, the combination product approved in 2004, is indicated to reduce LDL-cholesterol levels.
Recently, FDA obtained preliminary results from the SEAS trial. This clinical trial tested whether lowering LDL-cholesterol with Vytorin would reduce the risk of major cardiovascular events, including aortic valve replacement, congestive heart failure, and ischemic cardiovascular events in individuals with aortic stenosis.
A lower overall cardiovascular risk was not found with Vytorin. However, there was an additional observation that a larger percentage of subjects treated with Vytorin were diagnosed with and died from all types of cancer combined ( including skin cancer ) when compared to placebo during the 5-year study.
Interim data from two large ongoing cardiovascular trials of Vytorin – the Study of Heart and Renal Protection ( SHARP ) and the Improved Reduction in High-Risk Subjects Presenting with Acute Coronary Syndrome ( IMPROVE-IT ) – show no increased risk of cancer with the combination of Simvastatin plus Ezetimibe.
The SHARP trial is expected to be completed in 2010. The IMPROVE-IT trial is scheduled for completion around 2012.
Safety data from both of these trials are being evaluated on a regular basis by independent data safety monitoring boards.
FDA has determined that, to date, these findings in the SEAS trial plus the interim data from ongoing trials should not prompt patients to stop taking Vytorin or any other cholesterol lowering drug.
FDA is aware of previous reports suggesting a link between low on-treatment cholesterol levels and an increased risk of cancer.
A 2007 pooled analysis of 16 studies with 23 statin drug arms, published in the Journal of the American College of Cardiology, reported an association between the level of LDL-cholesterol achieved and incident cancer in patients receiving a statin.
However, most large prospective studies of statin drugs have reported no difference in cancer incidence between the active and placebo arms. For Simvastatin, the Heart Protection Study randomized 20,000 patients to a daily dose of Simvastatin 40 mg or placebo for up to 5 years.
The incidence rate for cancer was 7.9% in the simvastatin group and 7.8% in the placebo group, and the deaths from cancer occurred at similar rates in both groups.
Source: FDA, 2008
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