Virtual Histology Findings and Effects of Varying Doses of Atorvastatin Treatment

Study Overview
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Brief Summary
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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.

Detailed Description
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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.

Official Title
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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

Conditions
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Coronary Disease, Ultrasonography, Interventional, Hydroxymethylglutaryl-CoA Reductase Inhibitors

Intervention / Treatment
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* Drug: Atorvastatin 10mg versus 40mg.


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: 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. Exclusion Criteria: 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.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 85 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Atorvastatin 10mg low dose<br>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. | Drug: Atorvastatin 10mg versus 40mg.<br>* 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.<br>* Other names: Lipitor 10mg versus 40mg daily for 6 months.;|
| Active Comparator: Atorvastatin 40mg moderate dose<br>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. | Drug: Atorvastatin 10mg versus 40mg.<br>* 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.<br>* Other names: Lipitor 10mg versus 40mg daily for 6 months.;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The primary endpoint would be the 6-month angiographic and VH-IVUS restudy findings. | 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. | 6 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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. | As described in the Title above. | Throughout the 6 months study period. | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Volumetric virtual histology intravascular ultrasound., Statin-naive patient., Varying doses atorvastatin., Clinical outcomes.