1. Guidelines for Prevention of Stroke in Patients with Ischemic Stroke or Transient Ischemic Attack From the Stroke Council of the AHA Ralph L. Sacco, Chair; Robert Adams, Vice-Chair Greg Albers, Mark J. Alberts, Oscar Benavente, Karen Furie, Larry B. Goldstein, Philip Gorelick, Jonathan Halperin, Robert Harbaugh, S. Claiborne Johnston, Irene Katzan, Margaret Kelly-Hayes, Edgar J. Kenton, Michael Marks, Lee H. Schwamm, Thomas Tomsick Stroke 2006;37:577-617

2. Presentation Compiled by the AHA/ASA Professional Education Committee Susan C. Fagan, Chair Deborah Bergman Glenn D. Graham S. Claiborne Johnston Karen Johnston Edgar J. Kenton Dawn Kleindorfer Creed Pettigrew Kathryn Taubert, Staff Scientist Karen Modesitt, Staff

3. Introduction This slide set was adapted from the AHA/ASA Guidelines for Prevention of Stroke in Patients with Ischemic Stroke or Transient Ischemic Attack. From the American Heart Association/American Stroke Association Council on Stroke Co-Sponsored by the Council on Cardiovascular Radiology and Intervention Affirmed by the American Academy of Neurology The full-text guidelines are available on the Web site of the AHA ( www.americanheart.org )

4. Introduction Since the 1999 AHA Stroke Council guidelines for the secondary prevention of stroke, important evidence from clinical trials has emerged that further supports and broadens the options for aggressive risk reduction therapies. The secondary prevention patient population to be addressed includes those with prior stroke or transient ischemic attack, regardless of etiology.

7. Secondary Prevention Definition Therapy to reduce recurrent stroke and other cardiovascular events and decrease cardiovascular mortality in patients with previous stroke or TIA. Although prevention of stroke is of primary interest, many grades of recommendations were chosen to reflect the existing evidence on the reduction of all cardiovascular outcomes.

10. Components of Secondary Prevention Diuretics +/- ACE inhibitors Statins Antiplatelet agents / anticoagulants Blood pressure control Diabetes management Lipid management Smoking cessation Alcohol moderation Weight reduction / physical activity Carotid artery Interventions

11. Challenges of Dissemination The committee acknowledges that strategies for implementation of the guidelines need to be developed and disparities in health care delivery addressed.

17. Cholesterol Control ASA 2006 Secondary Stroke Recs Heart Protection Study Collaborative Group. Lancet 2002;360:7-22 Baseline feature SIMVASTATIN (10269) PLACEBO (10267) Rate ratio & 95% CI STATIN better PLACEBO better Prior coronary disease Yes No 1459 1841 (21.8%) (27.5%) 574 744 (16.1%) (20.8%) Prior cerebrovascular disease Yes 406 488 (24.7%) (29.8%) No 1627 2097 (18.9%) (24.3%) Prior diabetes Yes 601 748 (20.2%) (25.1%) No 1432 1837 (19.6%) (25.2%) ALL PATIENTS 2033 2585 (19.8%) (25.2%) 0.4 0.6 0.8 1.0 1.2 1.4 24% SE 3 reduction (2P<0.00001)

21. Urgent Endarterectomy Surgery within 2 weeks is suggested rather than delaying surgery (Class IIa, Evidence B). Rothwell PM. Lancet 2004;363(9413):915-24

24. Stroke Prevention: Non-cardioembolic ASA 2006 Recommendations For patients with noncardioembolic ischemic stroke or TIA, antiplatelet agents are recommended rather than oral anticoagulation to reduce the risk of recurrent stroke and other cardiovascular events (Class I, Evidence A).

