Transcript ASTEROID

ASTEROID
A Study To evaluate the Effect of
Rosuvastatin On Intravascular ultrasoundDerived coronary atheroma burden
ASTEROID: Background and hypothesis
• Aggressive lipid modification has demonstrated regression and/or
reduced progression of stenotic lesions by quantitative coronary
angiography
• IVUS trials have shown a halting of progression of atherosclerosis
during statin treatment; however, none have provided convincing
evidence of regression
• Does very aggressive statin treatment with rosuvastatin 40 mg,
designed to simultaneously  LDL-C and  HDL-C, result in
regression of coronary atherosclerosis?
Nissen SE et al. JAMA. 2006;295:1556-65.
ASTEROID: Study design
Angiographic CAD (>20% luminal narrowing*)
Statin-naive
N = 507
Multicenter, open-label,
blinded end point
IVUS assessment at
baseline and study end
Rosuvastatin 40 mg qd for 24 months
Completed trial
N = 349
Primary efficacy parameters:
• Change in % atheroma volume of target vessel
• Change in total atheroma volume in most diseased 10-mm segment
*Patients with >50% luminal narrowing
were excluded
Nissen SE et al. JAMA. 2006;295:1556-65.
ASTEROID: Baseline characteristics
N = 349
Age mean (years)
58.5
Male (%)
70.2
White (%)
96.8
BMI (kg/m2)
(interquartile range)
28.4
(25.8–31.4)
Nissen SE et al. JAMA. 2006;295:1556-65.
ASTEROID: Baseline characteristics
N = 349
Patients (%)
Medical history
Hypertension
Diabetes
ACS
Prior MI
96.0
13.2
17.2
24.6
Concomitant medications
Aspirin
ACEIs
ARBs
Nitrates
β-blockers
83.7
53.3
18.3
85.1
84.2
Nissen SE et al. JAMA. 2006;295:1556-65.
ASTEROID: Treatment effect on lipids
n = 346
5
300
33.8%
250
200
4
53.2%
204.0
14.7%
mg/dL 150
133.8
100
50
130.4
*
60.8
3
3.2
58.5%
2
*
1
1.3
43.1 49.0
0
0
Total-C
LDL-C
Baseline
24 months
*P < 0.001 vs baseline
HDL-C
LDL-C/HDL-C
Nissen SE et al. JAMA. 2006;295:1556-65.
ASTEROID: Treatment effect on primary efficacy
parameters
Mean % atheroma volume
(N = 349)
Mean atheroma volume in
most diseased segment
(n = 319)
50
100
45
P < 0.001
% 40
39.6
35
38.6
90
mm3 80
70
60
P < 0.001
65.1
0
0
Baseline
24 months
Baseline
59
24 months
Nissen SE et al. JAMA. 2006;295:1556-65.
ASTEROID: Treatment-emergent adverse events
N = 507
Patients (%)
Death*
4 (0.8)
MI
10 (2.0)
Stroke
3 (0.6)
Creatine kinase >5x ULN
6 (1.2)
Creatine kinase >10x ULN
0
ALT >3x ULN
9 (1.8)
63 patients withdrew for adverse events,
62 withdrew for other reasons
*Causes of death: Renal failure (1), sudden cardiac
death (2), gastric carcinoma (1)
Nissen SE et al. JAMA. 2006;295:1556-65.
ASTEROID: Drug discontinuations
N = 507
Patients (%)
Musculoskeletal complaints
19 (3.7)
GI complaints
2 (0.4)
Neoplasms
2 (0.4)
 Creatine kinase
2 (0.4)
 ALT or bilirubin
2 (0.4)
CV disorders*
22 (4.3)
63 patients withdrew for adverse events,
62 withdrew for other reasons
*Angina, CHF, arrhythmias, other ischemic events
Nissen SE et al. JAMA. 2006;295:1556-65.
Relationship between ↓LDL-C and atheroma
burden
Data from recent IVUS trials
1.8
CAMELOT
Placebo
1.2
Median Δ
in percent
atheroma volume
(%)
REVERSAL
Pravastatin
0.6
A-Plus
Placebo
REVERSAL
Atorvastatin
0
–0.6
r2 = 0.97
P < 0.001
ASTEROID
Rosuvastatin
–1.2
0
60
70
80
90
100
110
120
Mean LDL-C (mg/dL)
Nissen SE et al. JAMA. 2006;295:1556-65.
ASTEROID: Summary
• Aggressive statin treatment with rosuvastatin (40 mg)
achieved significant changes in lipid levels
– LDL-C lowered to 60.8 mg/dL (53.2%)
– HDL-C raised to 49 mg/dL (14.7%)
• These changes were associated with significant
regression of coronary atherosclerosis assessed via
prespecified IVUS end points
• Benefits were also observed in all prespecified
subgroups (including age, sex, BMI, history of diabetes)
Nissen SE et al. JAMA. 2006;295:1556-65.
ASTEROID: Implications
• Aggressive lipid-modulating strategies in patients with
CAD can reverse the atherosclerotic disease process
• Therapies designed to simultaneously lower LDL-C
while raising HDL-C have the potential to substantially
reduce atheroma burden
Nissen SE et al. JAMA. 2006;295:1556-65.
Blumenthal R et al. JAMA. 2006;295:1583-4.