Reduction in YEllow Plaque by Aggressive Lipid LOWering Therapy

Phase 4

Completed

Conditions: Coronary Artery Disease

Interventions: Drug: Aggressive lipid therapy
Drug: standard of care lipid therapy

Registration Number: NCT01567826

Lead Sponsor: Annapoorna Kini

Brief Summary: The study will assess the regression of yellow plaque content of the lipid pool after aggressive lipid therapy by utilizing NIR spectroscopy. Statin therapy using Rosuvastatin 10-40 mg will be compared to the statin therapy of either Atorvastatin or Simvastatin. This is a single site study. A total of 100 subjects will randomized, of which 40 will receive intensive lipid therapy (Rosuvastatin 40mg) and 40 will receive standard care lipid lowering therapy.

Detailed Description: Coronary artery disease (CHD) remains to be a leading cause of death in most countries (1) (2). It is well known that reducing cholesterol level by statin therapy is associated with significant reduction in plaque burden. REVERSAL (3) and ASTEROID (4) trials showed that in patients with coronary artery disease lipid-lowering with atorvastatin or rosuvastatin respectively reduced progression of coronary atherosclerosis and even cause repression of some lesions. CHD clinical events are related to plaque instability due to lipid content within the atherosclerotic plaque. High dose atorvastatin has shown to reduce the plaque lipid contents on serial IVUS analysis at 12 months. Therefore reduction in lipid content and thereby the plaque burden by lipid lowering therapy may stabilize the plaque and reduce cardiovascular events. High sensitivity C-reactive Protein (HsCRP) is an inflammatory biomarker that independently predicts future vascular events. In JUPITER (5) trial rosuvastatin (Crestor) significantly reduced the incidence of major cardiovascular events in apparently healthy people with elevated HsCRP. IVUS was utilized to demonstrate change in coronary artery vessel wall morphology over a relatively short period of time, but provided no data on the lipid content in the vessel wall. The application of NIR spectroscopy to identify lipid deposition within coronary arteries has been validated in ex vivo studies. Infrared spectra are collected as follows: Light of discrete wavelengths from a laser is directed onto the tissue sample via glass fibers. Light scattered from the samples is collected in fibers and launched into a spectrometer. The plot of signal intensity as a function of wavelength was used to develop chemometric models to discriminate lipid-cores from non-atherosclerotic tissue, and from atherosclerotic tissue that is predominantly fibrotic and from blood elements.

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 87

Inclusion Criteria

Patient > 18 years of age and willing to participate
Stable patients who will undergo cardiac catheterization and PCI (intent to stent)
Patient is willing to go on a cholesterol lowering medication for the duration of the study and willing to change statin therapy to the randomized statin therapy regardless of previous statin therapy and dose (e.g. Atorvastatin 80 mg) Patients that are screened for this study and are receiving another Statin such as Pravachol will be required to be willing to change their therapy to Rosuvastatin as per is randomization. If patients are receiving another statin, such as pravachol, or any other agent, and are at appropriate Lipid levels, they will be permitted to continue this therapy (if randomized to the standard therapy arm). There are a virtually unlimited number of possible scenarios for potential combination of all Lipid lowering agents at the time of enrollment that patients may be taking.
Signed written Informed Consent
Women of childbearing potential must agree to be on an acceptable method of birth control/contraceptive such as barrier method (condoms/diaphragm); hormonal contraceptives (birth control pills, implants (Norplant) or injections (Depo-Provera)); Intrauterine Device; or abstinence (no sexual activity).
Fluency in English and/or Spanish

Exclusion Criteria

Patients who have acute myocardial infarction (Q wave or non-Q wave with CK-MB > 5 times above the upper normal (31.5 ng/ml) within 72 hours)
Patients who are in cardiogenic shock
Patients with left main disease or restenotic lesions
Patients with elevated CK-MB (> 6.5 ng/ml) or Tnl (> 0.5ng/L) at baseline
Patients with platelet count < 100,000 cell/mm3
Patients who have co-morbidity which reduces life expectancy to one year
Patients who are currently participating in another investigational drug/device study
Patients with known hypersensitivity to HMG CO-A reductase therapy (statins)
Patients with liver disease
Patient with creatinine > 2.0 mg/dL
Pregnant women and women of childbearing potential who intend to have children during the duration of the trial

