A 6 month randomized, double blind, placebo controlled, multi-center trial of high dose atorvastatin on myocardial perfusion abnormalities by positron emission tomography in coronary artery disease

Am Heart J. 2008 Feb;155(2):245-53. doi: 10.1016/j.ahj.2007.10.025. Epub 2007 Dec 19.

Abstract

Background: In coronary artery disease (CAD), statins decrease morbidity and mortality but changes in myocardial perfusion abnormalities remain poorly defined.

Methods: We completed a randomized, double blind, placebo controlled, multi-center trial of 145 patients, 43 to 86 years old, with CAD from seven community and academic centers for cardiac positron emission tomography (PET) randomized to 6 months of atorvastatin 80 mg daily (72 patients) or placebo (73 patients). PET scans were obtained at baseline, 6 weeks and 6 months using N-13 ammonia or Rb-82 at rest and after dipyridamole or adenosine stress, submitted to the core PET laboratory in Houston. Change in stress induced perfusion defects from baseline to follow-up PET scans was scored by two independent, double blinded readers and by automated quantitative software.

Results: Total and LDL cholesterol decreased by 37% and 51%, respectively in atorvastatin but not placebo groups (P < .05). The primary endpoint, quantitative severity (lowest mean quadrant activity), showed no significant difference between treatment and placebo. The secondary endpoint, predefined blinded visual change scores, improved significantly after atorvastatin compared to placebo at six months (P = .02). Ad-hoc subgroup analysis showed interaction between quantitative defect size and treatment response with perfusion defects in the upper tertile of size by automated software improving more in atorvastatin than placebo groups (P = .016).

Conclusion: The primary endpoint, quantitative severity of myocardial perfusion abnormalities by PET, did not improve after 6 months of atorvastatin 80 mg daily compared to placebo. The secondary endpoint of predefined blinded visual change scores significantly improved, as did a subgroup in the upper tertile of defect size, compared to placebo.

Publication types

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

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Atorvastatin
  • Coronary Artery Disease / complications
  • Coronary Artery Disease / diagnostic imaging*
  • Coronary Circulation
  • Coronary Vessels
  • Double-Blind Method
  • Heart / diagnostic imaging
  • Heptanoic Acids / administration & dosage*
  • Humans
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors / administration & dosage*
  • Middle Aged
  • Myocardial Ischemia / diagnostic imaging*
  • Myocardial Ischemia / etiology
  • Positron-Emission Tomography*
  • Prospective Studies
  • Pyrroles / administration & dosage*

Substances

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