title: Effect of Statin Treatment on Modifying Plaque Composition: A Double-Blind, Randomized Study.
abstract: BACKGROUND
  How statins alter the natural course of coronary atherosclerosis with compositional changes remains unclear.
  
  
  OBJECTIVE
  This study aimed to determine the effect of statin therapy on modifying plaque composition.
  
  
  METHODS
  The STABLE (Statin and Atheroma Vulnerability Evaluation) prospective, single-center, double-blind, randomized study evaluated the effect of statins on functionally insignificant coronary stenoses. We randomly assigned 312 patients with a virtual histology (VH) intravascular ultrasound-defined fibroatheroma-containing index lesion to rosuvastatin 40 mg versus 10 mg (2:1 ratio). In 225 (72%) patients, grayscale- and VH-intravascular ultrasound were completed at baseline and 12 months. The primary endpoint was the change in VH-defined percent compositional volume within the target segment from baseline to follow-up in the per-protocol analysis set.
  
  
  RESULTS
  Percent necrotic core (NC) volume within the target segment significantly decreased from 21.3 ± 6.8% to 18.0 ± 7.5% during 1-year follow-up, whereas the percent fibrofatty volume increased (11.7 ± 5.8% vs. 14.8 ± 9.3%; all p < 0.001). Percent fibrous (59.4 ± 7.8% vs. 59.2 ± 8.6%) and dense calcium (7.6 ± 5.1% vs. 7.8 ± 5.6%) volumes were unchanged. Frequencies of VH (55% vs. 29%) decreased significantly. Normalized total (202.9 ± 72.3 mm(3) vs. 188.5 ± 67.8 mm(3); p = 0.001) and percent (51.4 ± 8.3% vs. 50.4 ± 8.8%; p = 0.018) atheroma volumes decreased. Independent predictors of percent NC volume change were body mass index (β = 0.37; 95% confidence interval [CI]: 0.05 to 0.70), high sensitivity C-reactive protein (β = -3.16; 95% CI: -5.64 to -0.69), and baseline percent NC volume (β = -0.44; 95% CI: -0.68 to -0.19; all p < 0.05). VH-defined percent compositional volume changes in the rosuvastatin 40- and 10-mg groups were similar.
  
  
  CONCLUSIONS
  Rosuvastatin reduced NC and plaque volume and decreased thin-cap fibroatheroma rate. There were no significant differences between high- versus moderate-intensity rosuvastatin. (Statin and Atheroma Vulnerability Evaluation [STABLE]; NCT00997880).
authors.affiliation: Department of Cardiology, University of Ulsan College of Medicine, Asan Medical Center, Seoul, South Korea. Electronic address: sjpark@amc.seoul.kr.
authors.forename: Seung-Jung
authors.initials: SJ
authors.lastname: Park
authors.affiliation: Department of Cardiology, University of Ulsan College of Medicine, Asan Medical Center, Seoul, South Korea.
authors.forename: Soo-Jin
authors.initials: SJ
authors.lastname: Kang
authors.affiliation: Department of Cardiology, University of Ulsan College of Medicine, Asan Medical Center, Seoul, South Korea.
authors.forename: Jung-Min
authors.initials: JM
authors.lastname: Ahn
authors.affiliation: Department of Cardiology, University of Ulsan College of Medicine, Asan Medical Center, Seoul, South Korea.
authors.forename: Mineok
authors.initials: M
authors.lastname: Chang
authors.affiliation: Department of Biostatistics, University of Ulsan College of Medicine, Asan Medical Center, Seoul, South Korea.
authors.forename: Sung-Cheol
authors.initials: SC
authors.lastname: Yun
authors.affiliation: Department of Cardiology, University of Ulsan College of Medicine, Asan Medical Center, Seoul, South Korea.
authors.forename: Jae Hyung
authors.initials: JH
authors.lastname: Roh
authors.affiliation: Department of Cardiology, University of Ulsan College of Medicine, Asan Medical Center, Seoul, South Korea.
authors.forename: Pil Hyung
authors.initials: PH
authors.lastname: Lee
authors.affiliation: Department of Cardiology, University of Ulsan College of Medicine, Asan Medical Center, Seoul, South Korea.
authors.forename: Hyun Woo
authors.initials: HW
authors.lastname: Park
authors.affiliation: Department of Cardiology, University of Ulsan College of Medicine, Asan Medical Center, Seoul, South Korea.
authors.forename: Sung-Han
authors.initials: SH
authors.lastname: Yoon
authors.affiliation: Department of Cardiology, University of Ulsan College of Medicine, Asan Medical Center, Seoul, South Korea.
authors.forename: Duk-Woo
authors.initials: DW
authors.lastname: Park
authors.affiliation: Department of Cardiology, University of Ulsan College of Medicine, Asan Medical Center, Seoul, South Korea.
authors.forename: Seung-Whan
authors.initials: SW
authors.lastname: Lee
authors.affiliation: Department of Cardiology, University of Ulsan College of Medicine, Asan Medical Center, Seoul, South Korea.
authors.forename: Young-Hak
authors.initials: YH
authors.lastname: Kim
authors.affiliation: Department of Cardiology, University of Ulsan College of Medicine, Asan Medical Center, Seoul, South Korea.
authors.forename: Cheol Whan
authors.initials: CW
authors.lastname: Lee
authors.affiliation: Cardiovascular Research Foundation, New York, New York.
authors.forename: Gary S
authors.initials: GS
authors.lastname: Mintz
authors.affiliation: Department of Cardiology, University of Ulsan College of Medicine, Asan Medical Center, Seoul, South Korea.
authors.forename: Ki Hoon
authors.initials: KH
authors.lastname: Han
authors.affiliation: Department of Cardiology, University of Ulsan College of Medicine, Asan Medical Center, Seoul, South Korea.
authors.forename: Seong-Wook
authors.initials: SW
authors.lastname: Park
mesh_terms: D003324:Coronary Artery Disease / Q000175:diagnosis / Q000188:drug therapy; D003331:Coronary Vessels / Q000000981:diagnostic imaging / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D016903:Drug Monitoring / Q000379:methods; D005260:Female; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000008:administration & dosage; D008297:Male; D008875:Middle Aged; D058226:Plaque, Atherosclerotic / Q000188:drug therapy / Q000473:pathology; D011379:Prognosis; D000068718:Rosuvastatin Calcium / Q000008:administration & dosage*; D016896:Treatment Outcome; D018084:Ultrasonography, Interventional / Q000379:methods
chemical_list: D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D000068718:Rosuvastatin Calcium
keywords: atherosclerosis; hydroxymethylglutaryl-CoA reductase inhibitors; intravascular ultrasound