Ezetimibe (Zetia, Vytorin) use declining after ENHANCE trial publication in 2008

1. After the publication of the ENHANCE trial results, there was a significant decrease in the number of new initiations of ezetimibe therapy. 

2. There was also a significant increase in the number of discontinuations of ezetimibe therapy. 

Evidence Rating Level: 2 (Good) 

Study Rundown: Ezetimibe (Zetia, Vytorin) was once a very commonly prescribed drug for lowering serum low density lipoprotein (LDL) levels. However, in 2008, the New England Journal of Medicine published the ENHANCE trial, which showed that although combined therapy with ezetimibe and simvastatin decreased levels of LDL, it did not slow atherosclerosis progression as measured by intima-media thickness, as compared to simvastatin alone. Although ezetimibe sales in the six months following the study publication decreased, sales increased once again in the following years, despite the ENHANCE trial’s results being duplicated in subsequent studies.

This study sought to establish a clearer understanding of prescribing patterns for ezetimibe. The study found that following the announcement of the ENHANCE trial results in January 2008, the number of ezetimibe initiations decreased, and the number of discontinuations increased. Strengths of the study include the large number of ezetimibe users included. Limitations include that the study population was gathered from one pharmacy benefit manager, which may not be a random sample of all patients using ezetimibe. Moreover, data was gathered based on prescription filling behavior, not considering compliance. It was not possible to find the reason for individual discontinuations, and the study authors were only able to observe a trend of discontinuations and initiations.

Click to read the study in JAMA Internal Medicine

Relevant Reading:  Simvastatin with or without Ezetimibe in Familial Hypercholesterolemia

In-Depth [retrospective cohort]: This study collected deidentified data from a pharmacy benefit manager, including data from adults 18 years or older who were enrolled in that pharmacy benefit plan continuously from 2007 to 2010. Ezetimibe users included if they were prescribed either ezetimibe alone (Zetia), or ezetimibe with simvastatin (Vytorin). Users were identified if they were new initiators or those who discontinued treatment, and the month and year of that event was recorded. The impact of the ENHANCE trial was assessed using interrupted time-series regression analysis.

The study found 548,688 beneficiaries who obtained at least one prescription for an ezetimibe agent. 73.6% of those who obtained a prescription for an ezetimibe agent also obtained a prescription for another lipid-lowering agent. The announcement of the ENHANCE trial results was significantly associated with a steep decline in initiation of ezetimibe, from between 11,000-14,000 new initiations monthly to fewer than 1,500 initiations monthly. As of December 2010, there were 0.44% fewer monthly ezetimibe initiations monthly. From January to April 2008, the number of monthly ezetimibe discontinuations exceeded 16,500 (18.3%-20.6%), as compared to 3.6%-8.0% previously. As of December 2010, there were 10.4% more monthly ezetimibe discontinuations (P<0.001).

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