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 15–20cm of the SFA in 67 PAD patients (age 63±10, ABI 0.69±0.14) at baseline and annually×2. Statin-naive patients ( n =34) were randomized to simvastatin 40mg (S, n =16) or simvastatin 40mg+ezetimibe 10mg (S+E, n =18). Patients already on statins but with LDL-C >80mg/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±7mg/dl) than S (91±8mg/dl, p 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 Conclusions Statin initiation with or without ezetimibe in statin-naive 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 http://clinicaltrials.gov/ct2/show/NCT00587678.