title: Integrated Biomarker and Imaging Study 3 (IBIS-3) to assess the ability of rosuvastatin to decrease necrotic core in coronary arteries.
abstract: OBJECTIVE
  Statins are highly effective in reducing major adverse clinical events, but the direct effects on coronary plaque composition remain debatable. Our aim was to mechanistically evaluate the treatment effect of high-intensity statin therapy on compositional coronary plaque changes.
  
  
  RESULTS
  The third Integrated Biomarker and Imaging Study (IBIS-3) was a prospective, investigator-initiated, single-centre study. Serial radiofrequency intravascular ultrasound (RF-IVUS) measurements of a predefined non-stenotic segment in a non-culprit coronary artery were performed to evaluate the effect of rosuvastatin (intended dose: 40 mg daily) on necrotic core (NC) volume in patients with stable angina or acute coronary syndrome. Changes in lipid core burden index (LCBI) were evaluated through serial near-infrared spectroscopy (NIRS) imaging in a subset. Serial RF-IVUS (and NIRS) data of a median segment of 41 mm (interquartile range: 32 to 49 mm) were complete in 164 (103) patients. Follow-up measurements were performed at six and 12 months in 30 (26) and 134 (77) patients, respectively. Mean levels of low-density lipoprotein cholesterol decreased by 30%, from 2.49 mmol/l to 1.73 mmol/l at the end of follow-up. High-dose rosuvastatin therapy resulted in a non-significant change of -1.4 mm3 (95% CI: -3.0, 0.1) in NC volume during follow-up (p=0.074). The change in NC percentage of total plaque volume was -1.4% (95% CI: -2.4 to -0.4; p=0.006). A neutral effect was also observed on LCBI. Indications of significant regression of NC volume and LCBI in the highest baseline quartiles were observed, which should cautiously be regarded as hypothesis-generating.
  
  
  CONCLUSIONS
  High-intensity rosuvastatin therapy during one year resulted in a neutral effect on NC and LCBI within non-stenotic, non-culprit coronary segments with a relatively low atheroma burden. This study has been registered in The Netherlands Trial Register (NTR) nr. 2872.
authors.affiliation: Thoraxcenter, Department of Cardiology, Erasmus MC and Cardiovascular Research Institute (COEUR), Rotterdam, The Netherlands.
authors.forename: Rohit M
authors.initials: RM
authors.lastname: Oemrawsingh
authors.forename: Hector M
authors.initials: HM
authors.lastname: Garcia-Garcia
authors.forename: Robert J M
authors.initials: RJ
authors.lastname: van Geuns
authors.forename: Mattie J
authors.initials: MJ
authors.lastname: Lenzen
authors.forename: Cihan
authors.initials: C
authors.lastname: Simsek
authors.forename: Sanneke P M
authors.initials: SP
authors.lastname: de Boer
authors.forename: Nicolas M
authors.initials: NM
authors.lastname: Van Mieghem
authors.forename: Evelyn
authors.initials: E
authors.lastname: Regar
authors.forename: Peter P T
authors.initials: PP
authors.lastname: de Jaegere
authors.forename: K Martijn
authors.initials: KM
authors.lastname: Akkerhuis
authors.forename: Jurgen M R
authors.initials: JM
authors.lastname: Ligthart
authors.forename: Felix
authors.initials: F
authors.lastname: Zijlstra
authors.forename: Patrick W
authors.initials: PW
authors.lastname: Serruys
authors.forename: Eric
authors.initials: E
authors.lastname: Boersma
mesh_terms: D000368:Aged; D015415:Biomarkers / Q000097:blood; D003324:Coronary Artery Disease / Q000097:blood / Q000000981:diagnostic imaging / Q000188:drug therapy*; D003331:Coronary Vessels / Q000000981:diagnostic imaging / Q000187:drug effects*; D005260:Female; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000494:pharmacology / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D000068718:Rosuvastatin Calcium / Q000494:pharmacology / Q000627:therapeutic use*; D019265:Spectroscopy, Near-Infrared; D018084:Ultrasonography, Interventional
chemical_list: D015415:Biomarkers; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D000068718:Rosuvastatin Calcium