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

Abstract

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 PARTICIPANTSRetrospective 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 MEASURESLipid-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 RELEVANCEAfter 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.

Ezetimibe: Use, costs, and adverse events in Australia

“…The trends in the use and costs of ezetimibe are similar to those reported for the United States, Canada, and Europe. 7,13,17 In contrast to some other studies, 18,19 we did not see any obvious reduction in ezetimibe use after the ENHANCE trial was published in 2008. 8 That trial showed that ezetimibe plus simvastatin, compared to simvastatin alone, had no effect on intima-media thickness in atherosclerosis in patients with familial hypercholesterolemia.…”

Current Treatment of Dyslipidemia: Evolving Roles of Non-Statin and Newer Drugs

“…Later analysis showed that ezetimibe use was indeed related to variability in formulary restrictiveness [172]. Through 2007-2010, 29.1 % of continuously eligible adults obtained at least one lipid-lowering medication [173]. Among them, 17.8 % were given ezetimibe and 95.3 % another agent, usually statins.…”

Improving the odds: ezetimibe and cardiovascular disease

“…Critics rightly started questioning the validity of using ezetimibe based on its ability to lower LDL‐C. Previous sales of ezetimibe which had been high based on its lipid‐lowering efficacy and convenience then fell . Later the results of the torcetrapib outcomes trial again with a drug efficacious at lowering LDL‐C were also adverse but followed negative cIMT surrogate outcomes trials .…”