Clinical trial NCT01200056: Virtual Histology Findings and Effects of Varying Doses of Atorvastatin Treatment
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Coronary Disease
Ultrasonography, Interventional
Hydroxymethylglutaryl-CoA Reductase Inhibitors
Keywords: Volumetric virtual histology intravascular ultrasound.
Statin-naive patient.
Varying doses atorvastatin.
Clinical outcomes.
Lead sponsor: The University of Hong Kong
Sponsor class: OTHER
Collaborators: name: Queen Mary Hospital, Hong Kong
name: Pfizer
First posted: 2010-09-13
Enrollment: 40
Sex: ALL
Minimum age (years): 18
Maximum age (years): 85
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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: 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.

Eligibility criteria: 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.

Primary outcomes:
measure: The primary endpoint would be the 6-month angiographic and VH-IVUS restudy findings.
timeFrame: 6 months
Secondary outcomes:
measure: 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.
timeFrame: Throughout the 6 months study period.
Other outcomes:
Locations:
city: Hong Kong SAR
country: China
facility: Department of Medicine, the University of Hong Kong, Queen Mary Hospital, Hospital Authority
state: Hong Kong
Study officials:
affiliation: Department of Medicine, the University of Hong Kong, Queen Mary Hospital, Hospital Authority
name: Prof. Stephen WL LEE, MD FRCP FACC
role: PRINCIPAL_INVESTIGATOR
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