1. Slide Source: Lipids Online Slide Library www.lipidsonline.org Reversal of Atherosclerosis with Aggressive Lipid Lowering (REVERSAL) Nissen SE et al. JAMA 2004;291:1071-1080. 654 patients with symptomatic CAD with angiographic stenosis >20% and LDL-C 125–210 mg/dL; 502 with evaluable follow-up Randomization to pravastatin 40 mg/d or atrovastatin 80 mg/d for 18 months IVUS performed at baseline and 18 months Primary endpoint: percent change in atheroma volume assessed with IVUS

2. Slide Source: Lipids Online Slide Library www.lipidsonline.org Baseline Characteristics: REVERSAL Pravastatin (n=249) Atorvastatin (n=253)p Age, y56.655.8.37 Male73%71%.69 White87%90%.54 Current smoker27%26%.97 Past or nonsmoker74%.97 Hx HTN70%68%.70 Prior statin use32%25%.06 Hx DM18%20%.65 LDL-C, mg/dL 150.2 ± 25.9150.2 ± 27.9.99 HDL-C, mg/dL 42.9 ± 11.442.3 ± 9.9.51 TG, mg/dL 197.7 ± 105.6197.2 ± 95.7.96 CRP, mg/L3.0 ± 2.92.8 ± 3.0.46 Nissen SE et al. JAMA 2004;291:1071-1080.

3. Slide Source: Lipids Online Slide Library www.lipidsonline.org PravastatinAtorvastatin REVERSAL: Primary and Secondary Endpoints— Change in Atheroma Volume Assessed by IVUS Change from Baseline, % p=.02 p=.02 p<.001 2.7 –0.4 4.4 –0.9 Nissen SE et al. JAMA 2004;291:1071-1080. p<.001 1.6 0.2 p=.01 p=.001 1° endpoint: Percent change in atheroma volume Total atheroma volume Change in percent atheroma volume p=.98p=.72 p=.18

4. Slide Source: Lipids Online Slide Library www.lipidsonline.org PravastatinAtorvastatin REVERSAL: Lipid and CRP Changes Change from Baseline, % –34.1 Nissen SE et al. JAMA 2004;291:1071-1080. p<.001 TCLDL-CHDL-CTG Apo B-100 CRP –18.4 –25.2 –46.3 5.6 2.9 –6.8 –20.0 –22.0 –39.1 –5.2 –36.4 p<.001p=.06p<.001

5. Slide Source: Lipids Online Slide Library www.lipidsonline.org Pravastatin 40 mg Atorvastatin 80 mg REVERSAL: Final Lipids on Treatment Mg/dL Nissen SE et al. JAMA 2004;291:1071-1080. LDL-C 110.4 Apo B-100TGHDL-C 78.9 118.1 91.8 165.8 148.4 44.6 43.1

6. Slide Source: Lipids Online Slide Library www.lipidsonline.org REVERSAL: Effects on LDL-C Nissen SE et al. JAMA 2004;291:1071-1080. LDL-C was reduced to a mean of 110 mg/dL with pravastatin 40 mg and 79 mg/dL with atorvastatin 80 mg ATP III goal of LDL-C <100 mg/dL was achieved by 65% of pravastatin patients and 97% of atorvastatin patients