Ezetimibe, and the combination of ezetimibe/simvastatin, and risk of cancer: A post-marketing analysis

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 simivastatin, 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. (c) 2009 National Lipid Association. All rights reserved.