Virtual Histology Findings and Effects of Varying Doses of Atorvastatin Treatment (VENUS)

• The primary endpoint would be the 6-month angiographic and VH-IVUS restudy findings. [ Time Frame: 6 months ] [ Designated as safety issue: No ]
  Our hypothesis was plaque regression and virtual histology intravascular ultrasound (VH-IVUS) plaque modification with statin therapy could be statin dose dependent, and may affect clinical outcomes. 2 clinically realistic doses of atorvastatin 10mg and 40mg were chosen in statin-naïve patients without previous myocardial infarction. The primary endpoint of this study would therefore be the 6 months angiographic and IVUS follow-up, looking at the volumetric gray-scale IVUS and VH-IVUS findings at 6 months for the whole cohort as well as the differences between the 2 groups.
  
  

• The secondary endpoint would be the occurrence of any major adverse cardiac events at 6 months (including any death, myocardial infarction or need for revascularization) as routinely monitored after all percutaneous interventional procedures. [ Time Frame: Throughout the 6 months study period. ] [ Designated as safety issue: No ]
  As described in the "Title" above.
  
  

Statin therapy, especially at intensive doses, is beneficial in atherosclerotic coronary disease. Detecting subtle plaque regression after statin therapy is difficult by coronary angiogram; intravascular ultrasound (IVUS) is a far better method. Volumetric IVUS has been used in statin trials to evaluate plaque regression. Intensive statin therapy in the REVERSAL Trial and ASTEROID Trial appeared to achieve better regression outcomes. Stable fibrous plaque is likely to be responsible for stable ischemia, while unstable plaque (large lipid core, calcified nodule and necrotic core), thin-cap fibroatheroma, plaque erosion and plaque rupture may be responsible for acute coronary syndrome (ACS). In vivo tissue characterization of plaque composition is therefore important, yet in this regard grayscale IVUS is insufficient. The development of Virtual Histology (VH) utilizing IVUS generated radiofrequency backscattering signals to virtually separate plaque composition into 4 components corresponding to histopathology has made possible in vivo assessment of plaque composition and stability. We believed plaque regression and VH-IVUS plaque modification with statin therapy could be statin dose dependent, and may affect clinical outcomes. This study was designed to prove our hypothesis, utilizing VH-IVUS.

This study is the first prospective, randomised, double-blinded pilot study designed to investigate the varying statin dose effects on plaque regression and VH composition modulation. For ethical reasons, a placebo arm was not designed. Based on available data, clinically realistic doses of atorvastatin 10mg (low dose) and 40mg (moderate dose) were chosen. Only statin-naïve patients without previous history of myocardial infarction (MI) would be selected, aiming to show the "pure" effects of varying doses of statin and to better reveal the subtle differences in the changes.