Atherosclerosis
Conditions
Keywords
Atherosclerosis, vulnerable plaque, IVUS, shear stress
Brief summary
The purpose of this study is to evaluate the effects of Atorvastatin on the coronary atherosclerosis plaque morphology.
Detailed description
The primary goal of this project is to evaluate the effect of the cholesterol lowering drug Atorvastatin on the composition and character of coronary atherosclerosis (heart blockages). Atorvastatin is known to reduce cholesterol, reduce cardiac events, and halt the progression of coronary atherosclerosis. However, the reduction in cardiac events is out of proportion to the reductions in the total amount of atherosclerosis. Thus, the drug likely decreases cardiac events by changing the composition of the coronary atherosclerotic plaques. It is likely that the drug causes the heart blockage to change from a vulnerable plaque to a stable plaque. There are several features of vulnerable plaques that can be detected in arteries of the heart using intravascular ultrasound. The goal of this project is to examine the effects of atorvastatin on atherosclerosis plaque composition using this intravascular ultrasound in patients undergoing serial cardiac catheterizations. Our hypothesis is that atorvastatin will reduce the number of vulnerable plaques and increase the number of stable plaques seen by intravascular ultrasound. We plan to enroll a total of 20 patients. The patients will be evaluated by cardiac catheterization with intravascular ultrasound analysis and then be treated with atorvastatin for 6 months. These 20 patients will return to the cardiac catheterization laboratory 6 months later for a repeat catheterization with intravascular ultrasound evaluation. The secondary goal of this proposal is to evaluate in humans the relationship between coronary atherosclerosis (plaque buildup in the arteries of the heart) and wall shear stress (the force generated against the wall of the artery by the flow of blood). The reason for this sub-study is that there is great interest in understanding the characteristics that cause the progression of coronary atherosclerosis. Local forces such as shear stress may play an important role in the focal progression of vulnerable atherosclerotic plaques. Indeed, low shear stress is known to be an important factor in the early formation of atherosclerosis. However, the relationship of low shear stress to development and progression of advanced rupture prone (vulnerable) plaques has not been elucidated. Our hypotheses are: (1) Vulnerable plaques are more commonly located at areas of low shear stress(2) Vulnerable plaques at areas of low shear stress are more likely to progress over the following 6 months than plaques located in normal shear stress regions.
Interventions
DRUGAtorvastatin
Atorvastatin 80 mg a day
Sponsors
Pfizer
Emory University
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. The patients are eligible if they are undergoing catheterization for stable angina or acute coronary syndromes 2. At the time of catheterization the patient has a moderate coronary lesion in the proximal 60mm of an epicardial coronary artery 3. Moderate lesion is defined as a lesion deemed significant enough to warrant further evaluation using coronary flow reserve (CFR) and fractional flow reserve (FFR) by the treating physician 4. Patient must have decision making capacity and consented prior to the catheterization 5. Ages: All ages 6. Performance Status: all levels
Exclusion criteria
1\. Screening
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in Necrotic Core Volume | 6 months | Virtual Histology-Intravascular Ultrasound (VH-IVUS) defined necrotic core cross sectional area (CSA) measured in each VH-IVUS frame and averaged over length of studied vessel at baseline and follow -up. Change in necrotic core CSA between baseline and follow-up was calculated (subtracting the baseline value from the follow-up value). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change in Atheroma Volume | 6 months | Change in atheroma volume between baseline and follow-up is reported. This was derived by subtracting the baseline value from the 6-month value. |
| Change in Fibrous Plaque Volume | 6 months | Change in fibrous plaque volume between baseline and follow-up. This was derived by subtracting the baseline value from the 6-month value. |
Countries
United States
Participant flow
Recruitment details
27 subjects enrolled and followed up for 6 months All subjects were recruited between 2007 and 2009 at Emory University Hospital
Participants by arm
| Arm | Count |
|---|---|
| Atorvastatin All patients in this arm are given atorvastatin therapy.
Atorvastatin : Atorvastatin 80 mg a day | 20 |
| Total | 20 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Lost to Follow-up | 6 |
| Overall Study | Protocol Violation | 1 |
Baseline characteristics
| Characteristic | Atorvastatin |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 6 Participants |
| Age, Categorical Between 18 and 65 years | 14 Participants |
| Age, Continuous | 54 years |
| Region of Enrollment United States | 20 participants |
| Sex: Female, Male Female | 7 Participants |
| Sex: Female, Male Male | 13 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 0 / 27 |
| serious Total, serious adverse events | 0 / 27 |
Outcome results
Primary
Change in Necrotic Core Volume
Virtual Histology-Intravascular Ultrasound (VH-IVUS) defined necrotic core cross sectional area (CSA) measured in each VH-IVUS frame and averaged over length of studied vessel at baseline and follow -up. Change in necrotic core CSA between baseline and follow-up was calculated (subtracting the baseline value from the follow-up value).
Time frame: 6 months
Population: All enrolled patients with complete data set
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Atorvastatin | Change in Necrotic Core Volume | 0.07 mm^2 | Standard Deviation 0.06 |
Secondary
Change in Atheroma Volume
Change in atheroma volume between baseline and follow-up is reported. This was derived by subtracting the baseline value from the 6-month value.
Time frame: 6 months
Population: All enrolled patients with complete data set
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Atorvastatin | Change in Atheroma Volume | -4.0 mm^3 |
Secondary
Change in Fibrous Plaque Volume
Change in fibrous plaque volume between baseline and follow-up. This was derived by subtracting the baseline value from the 6-month value.
Time frame: 6 months
Population: All enrolled patients with complete data set
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Atorvastatin | Change in Fibrous Plaque Volume | -3.3 mm^3 |