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

Prof. Stephen Lee

Status and phase: Completed; Phase 4

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

Treatments: Drug: Atorvastatin 10mg versus 40mg.

Study type: Interventional

Funder types: Other; Industry

Identifiers

NCT01200056

HKCTR-517 (Other Identifier)

UW 07-266 (IRB HKU)

Details and patient eligibility

About

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.

Full 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.

Enrollment: 40 patients

Sex: All

Ages: 18 to 85 years old

Volunteers: No Healthy Volunteers

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.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

---

40 participants in 2 patient groups

Atorvastatin 10mg low dose

Active Comparator group

Description:

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.

Treatment:

Drug: Atorvastatin 10mg versus 40mg.

Atorvastatin 40mg moderate dose

Active Comparator group

Description:

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.

Treatment:

Drug: Atorvastatin 10mg versus 40mg.