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
aggressive lipid therapy	Aggressive lipid therapy	aggressive lipid therapy: Crestor
standard of care lipid therapy	standard of care lipid therapy	standard-care lipid-lowering therapy: Zocor or Lipitor

Primary Outcome Measures

Name	Time	Method
Lipiscan - Lipid Core Burden Index (LCBI)	at baseline and at 6-8 weeks after intervention	The regression of yellow plaque content from the atherosclerotic lipid pool after statin therapy by utilizing NIR spectroscopy as compared from baseline to 6-8 weeks after intervention. Spectroscopic information obtained from raw spectra was transformed into a probability of lipid core that was mapped to a red-to-yellow color scale, with the low probability of lipid shown as red and the high probability of lipid shown as yellow. Analyses were performed offline using the Matlab-based software, as previously published. Yellow pixels within the analyzed segment were divided by all viable pixels to generate the lipid-core burden index (LCBI). The maximal value of LCBI for each nonculprit obstructive lesion was recorded and used for comparison.
LCBI4mm Max	at baseline and at 6-8 weeks after intervention	LCBI4mm max = change in lipid-core burden index at the 4-mm maximal segment. Spectroscopic information obtained from raw spectra was transformed into a probability of lipid core that was mapped to a red-to-yellow color scale, with the low probability of lipid shown as red and the high probability of lipid shown as yellow. Yellow pixels within the analyzed segment were divided by all viable pixels to generate the lipid-core burden index (LCBI). The maximal value of LCBI for each nonculprit obstructive lesion was recorded and used for comparison.
Change in LCBI4mm Max	at baseline and at 6-8 weeks after intervention	Change in LCBI4mm max at 6-8 weeks after intervention as compared to baseline. LCBI4mm max = change in lipid-core burden index at the 4-mm maximal segment.
Change in LCBI, Lesion	at baseline and at 6-8 weeks post intervention	Change in LCBI at 6-8 weeks after intervention as compared to baseline

Secondary Outcome Measures

Name	Time	Method
Intravascular Ultrasound (IVUS) Parameters	at baseline and at 6-8 weeks after intervention	Change in atheroma volume and lumen CSA on IVUS as related to change in yellow plaque index as compared from baseline to 6-8 weeks after intervention. Data not analyzed. Data not available.
Fractional Flow Reserve (FFR) Value	at baseline and at 6-8 weeks after intervention	Change in FFR as related to change in yellow plaque index as compared from baseline to 6-8 weeks after intervention. Fractional flow reserve (FFR), defined as the ratio of maximum flow in the presence of a stenosis to normal maximum flow, is a lesion-specific index of stenosis severity that can be calculated by simultaneous measurement of mean arterial, distal coronary, and central venous pressure.
Diameter Stenosis	Baseline and 6-8 weeks post intervention	Percentage stenosis of vessel diameter in the analysis segment of nontarget lesions as measured by angiography that remained \>70%, after successful PCI of the target lesion.
Post PCI Cardiac Enzymes	at 6-8 weeks after intervention	Correlation of yellow plaque index with post procedure CK-MB, Troponin-I release.
Major Adverse Cardiac Events (MACE)	at 6-8 weeks after intervention	MACE defined as a combined clinical endpoint of death, MI (Q wave or non Q-wave with CK-MB \>3 times above the upper normal limit (48 U/L), urgent revascularization or stroke at 30 days and 1 year. Details reported in adverse events section.
Blood Chemistry - HsCRP	at baseline and at 6-8 weeks after intervention	Correlation of yellow plaque index with changes in levels of blood HsCRP as compared from baseline to 6-8 weeks after intervention