Effect of intensive atorvastatin therapy on coronary atherosclerosis progression, composition, arterial remodeling, and microvascular function

J Invasive Cardiol. 2012 Oct;24(10):522-9.

Abstract

Background: There is a discrepancy between the marked reduction in adverse events with statins and their modest effect on atheroma regression. We hypothesized that, in a Western population, high-dose atorvastatin will result in alterations in coronary atheroma composition, phenotype, and microvascular function.

Methods: Serial coronary radiofrequency intravascular ultrasound (VH-IVUS), coronary flow reserve (CFR), and hyperemic microvascular resistance (HMR) were performed at baseline and after 6 months of treatment with 80 mg atorvastatin in 20 patients with moderate coronary artery disease (CAD). For each VH-IVUS frame (n = 2249), changes in total plaque atheroma, composition, and phenotype (pathological intimal thickening, fibrotic plaque, fibroatheroma), and serial remodeling were assessed.

Results: Total serum cholesterol decreased from 186.0 mg/dL (interquartile range [IQR], 168.0 to 212.5 mg/dL) to 139.0 mg/dL (IQR, 124.3 to 151.3 mg/dL). Percent atheroma volume did not change significantly (-0.5% [IQR, -2.8% to 3.7%]; P=.90) and serial remodeling analysis demonstrated 40% constrictive, 24% incomplete, and 36% expansive patterns. There was a trend toward lower percent fibrous tissue (-3.47 ± 1.78%; P=.07) and percent fibro-fatty tissue (-2.52 ± 1.24%; P=.06) and increase in percent necrotic core (+2.74 ± 1.65%; P=.11) and percent dense calcium (+1.99 ± 0.81; P=.02), which translated into significantly less pathological intimal thickening (4% vs 12%; P<.0001) and more fibroatheromas (67% vs 57%; P<.0001) at follow-up compared to baseline. There were modest non-significant improvements in CFR (+0.26 [IQR, -0.37 to 0.76]; P=.23) and HMR (-0.22 [IQR, -0.56 to 0.28]; P=.12).

Conclusions: In this pilot study of Western patients with moderate CAD, high-dose atorvastatin resulted in alterations in coronary atheroma composition with corresponding changes in plaque phenotype and modest improvement in coronary microvascular function.

Trial registration: ClinicalTrials.gov NCT00576576.

Publication types

  • Clinical Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Anticholesteremic Agents / pharmacology
  • Anticholesteremic Agents / therapeutic use*
  • Atorvastatin
  • Cholesterol / blood
  • Coronary Artery Disease / diagnostic imaging
  • Coronary Artery Disease / drug therapy*
  • Coronary Artery Disease / physiopathology
  • Coronary Vessels / diagnostic imaging
  • Coronary Vessels / drug effects
  • Coronary Vessels / physiopathology*
  • Disease Progression*
  • Dose-Response Relationship, Drug
  • Female
  • Follow-Up Studies
  • Heptanoic Acids / pharmacology
  • Heptanoic Acids / therapeutic use*
  • Humans
  • Male
  • Microvessels / diagnostic imaging
  • Microvessels / drug effects
  • Microvessels / physiopathology*
  • Middle Aged
  • Phenotype
  • Pilot Projects
  • Pyrroles / pharmacology
  • Pyrroles / therapeutic use*
  • Regional Blood Flow / drug effects
  • Regional Blood Flow / physiology
  • Retrospective Studies
  • Treatment Outcome
  • Ultrasonography, Interventional
  • Vascular Resistance / drug effects
  • Vascular Resistance / physiology

Substances

  • Anticholesteremic Agents
  • Heptanoic Acids
  • Pyrroles
  • Cholesterol
  • Atorvastatin

Associated data

  • ClinicalTrials.gov/NCT00576576