TY - JOUR
T1 - The effect of ezetimibe on peripheral arterial atherosclerosis depends upon statin use at baseline
AU - West, Amy M.
AU - Anderson, Justin D.
AU - Meyer, Craig H.
AU - Epstein, Frederick H.
AU - Wang, Hongkun
AU - Hagspiel, Klaus D.
AU - Berr, Stuart S.
AU - Harthun, Nancy L.
AU - DiMaria, Joseph M.
AU - Hunter, Jennifer R.
AU - Christopher, John M.
AU - Chew, Joshua D.
AU - Winberry, Gabriel B.
AU - Kramer, Christopher M.
N1 - Funding Information:
This work was supported by the National Heart Lung and Blood Institute at the National Institutes of Health, grant number: R01 HL075792 (CMK) and the National Center for Research Resources , grant number: M01RR000847 and the National Institute of Biomedical Imaging and Bioengineering , grant number: T32 EB003841 (JDA, AMW). Study drugs were supplied by Merck Schering Plough.
PY - 2011/9
Y1 - 2011/9
N2 - 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 http://clinicaltrials.gov/ct2/show/NCT00587678.
AB - 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 http://clinicaltrials.gov/ct2/show/NCT00587678.
KW - Atherosclerosis
KW - Lipids
KW - Magnetic resonance imaging
KW - Peripheral vascular disease
KW - Plaque
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U2 - 10.1016/j.atherosclerosis.2011.04.005
DO - 10.1016/j.atherosclerosis.2011.04.005
M3 - Article
C2 - 21570685
AN - SCOPUS:80052094401
SN - 0021-9150
VL - 218
SP - 156
EP - 162
JO - Atherosclerosis
JF - Atherosclerosis
IS - 1
ER -