The effect of ezetimibe on peripheral arterial atherosclerosis depends upon statin use at baseline

Amy M. West, Justin D. Anderson, Craig H. Meyer, Frederick H. Epstein, Hongkun Wang, Klaus D. Hagspiel, Stuart S. Berr, Nancy L. Harthun, Joseph M. DiMaria, Jennifer R. Hunter, John M. Christopher, Joshua D. Chew, Gabriel B. Winberry, Christopher M. Kramer

Research output: Contribution to journalArticlepeer-review

49 Scopus citations


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 10 mg (S + E, n=18). Patients already on statins but with LDL-C >80. mg/dl had open-label ezetimibe 10. mg 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±7mg/dl) than S (91±8mg/dl, p<0.05), but similar at year 2 (68±10mg/dl vs. 83±11mg/dl, respectively). Plaque volume did not change from baseline to year 2 in either S+E (11.5±1.4-10.5±1.3cm 3, p=NS) or S (11.0±1.5-10.5±1.4cm 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. Clinical Trial Registration Information - NCT00587678

Original languageEnglish (US)
Pages (from-to)156-162
Number of pages7
Issue number1
StatePublished - Sep 2011


  • Atherosclerosis
  • Lipids
  • Magnetic resonance imaging
  • Peripheral vascular disease
  • Plaque

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine


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