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.
RCT Entities:
BACKGROUND: Both statins and ezetimibe lower LDL-C, but ezetimibe's effect on atherosclerosis is controversial. We hypothesized that lowering LDL-Ccholesterol 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: R Corti; Z A Fayad; V Fuster; S G Worthley; G Helft; J Chesebro; M Mercuri; J J Badimon Journal: Circulation Date: 2001-07-17 Impact factor: 29.690
Authors: A T Hirsch; M H Criqui; D Treat-Jacobson; J G Regensteiner; M A Creager; J W Olin; S H Krook; D B Hunninghake; A J Comerota; M E Walsh; M M McDermott; W R Hiatt Journal: JAMA Date: 2001-09-19 Impact factor: 56.272
Authors: Claude Gagné; Harold E Bays; Stuart R Weiss; Pedro Mata; Katherine Quinto; Michael Melino; Meehyung Cho; Thomas A Musliner; Barry Gumbiner Journal: Am J Cardiol Date: 2002-11-15 Impact factor: 2.778
Authors: James A de Lemos; Michael A Blazing; Stephen D Wiviott; Eldrin F Lewis; Keith A A Fox; Harvey D White; Jean-Lucien Rouleau; Terje R Pedersen; Laura H Gardner; Robin Mukherjee; Karen E Ramsey; Joanne Palmisano; David W Bilheimer; Marc A Pfeffer; Robert M Califf; Eugene Braunwald Journal: JAMA Date: 2004-08-30 Impact factor: 56.272
Authors: Steven E Nissen; E Murat Tuzcu; Paul Schoenhagen; B Greg Brown; Peter Ganz; Robert A Vogel; Tim Crowe; Gail Howard; Christopher J Cooper; Bruce Brodie; Cindy L Grines; Anthony N DeMaria Journal: JAMA Date: 2004-03-03 Impact factor: 56.272
Authors: Barbara Nußbaumer; Anna Glechner; Angela Kaminski-Hartenthaler; Peter Mahlknecht; Gerald Gartlehner Journal: Dtsch Arztebl Int Date: 2016-07-01 Impact factor: 5.594
Authors: Amy M West; Justin D Anderson; Frederick H Epstein; Craig H Meyer; Hongkun Wang; Klaus D Hagspiel; Stuart S Berr; Nancy L Harthun; Arthur L Weltman; Joseph M Dimaria; Jennifer R Hunter; John M Christopher; Christopher M Kramer Journal: J Am Coll Cardiol Date: 2011-08-30 Impact factor: 24.094
Authors: Jamieson M Bourque; Brian J Schietinger; Jamie L Kennedy; Emily A Pearce; John M Christopher; Angela M Taylor; Coleen A McNamara; Christopher M Kramer Journal: Am J Cardiol Date: 2012-03-27 Impact factor: 2.778
Authors: Gerd Brunner; Eric Y Yang; Anirudh Kumar; Wensheng Sun; Salim S Virani; Smita I Negi; Tyler Murray; Peter H Lin; Ron C Hoogeveen; Changyi Chen; Jing-Fei Dong; Panagiotis Kougias; Addison Taylor; Alan B Lumsden; Vijay Nambi; Christie M Ballantyne; Joel D Morrisett Journal: Atherosclerosis Date: 2013-10-16 Impact factor: 5.162