25. Warfarin-Aspirin for Recurrent Stroke Study (WARSS) 0 90 180 270 360 450 540 630 720 Days After Randomization 0 10 20 30 Probability of Event (%) Warfarin Aspirin 1.13 Hazard Ratio P= 0.25 The primary outcome occurred in 17.8% of patients in the warfarin group and 16.0% in the ASA group. Mohr JP et al. N Engl J Med 2001;345:1444-51 900 932 951 974 984 1004 1032 1057 1103 Aspirin 885 924 939 956 972 998 1013 1047 1103 Warfarin No. at Risk

28. ESPS 2: Effects on Stroke—Relative Risk Reduction (Pair-wise Comparisons) 0.0% 5.0% 10.0% 15.0% 20.0% 25.0% 30.0% 35.0% 40.0% 37.0% P < 0.001 16.3% P = 0.039 18.1% P = 0.013 23.1% P = 0.006 ER-DP = Extended-Release Dipyridamole ASA = Acetylsalicylic Acid RRR = Relative Risk Reduction RRR ASA/ER-DP vs. Placebo ER-DP vs. Placebo ASA vs. Placebo ASA/ER-DP vs. ASA ESPS 2 Group. J Neurol Sci 1997;151(suppl):S1-S77

29. Efficacy of Clopidogrel vs Aspirin in MI, Ischemic Stroke, or Vascular Death (n=19,185) CAPRIE Study Months of Follow-up Cumulative Event Rate (%) 0 4 8 12 16 Clopidogrel Aspirin Overall Relative Risk Reduction 8.7%* 3 6 9 12 15 18 21 24 27 30 33 36 Aspirin 5.83% 5.32% Clopidogrel Event Rate per Year *ITT analysis. CAPRIE Steering Committee. Lancet 1996;348:1329-39

32. MATCH Trial Primary End Point: MI, IS, Vascular Death, or Rehospitalization for an Acute Ischemic Event Overall Relative Risk Reduction 6.4%* P = 0.244 *ITT Analysis Cumulative Event Rate Clopidogrel + ASA Clopidogrel + Placebo 0.00 0.04 0.08 0.12 0.16 0.20 0 3 6 9 12 15 18 N=7,599 Months of Follow Up Diener H-C et al. Lancet 2004;364:331-7

36. Adjusted Relative Risk of Stroke According to a Woman’s Status With Respect to Pregnancy* * Relative risks have been adjusted for age and race; † The 6-week period after pregnancy was defined as the 6 weeks after a spontaneous or induced abortion, stillbirth, or live birth; ‡ Subarachnoid hemorrhages (SAHs) have been excluded. During pregnancy or 6 weeks 1.6 (1.0-2.7) 5.6 (3.0-10.5) 2.4 (1.6-3.6) After pregnancy During pregnancy 0.7 (0.3-1.6) 2.5 (1.0-6.4) 1.1 (0.6-2.0) During 6 weeks after pregnancy 5.4 (2.9-10.0) 18.2 (8.7-38.1) 7.9 (5.0-12.7) After delivery 8.7 (4.6-16.7) 28.3 (13.0-61.4) 12.7 (7.8-20.7) After abortion 1.1 (0.2-7.9) 4.5 (0.6-33.1) 1.8 (0.4-7.2) RR of RR of RR of Cerebral Intracerebral Either Type Infarction Hemorrhage of Stroke ‡ Risk Period † (95% CI) (95% CI) (95% CI) Kittner SJ et al. (1996), N Engl J Med 335(11):768-774

37. Postmenopausal Hormones ASA 2006 Secondary Stroke Recs For women with ischemic stroke or TIA, postmenopausal hormone therapy (with estrogen with or without a progestin) is not recommended (Class III, Evidence A).

39. Estimates of Cumulative Hazards for Strokes in Women’s Health Initiative Study Time (Years) Cumulative Hazard 0.030 0.025 0.020 0 1 2 3 4 5 6 7 0.015 0.010 0.005 0 Estrogen + Progestin Placebo Rossouw et al. JAMA 2002;288(3):321-33