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:

*Patients with >50% luminal narrowing were excluded ASTEROID: Study design Nissen SE et al. JAMA. 2006;295: 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 trial N = 349

ASTEROID: Baseline characteristics Age mean (years)58.5 Male (%)70.2 White (%)96.8 BMI (kg/m 2 ) (interquartile range) 28.4 (25.8–31.4) Nissen SE et al. JAMA. 2006;295: N = 349

ASTEROID: Baseline characteristics Patients (%) Medical history Hypertension Diabetes ACS Prior MI Concomitant medications Aspirin ACEIs ARBs Nitrates β-blockers N = 349 Nissen SE et al. JAMA. 2006;295:

ASTEROID: Treatment effect on lipids Nissen SE et al. JAMA. 2006;295: *P < vs baseline n = 346 * *  53.2%  14.7%  33.8%  58.5%

ASTEROID: Treatment effect on primary efficacy parameters Nissen SE et al. JAMA. 2006;295: mm 3 P < %

ASTEROID: Treatment-emergent adverse events Nissen SE et al. JAMA. 2006;295: 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: 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) 22 (4.3) Patients (%)

Relationship between ↓LDL-C and atheroma burden Data from recent IVUS trials Nissen SE et al. JAMA. 2006;295: Median Δ in percent atheroma volume (%) 1.8 –0.6 CAMELOT Placebo REVERSAL Atorvastatin REVERSAL Pravastatin A-Plus Placebo ASTEROID Rosuvastatin r 2 = 0.97 P < – 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:

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: Blumenthal R et al. JAMA. 2006;295: