Trends in Use of Ezetimibe After the ENHANCE Trial, 2007 Through 2010

JAMA Intern Med. 2014 Sep;174(9):1486-93. doi: 10.1001/jamainternmed.2014.3404.


Importance: Results from the Ezetimibe and Simvastatin in Hypercholesterolemia Enhances Atherosclerosis Regression (ENHANCE) trial, announced in January 2008, demonstrated that ezetimibe use lowered cholesterol levels but did not slow the progression of atherosclerosis.

Objective: To examine the association of this announcement with national patterns of ezetimibe prescribing, including medication initiation and discontinuation, as well as predictors of use.

Design, setting, and participants: Retrospective analysis of a national sample of adults 18 years or older who were continuously enrolled in plans of a large US pharmacy benefit manager from 2007 to 2010.

Main outcomes and measures: Lipid-lowering therapy prescription claims were categorized as ezetimibe-containing treatments or any other lipid-lowering agent. Initiation was defined as an ezetimibe claim without another in the prior 180 days; discontinuation, as an ezetimibe claim without another in the subsequent 180 days.

Results: From 2007 to 2010, 29.1% of the 10,597,296 continuously eligible adults obtained at least 1 lipid-lowering agent prescription. Among these adults, 17.8% were prescribed ezetimibe and 95.3% another lipid-lowering agent, predominantly statins. Ezetimibe use peaked in January 2008, when 2.5% of all adults were ezetimibe users, but declined to 1.8% by December 2010. The ENHANCE trial announcement was associated with a nonsignificant 0.16% fewer monthly ezetimibe users (P = .11) but a significant 0.14% more monthly monotherapy users and 0.30% fewer users of ezetimibe concomitant with other lipid-lowering agents (both P = .01). The ENHANCE trial was also associated with 0.44% fewer monthly ezetimibe initiations (P = .002) and 10.4% more monthly ezetimibe discontinuations (P < .001), particularly of ezetimibe monotherapy for both. More than half of adults who initiated ezetimibe use did so without first being prescribed another lipid-lowering agent, both before (50%-60%) and after (60%-70%) the trial. Those aged 50 to 64 years and those living in the East South Central US Census division were both more likely to initiate and less likely to discontinue ezetimibe after the ENHANCE trial.

Conclusions and relevance: After announcement of the results of the ENHANCE trial, nearly 2% of all continuously enrolled adult beneficiaries within a large US pharmacy benefit manager used ezetimibe, although ezetimibe initiations declined and discontinuations increased.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Anticholesteremic Agents / therapeutic use*
  • Atherosclerosis / prevention & control
  • Azetidines / therapeutic use*
  • Clinical Trials as Topic
  • Disease Progression
  • Ezetimibe
  • Female
  • Humans
  • Hypercholesterolemia / drug therapy*
  • Insurance, Pharmaceutical Services
  • Male
  • Middle Aged
  • Retrospective Studies
  • Simvastatin / therapeutic use
  • Treatment Outcome
  • United States


  • Anticholesteremic Agents
  • Azetidines
  • Simvastatin
  • Ezetimibe