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.

Trial registration: ClinicalTrials.gov NCT00587678.

Conflict of interest statement

COMPETING INTEREST

Drs. Epstein, Meyer, Hagspiel, and Kramer receive research support from Siemens Medical Solutions. All other authors have no declared conflicts of interest.

Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

Figures

Figure 1

Patient flow diagram through the study.

Figure 2

Representative black blood turbo spin echo MRI of one 3mm slice of the superficial femoral artery (arrow) in a S+E patient (top) at baseline (A) and year two (B) demonstrating lack of change over time and an E patient (bottom) at baseline (C) and year two (D) demonstrating subtle plaque progression. Note the excellent match between imaging locations at the different time points.

Figure 3

Graph comparing change in plaque volume over time for each of the study groups (S= simvastatin only, S+E = simvastatin plus ezetimibe and E = open label ezetimibe added to ongoing statin use at baseline). *p