Virtual histology evaluation of atherosclerosis regression during atorvastatin and ezetimibe administration: HEAVEN study

Circ J. 2012;76(1):176-83. doi: 10.1253/circj.cj-11-0730. Epub 2011 Nov 10.


Background: There is no study focusing on changes in coronary atherosclerosis during dual lipid-lowering therapy with statin and ezetimibe.

Methods and results: Eighty-nine patients with stable angina randomized in a 1:1 ratio to Group A (aggressive therapy: atorvastatin 80mg, ezetimibe 10mg) and Group S (standard therapy) were analyzed. Treatment period was 12 months. Coronary arteries were examined by intravascular ultrasound and virtual histology. We found a decrease in the percent atheroma volume (PAV) (-0.4%) in Group A compared with an increase (+1.4%) in Group S (P=0.014) and this was accompanied by an increased frequency of combined atherosclerosis regression (increased lumen volume+decreased PAV) in group A (40.5%) compared with group S (14.9%) (P=0.007). The target low-density lipoprotein cholesterol level <2mmol/L, presence of at least 4 of 5 atherosclerotic risk factors, and decreased level of vascular cellular adhesive molecule were independent predictors of plaque regression. There were no significant differences in plaque composition between the 2 groups over the study duration. However, during analysis of the 2 groups together, fibrous and fibro-fatty tissues decreased and dense calcification and necrotic core increased during follow-up.

Conclusions: Dual lipid-lowering therapy starts atherosclerosis regression, but does not lead to significant changes in plaque composition. The continuous shift in plaque from fibro and fibro-fatty to necrotic with calcification was present in both groups.

Publication types

  • Randomized Controlled Trial
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Anticholesteremic Agents / therapeutic use
  • Atorvastatin
  • Azetidines / therapeutic use*
  • Cell Adhesion Molecules / metabolism
  • Cholesterol / metabolism
  • Coronary Artery Disease / diagnostic imaging
  • Coronary Artery Disease / drug therapy*
  • Coronary Artery Disease / pathology*
  • Coronary Vessels / diagnostic imaging
  • Coronary Vessels / metabolism
  • Coronary Vessels / pathology*
  • Disease Progression
  • Drug Therapy, Combination
  • Ezetimibe
  • Female
  • Heptanoic Acids / therapeutic use*
  • Humans
  • Lipoproteins / metabolism
  • Male
  • Middle Aged
  • Plaque, Atherosclerotic / diagnostic imaging
  • Plaque, Atherosclerotic / drug therapy*
  • Plaque, Atherosclerotic / pathology*
  • Pyrroles / therapeutic use*
  • Single-Blind Method
  • Treatment Outcome
  • Ultrasonography, Interventional


  • Anticholesteremic Agents
  • Azetidines
  • Cell Adhesion Molecules
  • Heptanoic Acids
  • Lipoproteins
  • Pyrroles
  • lipoprotein cholesterol
  • Cholesterol
  • Atorvastatin
  • Ezetimibe