The Effects of Atorvastatin on Vulnerable Plaques in Untreated Dyslipidemic Patients.

Hyperlipidemia Clinical Trial

Official title:

Statin-Induced Vulnerable Plaque Regression After Atorvastatin Treatment: Serial Evaluation by 18F-Fluorodeoxyglucose Positron Emission Tomography Study

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00172419
• Other study ID #: 931204
• Status: Completed
• Phase: N/A
• First received: September 12, 2005
• Last updated: January 2, 2009
• Start date: March 2007
• Est. completion date: December 2008

Study information

• Verified date: December 2008
• Source: National Taiwan University Hospital
• Contact: n/a
• Is FDA regulated: No
• Health authority: Taiwan: Department of Health
• Study type: Interventional

Clinical Trial Summary

Inflammation is important in the both pathogenesis and outcome of atherosclerosis. Plaques containing numerous inflammatory cells, particular macrophages, have a high risk of rupture.We hypothesize that statin-induced plaque regression could be monitored clinically by use of FDG PET/CT approach, and can be detected noninvasively earlier than previously reported.

Description:

Cardiovascular events are the leading cause of death in developed countries worldwide, including Taiwan. The disruption of atherosclerotic plaques and the subsequent formation of thrombi are currently recognized as the major cause of morbidity and mortality of cardiovascular diseases. Therefore, early detection of vulnerable plaques is clinically important for risk stratification and also to provide early treatment. Several imaging approaches have been adapted to detect vulnerable plaques, including conventional X-ray contrast angiography, catheter capable of detecting temperature heterogeneity, infrared light or pH heterogeneity, ultrasonography (including intravascular ultrasound), high-resolution computed tomography and MRI. However, most of them are based on morphologic characteristics of atheroma. Moreover, although statin-induced lipid lowering and clinical benefits may occur in a matter of weeks, stain-mediated plaque volume regression has been measured in terms of years after the initiation of statin therapy. These discrepancies highlight the need for greater insight into the mechanisms and time course of statin-induced plaque regression.

As we know, inflammation may play a significant role in the pathogenesis and progression of atherosclerosis and subsequent vulnerable plaque rupture. Recently, 18F-fluorodeoxyglucose (FDG) positron emission tomography (PET), by use of 18FDG taken up by surrounding macrophages and smooth muscle cells, has been reported to detect atherosclerotic lesions by bio-pathologic functions. More and more evidence showed that FDG uptake is a marker of hypermetabolic state of atheromatous plaques, which is related to dense cellular infiltrate, and contributes to the identification of a subgroup of patients at high risk of complications. Recently, a combined PET/CT is emerged as a promising modality and is now beginning to be used more routinely in clinical situation, providing better localization and detecting calcification at the same time. Therefore, the use of FDG PET/CT might be a more sensitive and quantification method to monitor the inflammatory activity of vulnerable plaque after aggressive statin treatment. It could also provide the mechanism of early beneficial effects of statin treatment.

Our subject is to investigate prospectively the statin effects of lipid lowering and anti-inflammatory on human atherosclerotic lesions. We hypothesize that statin-induced plaque regression could be monitored clinically by use of FDG PET/CT approach, and can be detected noninvasively earlier than previously reported, and providing information of early statin efficacy caused by stabilization of vulnerable plaque without affecting the lumen size.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 43
• Est. completion date: December 2008
• Est. primary completion date: December 2008
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 30 Years to 80 Years

Eligibility

Inclusion Criteria: Untreated dyslipidemic (LDL cholesterol >110 mg/dl) subjects with documented atherosclerosis in at least 1 vascular territory: at least moderate (?4.0mm) aortic atherosclerosis by transesophageal echocardiography or CT/MRI, angiographically documented with coronary artery stenosis (?50% luminal stenosis), ultrasonographically documented significant extracranial arterial stenosis (?50%), history of ischemic stroke and transient ischemic attack (TIA), or documented peripheral vascular disease. Exclusion Criteria: Acute illness,infection, inflammation or major systemic diseases, T-Bil >3 mg/dl, or Creatinine >3 mg/dl.

Study Design

Endpoint Classification: Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Hyperlipidemia
• Hyperlipidemias

Intervention

Drug:
• Atorvastatin
Atorvastatin, 40 mg/day for 12 weeks

Locations

Country	Name	City	State
Taiwan	National Taiwan University Hospital	Taipei

Sponsors (3)

Lead Sponsor	Collaborator
National Taiwan University Hospital	National Science Council, Taiwan, Pfizer

Country where clinical trial is conducted

Taiwan, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Plaque location and activity at baseline, and compare with the follow-up scans site by site.		12 w	No
Secondary	Lipid profile		12 w	No
Secondary	Biomarkers		12 w	No