Impact of the ENHANCE Trial on the use of ezetimibe in the United States and Canada

Background We previously found that the use of ezetimibe increased rapidly with different patterns between the United States (US) and Canada prior to the landmark Ezetimibe and Simvastatin in Hypercholesterolemia Enhance Atherosclerosis Regression (ENHANCE) trial, which was reported in January 2008, and failed to show that the drug slowed the progression of atherosclerosis. What is not known is how practice in the 2 countries changed after the ENHANCE trial. We examined ezetimibe use trends in the US and Canada before and after the reporting of the ENHANCE trial. Methods We conducted a population-based, retrospective, time-series analysis using the data collected by IMS Health in the US and CompuScript in Canada from January 1, 2002, to December 31, 2009. The main outcome measure was monthly number of prescriptions for ezetimibe-containing products. Results The monthly number of ezetimibe prescriptions/100,000 population rose from 6 to 1,082 in the US from November 2002 to January 2008, then significantly declined to 572/100,000 population by December 2009 after the release of the ENHANCE trial, a decrease of 47.1% (P < .001). In contrast, in Canada, use continuously rose from 2 to 495/100,000 population from June 2003 to December 2009 (P = .2). United States expenditures totaled $2.24 billion in 2009. Conclusions Ezetimibe remains commonly used in both the US and Canada. Ezetimibe use has decreased in the US post-ENHANCE, whereas use has gradually but steadily increased in Canada. The diverging patterns of ezetimibe use in the US and Canada require further investigation, as they reveal that a common evidence base is eliciting very different utilization patterns in neighboring countries.