ASTEROID

A Study To evaluate the Effect of Rosuvastatin On Intravascular ultrasound- Derived 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.

*Patients with >50% luminal narrowing were excluded

ASTEROID: Study design

Nissen SE et al. JAMA. 2006;295:1556-65.

Angiographic CAD (>20% luminal narrowing*) Statin-naive

N = 507

Rosuvastatin 40 mg qd for 24 months

Primary efficacy parameters:• Change in % atheroma volume of target vessel• Change in total atheroma volume in most diseased 10-mm segment

Multicenter, open-label, blinded end point

IVUS assessment at baseline and study end

Completed trialN = 349

ASTEROID: Baseline characteristics

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.

N = 349

ASTEROID: Baseline characteristics

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

N = 349

Nissen SE et al. JAMA. 2006;295:1556-65.

ASTEROID: Treatment effect on lipids

204.0

130.4

43.1

133.8

60.8 49.00

50

100

150

200

250

300

Total-C LDL-C HDL-C

mg/dL

Baseline 24 months

Nissen SE et al. JAMA. 2006;295:1556-65.*P < 0.001 vs baseline

n = 346

**

3.2

1.3

0

1

2

3

4

5

LDL-C/HDL-C

53.2%

14.7%

33.8%

58.5%

ASTEROID: Treatment effect on primary efficacy parameters

Mean % atheroma volume (N = 349)

39.6 38.6

0

35

40

45

50

Baseline 24 months

Mean atheroma volume in most diseased segment

(n = 319)

65.159

0

60

70

80

90

100

Baseline 24 months

Nissen SE et al. JAMA. 2006;295:1556-65.

mm3

P < 0.001 P < 0.001

%

ASTEROID: Treatment-emergent adverse events

Nissen SE et al. JAMA. 2006;295:1556-65.

63 patients withdrew for adverse events,62 withdrew for other reasons*Causes of death: Renal failure (1), sudden cardiac

death (2), gastric carcinoma (1)

N = 507

Death*

MI

Stroke

Creatine kinase >5x ULN

Creatine kinase >10x ULN

ALT >3x ULN

4 (0.8)

10 (2.0)

3 (0.6)

6 (1.2)

0

9 (1.8)

Patients (%)

ASTEROID: Drug discontinuations

Nissen SE et al. JAMA. 2006;295:1556-65.

63 patients withdrew for adverse events,62 withdrew for other reasons*Angina, CHF, arrhythmias, other ischemic events

N = 507

Musculoskeletal complaints

GI complaints

Neoplasms

Creatine kinase

ALT or bilirubin

CV disorders*

19 (3.7)

2 (0.4)

2 (0.4)

2 (0.4)

2 (0.4)

22 (4.3)

Patients (%)

Relationship between ↓LDL-C and atheroma burden

Data from recent IVUS trials

Nissen SE et al. JAMA. 2006;295:1556-65.

Median Δin percent

atheroma volume(%)

1.8

–0.6

CAMELOTPlacebo

REVERSALAtorvastatin

REVERSALPravastatin

A-PlusPlacebo

ASTEROIDRosuvastatin

r2 = 0.97P < 0.001

0

0.6

1.2

–1.20 60 70 80 90 100 110 120

Mean LDL-C (mg/dL)

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.