|Virtual Histology Findings and Effects of Varying Doses of Atorvastatin Treatment
|A Prospective, Double-blinded, Randomised Study to Evaluate the Effects of Different Doses of Statin Treatment on Plaque Volume and Composition in Coronary Disease Determined by Virtual Histology Using Intravascular Ultrasound
While statin treatment may induce plaque regression, the effect of statin on plaque composition with varying doses is unknown. This study assessed such effects by volumetric virtual histology intravascular ultrasound (VH-IVUS).
In this prospective, randomized, double-blinded pilot study, statin-naïve patients with stable angina requiring percutaneous coronary intervention (PCI) were randomized to receive 6 months of either atorvastatin 10mg or 40 mg daily. VH-IVUS was performed in all non-PCI lesions at baseline and 6 months; all analyses were performed by core laboratory.
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.
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
- Coronary Disease
- Ultrasonography, Interventional
- Hydroxymethylglutaryl-CoA Reductase Inhibitors
|Drug: Atorvastatin 10mg versus 40mg.
2 arms comparing atorvastatin 10mg daily for 6 months to atorvastatin 40mg daily for 6 months. The primary endpoint would be the 6 months VH-IVUS findings and clinical outcomes.
Other Name: Lipitor 10mg versus 40mg daily for 6 months.
- Active Comparator: Atorvastatin 10mg low dose
Atorvastatin 10mg daily for 6 months and compared to atorvastatin 40mg daily in the other arm. The primary endpoint of 6 months VH-IVUS findings and clinical outcomes would be monitored and compared.
Intervention: Drug: Atorvastatin 10mg versus 40mg.
- Active Comparator: Atorvastatin 40mg moderate dose
Atorvastatin 40mg daily for 6 months and compared to atorvastatin 10mg daily in the other arm. The primary endpoint of 6 months VH-IVUS findings and clinical outcomes would be monitored and compared.
Intervention: Drug: Atorvastatin 10mg versus 40mg.
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|Same as current|
|November 2009 (Final data collection date for primary outcome measure)
- Patient aged 18 to 85 (not pregnant) requiring percutaneous intervention to coronary stenosis.
- Statin naive patient.
- No history of myocardial infarction. Angina free for at least 8 weeks.
- Any history of previous statin treatment and myocardial infarction
- Current acute coronary syndrome or in cardiogenic shock
- Surgical bypass candidate
- Chronic total occlusion and very tortuous calcified arteries precluding safe IVUS examination.
- Patient refused to give written informed consent.
|Sexes Eligible for Study:||All|
|18 Years to 85 Years (Adult, Older Adult)
|Contact information is only displayed when the study is recruiting subjects|
|UW 07-266 (IRB HKU)|
HKCTR-517 ( Other Identifier: Clinical Trials Centre, HKU (www.HKClinicalTrials.com) )
|Prof. Stephen Lee, The University of Hong Kong
|Prof. Stephen Lee
- Queen Mary Hospital, Hong Kong
|Principal Investigator:||Prof. Stephen WL LEE, MD FRCP FACC||Department of Medicine, the University of Hong Kong, Queen Mary Hospital, Hospital Authority|
|The University of Hong Kong