2. (N=488) Simvastatin in Patients With Prior Cerebrovascular Disease: HPS *29% RRR, p=0.001 Heart Protection Study Collaborative Group. Lancet. 2004;363:757-767. N=169N=170 N=406 24.7* Major Vasular Events 29.8 10.310.4 Simvastatin Placebo Stroke 2

3. SPARCL Trial of Secondary Stroke Prevention: Study Design 3 540 Primary End Points 4731 Patients 205 sites worldwide Previously documented stroke or TIA within 6 months No history of CHD LDL-C levels ≥100 mg/dL and ≤190 mg/dL Patient Population Primary End Point Time to the First Occurrence of a Fatal or Nonfatal Stroke Atorvastatin 80 mg/day SPARCL Investigators. Cerebrovasc Dis. 2003;16:389-395. Pravastatin 40 mg Double-Blind Period

4. SPARCL Primary End Point: Time to Fatal or Nonfatal Stroke 4 *Treatment effect from Cox proportional hazards models with prespecified adjustment for geographical region, entry event, time since entry event, gender, and baseline age. Amarenco P et al. N Engl J Med. 2006;355:549-559. Placebo (n= 2366) Mean LDL-C = 128 mg/dL (3.3 mmol/L) Atorvastatin 80 mg (n= 2635) Mean LDL-C = 73 mg/dL (1.9 mmol/L) Adjusted HR (95% CI)* = 0.84 (0.71, 0.99), p = 0.03 16% RR Years Since Randomization Fatal or Non-Fatal Stroke, % 0123456 12% 16% Placebo Atorvastatin 8% 4% 0%

5. *Treatment effect from Cox proportional hazards models with prespecified adjustment for geographical region, entry event, time since entry event, gender, and baseline age. Amarenco P et al. N Engl J Med. 2006;355:549-559. 5 SPARCL Secondary End Point: Time to Major Coronary Event 5 Years Since Randomization Adjusted HR (95% CI)* = 0.65 (0.49, 0.87), p = 0.003 35% RR Major Coronary Event, % 0123456 0% 2% 4% 6% 8% Placebo Atorvastatin

6. SPARCL: Benefit/Risk Atorvastatin n = 2365 Placebo n = 2366 Atorvastatin n = 2365 Placebo n = 2366 Incidence (%) Stroke and Major Coronary Events Major Coronary Event Ischemic Stroke Hemorrhagic Stroke Unclassified Stroke P = 0.03 11.2% 13.1% 14.1% 17.2% P=0.002 Amarenco P. Exp Op Pharmacotherapy. 2007;8:2789-2797. 6 Stroke

7. Effect of Atorvastatin on Stroke In SPARCL Patients with Diabetes 7 *Adjusted for entry event, time since entry event, gender, age, and geographic region Callahan A, Welch KMA, Amarenco P, et al. 70 100 90 80 Percentage of Patients Free of EndPoints Placebo Atorvastatin 80 mg 012345 Years Since Randomization 6 HR = 0.70 (95% CI, 0.50, 0.98), P = 0.0387* Log-rank P = 0.0377 RR: 30%