title: The effect of ezetimibe on peripheral arterial atherosclerosis depends upon statin use at baseline.
abstract: BACKGROUND
  Both statins and ezetimibe lower LDL-C, but ezetimibe's effect on atherosclerosis is controversial. We hypothesized that lowering LDL-C cholesterol by adding ezetimibe to statin therapy would regress atherosclerosis measured by magnetic resonance imaging (MRI) in the superficial femoral artery (SFA) in peripheral arterial disease (PAD).
  
  
  METHODS
  Atherosclerotic plaque volume was measured in the proximal 15-20 cm of the SFA in 67 PAD patients (age 63 ± 10, ABI 0.69 ± 0.14) at baseline and annually × 2. Statin-naïve patients (n=34) were randomized to simvastatin 40 mg (S, n=16) or simvastatin 40 mg+ezetimibe 10mg (S+E, n=18). Patients already on statins but with LDL-C >80 mg/dl had open-label ezetimibe 10mg added (E, n=33). Repeated measures models estimated changes in plaque parameters over time and between-group differences.
  
  
  RESULTS
  LDL-C was lower at year 1 in S+E (67 ± 7 mg/dl) than S (91 ± 8 mg/dl, p<0.05), but similar at year 2 (68 ± 10 mg/dl vs. 83 ± 11 mg/dl, respectively). Plaque volume did not change from baseline to year 2 in either S+E (11.5 ± 1.4-10.5 ± 1.3 cm(3), p=NS) or S (11.0 ± 1.5-10.5 ± 1.4 cm(3), p=NS). In E, plaque progressed from baseline to year 2 (10.0 ± 0.8-10.8 ± 0.9, p<0.01) despite a 22% decrease in LDL-C.
  
  
  CONCLUSIONS
  Statin initiation with or without ezetimibe in statin-naïve patients halts progression of peripheral atherosclerosis. When ezetimibe is added to patients previously on statins, peripheral atherosclerosis progressed. Thus, ezetimibe's effect on peripheral atherosclerosis may depend upon relative timing of statin therapy.
authors.affiliation: Department of Medicine, University of Virginia Health System, University of Virginia, Charlottesville, VA 22908, USA.
authors.forename: Amy M
authors.initials: AM
authors.lastname: West
authors.forename: Justin D
authors.initials: JD
authors.lastname: Anderson
authors.forename: Craig H
authors.initials: CH
authors.lastname: Meyer
authors.forename: Frederick H
authors.initials: FH
authors.lastname: Epstein
authors.forename: Hongkun
authors.initials: H
authors.lastname: Wang
authors.forename: Klaus D
authors.initials: KD
authors.lastname: Hagspiel
authors.forename: Stuart S
authors.initials: SS
authors.lastname: Berr
authors.forename: Nancy L
authors.initials: NL
authors.lastname: Harthun
authors.forename: Joseph M
authors.initials: JM
authors.lastname: DiMaria
authors.forename: Jennifer R
authors.initials: JR
authors.lastname: Hunter
authors.forename: John M
authors.initials: JM
authors.lastname: Christopher
authors.forename: Joshua D
authors.initials: JD
authors.lastname: Chew
authors.forename: Gabriel B
authors.initials: GB
authors.lastname: Winberry
authors.forename: Christopher M
authors.initials: CM
authors.lastname: Kramer
mesh_terms: D000368:Aged; D000924:Anticholesteremic Agents / Q000627:therapeutic use; D050197:Atherosclerosis / Q000188:drug therapy*; D001384:Azetidines / Q000008:administration & dosage*; D008078:Cholesterol, LDL / Q000097:blood; D004311:Double-Blind Method; D000069438:Ezetimibe; D005260:Female; D005263:Femoral Artery / Q000187:drug effects; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000627:therapeutic use*; D008279:Magnetic Resonance Imaging / Q000379:methods; D008297:Male; D008875:Middle Aged; D058729:Peripheral Arterial Disease / Q000188:drug therapy*; D058226:Plaque, Atherosclerotic / Q000188:drug therapy; D011446:Prospective Studies; D019821:Simvastatin / Q000008:administration & dosage; D016896:Treatment Outcome
chemical_list: D000924:Anticholesteremic Agents; D001384:Azetidines; D008078:Cholesterol, LDL; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D019821:Simvastatin; D000069438:Ezetimibe