A review of data from three studies indicates that simvastatin, ezetimibe, or the combination of the two are not likely to be increase the risk of cancer or death from cancer, but that the association cannot be “definitively ruled out,” the Food and Drug Administration announced.
The FDA announcement is a follow-up to an announcement made by the agency in August 2008 about a safety review of these products, based on the preliminary results of the Simvasatatin and Ezetimibe in Aortic Stenosis (SEAS) trial of 1,873 patents with aortic stenosis, which found a higher rate of cancer (11.1%) among those on Vytorin 10/40 (10 mg of ezetimibe and 40 mg of simvastatin), compared with those on placebo (7.5%). The number of cancer-related deaths was also higher among those on Vytorin in this study. Vytorin is a combination of simvastatin (Zocor) and ezetimibe (Zetia).
The FDA has finished a review of data from SEAS, which is completed, and interim data from two large ongoing studies with lower doses of Vytorin, the SHARP (Study of Heart and Renal Protection) and IMPROVE-IT (Improved Reduction of Outcomes: Vytorin Efficacy International Trial).
“Based on the currently available information, FDA believes it is unlikely that Vytorin or Zetia increase the risk of cancer or cancer-related death, but at this time an association cannot be definitively ruled out,” the statement said. “FDA is not advising healthcare professionals or consumers to stop using these medications, but to continue to evaluate the clinical benefits and potential risks of Vytorin or Zetia compared to other FDA-approved cholesterol lowering medications.”
The SHARP study compares Vytorin (10/20 mg) to placebo, to determine whether reducing cholesterol with the combination product can prevent heart disease and strokes in patients with kidney disease.
IMPROVE-IT is comparing the clinical benefit (the reduction in the risk of the composite end point of cardiovascular death, major coronary events, and stroke) of Vytorin (10/40 mg) to 40 mg of simvastatin, in high-risk subjects with stabilized high-risk acute coronary syndrome.
An interim analysis of a total of 20,617 patients from these two studies found no increased risk of cancer associated with Vytorin. There were 97 cancer-related deaths, however, compared with 72 deaths among those in the control groups, but the difference was not statistically significant.
The cancer risk associated with Vytorin will be evaluated further when these studies are completed in 2010 (SHARP) and 2012 (IMPROVE-IT), according to the FDA.
Other factors that the agency considered in its review included animal studies that did not find an association between ezetimibe and an increased incidence of cancer.
In addition, there was not a consistent increase in the risk of cancer over time in the SEAS study, which would be expected if the drug caused cancer or promoted the growth of preexisting cancers, and the increase in cancer and cancer deaths in the study was due to combining a variety of cancer types, according to the statement.
The notice can be found at www.fda.gov/Drugs/DrugSafety/PostmarketDrugSafetyInformationforPatientsandProviders/DrugSafetyInformationforHeathcareProfessionals/ucm194964.htmwww.fda.gov/medwatch