1. The American College of Cardiology Presented by Dr. Steven E. Nissen
ASTEROID Trial
A Study to Evaluate the Effect of Rosuvastatin on Intravascular Ultrasound-Derived Coronary Atheroma Burden (ASTEROID) Trial
Presented at
The American College of Cardiology
Scientific Session 2006
Presented by Dr. Steven E. Nissen

2. ASTEROID Trial: Background
The goal of this trial was to evaluate the effect of treatment with intensive statin therapy on intravascular ultrasound (IVUS).
Hypothesis: High-intensity rosuvastatin therapy, with the intention of reaching extremely low LDL levels, combined with higher HDL levels, may potentially regress coronary atherosclerosis.
Presented at ACC 2006

3. ASTEROID Trial: Study Design
1,183 patients screened for the presence of a coronary angiographic evaluated lesion >20%; IVUS target vessel stenosis <50% and not being treated with angioplasty with a minimum length of 40 mm; and statin-naïve. Excluding those with:
Uncontrolled triglyceride levels (≥500mg/dL) or poorly controlled diabetes (glycosylated hemoglobin levels ≥10%).
Open-label; mean age 58.5 years; mean follow-up at 2 years; 29% female.
All enrolled patients: 40 mg rosuvastatin, IVUS of a single vessel not intervened upon at baseline
n=507
Withdrawn consent, withdrawn for other reasons, adverse event (n=63)
n=158
Follow-up IVUS at 24 months
n=349
Primary Endpoint: 1) Change in percent atheroma volume and 2) change in nominal atheroma volume in the 10 mm subsegment with the greatest disease severity at baseline.
Secondary Endpoint: Change in normalized total atheroma volume for the entire artery.
Presented at ACC 2006

4. ASTEROID Trial: Primary Endpoint
Co-primary Endpoint of change in % atheroma volume (%)
The first co-primary endpoint, change in percent atheroma volume, was reduced by a mean of 0.98% (from 39.6% at baseline to 38.6% at 2 year follow-up, absolute change of %, p<0.001).
p<0.001
% Atheroma Volume
Presented at ACC 2006

5. ASTEROID Trial: Primary Endpoint cont.
Regression vs. progression change in % atheroma volume (%)
Regression in percent atheroma volume was observed in 63.6% of patients; whereas, progression was observed in 34.6%.
% patients
Presented at ACC 2006

6. ASTEROID Trial: Primary Endpoint cont.
Co-primary Endpoint of nominal atheroma volume in the 10 mm subsegement with the greatest disease severity at baseline (mm3)
The other co-primary endpoint, change in nominal atheroma volume in the 10 mm subsegment with the greatest disease severity at baseline, was also reduced (from 65.1mm3 at baseline to 59.0mm3 at 2 year follow-up, absolute change of
-6.1mm3, p<0.001).
p<0.001
mm3
Presented at ACC 2006

7. ASTEROID Trial: Principal Findings
Mean LDL level decrement and HDL level increment
(mg/dL)
LDL Levels were reduced from mg/dL at baseline to a mean of 60.8 mg/dL at 2 year follow-up (p<0.001), with 75% of patients achieving an LDL <70 mg/dL.
HDL levels were increased from 43.1 mg/dL at baseline to a mean of 49.0 mg/dL at follow-up (p<0.001).
p<0.001
p<0.001
LDL/HDL mg/dL
Presented at ACC 2006

8. ASTEROID Trial: Secondary Endpoint
Mean Normalized Total atheroma volume (mm3)
At follow-up, total atheroma volume was reduced from mm3 at baseline to mm3 (an absolute change of mm3).
mm3
Presented at ACC 2006

9. ASTEROID Trial: Adverse Events
Adverse events resulting in study drug discontinuation (%)
Musculoskeletal complaints (3.7%) and cardiovascular disorders (4.3%) were the adverse events that resulted in study drug discontinuation.
There were no cases of rhabdomyolysis. %
Presented at ACC 2006

10. ASTEROID Trial: Limitations
No control group
Those patients with a >50% stenosis within the target segment were excluded.
It is unknown whether statin-naïve patients are more likely to have a larger amount of atheroma regression compared to those already receiving statin therapy.
Presented at ACC 2006

11. ASTEROID Trial: Summary
Among patients with angiographic coronary disease, treatment with intensive statin therapy with rosuvastatin 40 mg was associated with atherosclerosis regression on IVUS at 2 year follow-up.
Prior IVUS studies have shown a reduction in atherosclerosis progression with intensive statin therapy compared with a more moderate lipid lowering regimen.
The authors attribute the regression in atheroma volume to the very large reductions in LDL and increases in HDL.
It should be noted that regression in atheroma volume in the most diseased 10 mm subsegment was observed even in patients with an average LDL of 100mg/dL (-6.9 mm3, p<0.001) and in those with an average HDL <35 mg/dL (-5.9 mm3, p<0.001).
The impact of aggressive lipid lowering on clinical events was not fully evaluated in this trial.
Presented at ACC 2006