Intensification of statin therapy results in a rapid reduction in atherosclerotic inflammation: results of a multicenter fluorodeoxyglucose-positron emission tomography/computed tomography feasibility study

J Am Coll Cardiol. 2013 Sep 3;62(10):909-17. doi: 10.1016/j.jacc.2013.04.066. Epub 2013 May 30.

Abstract

Objectives: The study sought to test whether high-dose statin treatment would result in greater reductions in plaque inflammation than low-dose statins, using fluorodeoxyglucose-positron emission tomography/computed tomographic imaging (FDG-PET/CT).

Background: Intensification of statin therapy reduces major cardiovascular events.

Methods: Adults with risk factors or with established atherosclerosis, who were not taking high-dose statins (n = 83), were randomized to atorvastatin 10 versus 80 mg in a double-blind, multicenter trial. FDG-PET/CT imaging of the ascending thoracic aorta and carotid arteries was performed at baseline, 4, and 12 weeks after randomization and target-to-background ratio (TBR) of FDG uptake within the artery wall was assessed while blinded to time points and treatment.

Results: Sixty-seven subjects completed the study, providing imaging data for analysis. At 12 weeks, inflammation (TBR) in the index vessel was significantly reduced from baseline with atorvastatin 80 mg (% reduction [95% confidence interval]: 14.42% [8.7% to 19.8%]; p < 0.001), but not atorvastatin 10 mg (% reduction: 4.2% [-2.3% to 10.4%]; p > 0.1). Atorvastatin 80 mg resulted in significant additional relative reductions in TBR versus atorvastatin 10 mg (10.6% [2.2% to 18.3%]; p = 0.01) at week 12. Reductions from baseline in TBR were seen as early as 4 weeks after randomization with atorvastatin 10 mg (6.4% reduction, p < 0.05) and 80 mg (12.5% reduction, p < 0.001). Changes in TBR did not correlate with lipid profile changes.

Conclusions: Statin therapy produced significant rapid dose-dependent reductions in FDG uptake that may represent changes in atherosclerotic plaque inflammation. FDG-PET imaging may be useful in detecting early treatment effects in patients at risk or with established atherosclerosis.

Trial registration: ClinicalTrials.gov NCT00703261.

Keywords: 2-18F-fluoro-2-deoxy-D-glucose; AC; C-reactive protein; CRP; FDG; LDL; MDS; PET/CT; SUV; TBR; atherosclerosis; atorvastatin; attenuation correction; inflammation; low-density lipoprotein; most diseased segment; plaque; positron emission tomography-computed tomographic imaging; standardized uptake value; statins; target-to-background ratio.

Publication types

  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Aorta, Thoracic / diagnostic imaging*
  • Aorta, Thoracic / pathology
  • Atherosclerosis / diagnostic imaging
  • Atherosclerosis / drug therapy*
  • Atorvastatin
  • Carotid Arteries / diagnostic imaging*
  • Carotid Arteries / pathology
  • Double-Blind Method
  • Feasibility Studies
  • Female
  • Fluorodeoxyglucose F18
  • Heptanoic Acids / administration & dosage
  • Heptanoic Acids / therapeutic use*
  • Humans
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors / administration & dosage
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors / therapeutic use*
  • Inflammation / diagnostic imaging
  • Inflammation / drug therapy*
  • Male
  • Middle Aged
  • Multimodal Imaging / methods
  • Plaque, Atherosclerotic / diagnostic imaging
  • Plaque, Atherosclerotic / drug therapy*
  • Positron-Emission Tomography / methods
  • Pyrroles / administration & dosage
  • Pyrroles / therapeutic use*
  • Treatment Outcome

Substances

  • Heptanoic Acids
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors
  • Pyrroles
  • Fluorodeoxyglucose F18
  • Atorvastatin

Associated data

  • ClinicalTrials.gov/NCT00703261