title: Changing characteristics of statin-related cIMT trials from 1988 to 2006.
abstract: OBJECTIVE
  Changes in cIMT have not been consistently correlated with cardiovascular risk reduction in clinical studies. The variability of carotid intima media thickness (cIMT) changes in published statin LDL-C-lowering studies in relation to various baseline and study characteristics was assessed.
  
  
  METHODS
  This was an exploratory analysis of study-level data pooled from statin-treatment arms of 13 studies conducted during 1988-2006. Baseline mean common carotid artery (CCA)/cIMT, maximum mean CCA/cIMT and LDL-C levels, and annualized cIMT changes were estimated for the overall studies, those conducted before/after 2000, and in risk-based subgroups. Potential relationships between prespecified covariates and cIMT changes were assessed.
  
  
  RESULTS
  Baseline mean CCA/cIMT and LDL-C levels were higher in the combined studies conducted before year 2000 (0.8521 mm) than after 2000 (0.7458 mm), and somewhat higher in study populations of patients with coronary heart disease risk and those with greater LDL-C reductions. Mean CCA/cIMT changes were also larger for the studies conducted before 2000 (-0.0119 mm/year) than after 2000 (-0.0013 mm/year). Notably, studies conducted before 2000 were of longer duration (≥ 2 years) than after 2000 (<2 years). Heterogeneity in cIMT change was attributed to baseline and study-design characteristics. Longer study duration and greater LDL-C reductions were significantly related to larger annualized cIMT changes. Maximum cIMT results were similar.
  
  
  CONCLUSIONS
  Baseline cIMT and LDL-C levels were lower, and cIMT changes were smaller in statin cIMT trials conducted after 2000 than those before 2000. These trends are consistent with increased treatment and control of high LDL-C levels over recent years in clinical practice, and may influence the results of cIMT studies.
authors.affiliation: Preventive Cardiology, The University of Chicago Pritzker School of Medicine, 515 North State Street Suite 2700, Chicago, IL 60610, USA. Electronic address: mdavidso@bsd.uchicago.edu.
authors.forename: Michael H
authors.initials: MH
authors.lastname: Davidson
authors.affiliation: Global Clinical Development, Merck & Co., Inc., 2000 Galloping Hill Road, Kenilworth, NJ 07033, USA. Electronic address: joanne_tomassini@merck.com.
authors.forename: Joanne E
authors.initials: JE
authors.lastname: Tomassini
authors.affiliation: Global Clinical Development, Merck & Co., Inc., 2000 Galloping Hill Road, Kenilworth, NJ 07033, USA. Electronic address: EHJ1234@comcast.net.
authors.forename: Erin
authors.initials: E
authors.lastname: Jensen
authors.affiliation: Global Clinical Development, Merck & Co., Inc., 2000 Galloping Hill Road, Kenilworth, NJ 07033, USA. Electronic address: drneffdo@hotmail.com.
authors.forename: David
authors.initials: D
authors.lastname: Neff
authors.affiliation: Global Clinical Development, Merck & Co., Inc., 2000 Galloping Hill Road, Kenilworth, NJ 07033, USA. Electronic address: adam_polis@merck.com.
authors.forename: Adam B
authors.initials: AB
authors.lastname: Polis
authors.affiliation: Global Clinical Development, Merck & Co., Inc., 2000 Galloping Hill Road, Kenilworth, NJ 07033, USA. Electronic address: andrew_tershakovec@merck.com.
authors.forename: Andrew M
authors.initials: AM
authors.lastname: Tershakovec
mesh_terms: D015415:Biomarkers / Q000097:blood; D002340:Carotid Artery Diseases / Q000000981:diagnostic imaging / Q000209:etiology / Q000517:prevention & control*; D017536:Carotid Artery, Common / Q000000981:diagnostic imaging / Q000187:drug effects*; D059168:Carotid Intima-Media Thickness; D008078:Cholesterol, LDL / Q000097:blood; D002986:Clinical Trials as Topic; D018450:Disease Progression; D050171:Dyslipidemias / Q000097:blood / Q000150:complications / Q000175:diagnosis / Q000188:drug therapy*; D005260:Female; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D011237:Predictive Value of Tests; D012307:Risk Factors; D013997:Time Factors; D016896:Treatment Outcome
chemical_list: D015415:Biomarkers; D008078:Cholesterol, LDL; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors
keywords: Carotid intima media thickness; LDL-C; Statin; Variability