title: Effect of ezetimibe on major atherosclerotic disease events and all-cause mortality.
abstract: Despite ezetimibe's ability to reduce serum cholesterol levels, there are concerns over its vascular effects and whether it prevents or ameliorates atherosclerotic disease (AD). The aims of this study were to estimate the effect of ezetimibe use on major AD events and all-cause mortality and to compare these associations to those observed for hydroxymethylglutaryl coenzyme A reductase inhibitor (statin) use. A total of 367 new ezetimibe users were identified from November 1, 2002, to December 31, 2009. These subjects were aged ≥18 years and had no previous statin use. One to 4 statin user matches were identified for each ezetimibe user, resulting in a total of 1,238 closely matched statin users. Pharmacy data and drug dosage information were used to estimate a moving window of ezetimibe and statin exposure for each day of study follow-up. The primary outcome was a composite of major AD events (coronary heart disease, cerebrovascular disease, and peripheral vascular disease events) and all-cause death. Ezetimibe use (odds ratio 0.33, 95% confidence interval 0.13 to 0.86) and statin use (odds ratio 0.61, 95% confidence interval 0.36 to 1.04) were associated with reductions in the likelihood of the composite outcome. These protective associations were most significant for cerebrovascular disease events and all-cause death. Subgroup analyses by gender, race or ethnicity, history of AD, diabetes status, and estimated renal function showed consistent estimates across strata, with no significant differences between ezetimibe and statin use. In conclusion, ezetimibe appeared to have a protective effect on major AD events and all-cause death that was not significantly different from that observed for statin use.
authors.affiliation: Department of Internal Medicine, Henry Ford Health System, Detroit, Michigan, USA.
authors.forename: Sami
authors.initials: S
authors.lastname: Hayek
authors.forename: Fabrizio
authors.initials: F
authors.lastname: Canepa Escaro
authors.forename: Assad
authors.initials: A
authors.lastname: Sattar
authors.forename: Steven
authors.initials: S
authors.lastname: Gamalski
authors.forename: Karen E
authors.initials: KE
authors.lastname: Wells
authors.forename: George
authors.initials: G
authors.lastname: Divine
authors.forename: Brian K
authors.initials: BK
authors.lastname: Ahmedani
authors.forename: David E
authors.initials: DE
authors.lastname: Lanfear
authors.forename: Manel
authors.initials: M
authors.lastname: Pladevall
authors.forename: L Keoki
authors.initials: LK
authors.lastname: Williams
mesh_terms: D000924:Anticholesteremic Agents / Q000008:administration & dosage; D050197:Atherosclerosis / Q000097:blood / Q000188:drug therapy* / Q000401:mortality; D001384:Azetidines / Q000008:administration & dosage*; D002423:Cause of Death / Q000639:trends; D008078:Cholesterol, LDL / Q000097:blood / Q000187:drug effects; D003324:Coronary Artery Disease / Q000097:blood / Q000188:drug therapy / Q000401:mortality*; D000069438:Ezetimibe; D005260:Female; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000008:administration & dosage; D008297:Male; D008824:Michigan / Q000453:epidemiology; D008875:Middle Aged; D016017:Odds Ratio; D012189:Retrospective Studies
chemical_list: D000924:Anticholesteremic Agents; D001384:Azetidines; D008078:Cholesterol, LDL; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D000069438:Ezetimibe