Ezetimibe, and the combination of ezetimibe/simvastatin, and risk of cancer: A post-marketing analysis
Received 13 November 2008; accepted 8 February 2009. published online 12 February 2009.
Background
In the recently reported Simvastatin and Ezetimibe in Aortic Stenosis (SEAS) trial, the combination of ezetimibe/simvastatin (E/S) was associated with a significantly increased risk of cancer compared to placebo, causing widespread public concern.
Objective
We examined the rates of cancer adverse event reports filed with the US Food and Drug Administration (FDA) of patients on ezetimibe or E/S, and compared these to reports with other potent cholesterol-lowering drugs.
Methods
We tabulated all adverse event reports listing “cancer” or “malignancy” filed with the FDA (July 2004 to March 2008) of patients taking ezetimibe or E/S, and compared those to reports of patients taking simvastatin, atorvastatin, or rosuvastatin. We calculated rates for such reports per million prescriptions. A secondary analysis examined cancer reports as a proportion of all reported adverse events for each medication.
Results
Prescriptions for all drugs totaled 559 million (approximately 52 and 55 million prescriptions of ezetimibe and E/S, respectively), and cancer adverse event reports totaled 2334. There were 2.9 and 1.3 cancer-associated adverse event reports per million ezetimibe or E/S prescriptions, respectively, compared to a range of 3.1 to 5.1 per million prescriptions for the other drugs. Findings were similar when only reports listing the drug as “suspect” were considered. The proportions of reports listing cancer relative to all adverse event reports were 2.0% and 1.9% for ezetimibe and E/S, respectively, compared to a range of 1.3% to 3.9% for the other drugs.
Conclusions
This large-scale post-marketing analysis of reported adverse events does not support that ezetimibe or E/S increase the risk of cancer.
aInstitute for Clinical Research and Health Policy Studies, Tufts Medical Center and Tufts University School of Medicine, 800 Washington St, Box #80, Boston, MA 02111USA
bMolecular Cardiology Research Institute, Department of Medicine, Tufts Medical Center and Tufts University School of Medicine, 800 Washington St, Boston, MA 02111USA
ABSTRACT