1. Clinical Overview Director, Stanford Stroke Center Stanford University Palo Alto, California Gregory W. Albers, MD

3. The Most Frequent Sites of Arterial and Cardiac Abnormalities Causing Ischemic Stroke Intracranial Atherosclerosis Carotid Plaque With Arteriogenic Emboli Aortic Arch Plaque Cardiogenic Emboli Penetrating Artery Disease Flow Reducing Carotid Stenosis Atrial Fibrillation Valve Disease Left Ventricular Thrombi Albers et al, Chest, 1998.

7. The High Cost of Stroke Annual Total 1998 Per Event* Direct Costs $28B $38,714 (care and treatment) Indirect Costs $15B $20,520 (lost productivity) Total $43B $59,234 *Based on 731,000 strokes/yr American Heart Association. 1998 Heart and Stroke Statistical Update . Dallas, TX:AHA, 1997. Broderick J et al. Stroke. 1998;29:415–421.

10. Efficacy of Antiplatelet Agents for Prevention of Stroke, MI, or Vascular Death Patient Relative Risk Odds Population Therapy Reduction (%) Reduction (%) All Vascular All antiplatelet 22 27 Diseases regimens Stroke/TIA All antiplatelet 17 22 regimens Stroke/TIA Aspirin 13 16 Source: Antiplatelet Trialists’ Collaboration, 1994: Algra and Van Gijn 1996. Risk Reductions

11. Efficacy of Antiplatelet Agents vs Placebo for Prevention of Stroke, MI, or Vascular Death in Stroke/TIA Patients Aspirin (all doses) 10 13 Ticlopidine 1 23 Dipyridamole + ASA 4 30 All Antiplatelet Agents 18 17 Relative Risk Antiplatelet Agent No. of Studies Reduction (%) Source: Algra and Van Gijn 1996; Gent et al. 1989; Tijssen, 1998; Antiplatelet Trialists’ Collaboration, 1994.

12. Relative Risk Reductions for Vascular Death, Stroke, MI from ASA Trials vs Placebo in Stroke/TIA Patients Algra and van Gijn (1996) J Neurol Neurosurg Psychiatr 60:197–199. 0.4 60% 0.6 40% 0.8 20% 1 0% 1.2 -20% 1.4 -40% 1.6 -60% RR and 95% CI ASA  100 mg (2 Studies) ASA  900 mg (7 Studies) ASA 300 mg (1 Study) ALL (10 Studies) RR = 13% RR = 9% RR = 14% RR = 13% Low vs Med: P = 0.75 Low vs High: P = 0.99 Med vs High: P = 0.71

13. ACE TRIAL Aspirin Efficacy by Dose Prevention of Vascular Events Following Carotid Endarterectomy Stroke or Death at 3 Months Stroke, MI, or Death at 3 Months 0 1 2 3 4 5 6 7 8 9 10 Low-Dose (N = 1395) (81 or 325 mg) High-Dose (N = 1409) (650 or 1300 mg) Event Rate (%) 5.7% 6.2% 7.1% 8.4% P = 0.030 P = 0.120 Taylor DW, Thorpe KE, for the ACE Trial Study Group. Presented at The Challenge of Stroke; The Lancet Conference; October 15–16, 1998. Montreal, Quebec, Canada; 1998.

18. Efficacy of Antiplatelet Agents in Patients With Cerebrovascular Disease Relative Risk Reduction vs Aspirin 7% 21%* 9% 23%* 22%* 8% 0 5 10 15 20 25 Stroke Stroke/MI/Vascular Death † Relative Risk Reduction (%) Clopidogrel (CAPRIE, N = 6431) Ticlopidine (TASS, N = 3069) ER-DP + ASA (ESPS-2, N = 3299) * Statistically significant. † Represents stroke/MI/Sudden Death for ESPS-2.

22. Risk Reductions Relative Risk: Rate of events on drug A Rate of events on drug B Odds Ratio: # of pts with event on drug A # of pts with event on drug B # of pts without event on drug A # of pts without event on drug B 100 patients treated for 1 year: 5 strokes on drug A, 10 strokes on drug B Relative Risk: 5% = .50 Relative Risk = 50% 10% Reduction (1-relative risk) Odds Ratio: 5 10 = .47 Odds Reduction = 53% 95 90 (1-odds ratio)  