Stroke Prevention –What is New?

1. Stroke Prevention –What is New? Anne E. O’Duffy, MD Assistant Professor of Neurology Stroke Division Vanderbilt University Medical Center February 12, 2007

2. Vanderbilt Stroke News • JCAHO certified primary stroke center, Nov. 2005 • 4 members of the Vanderbilt Neurology Stroke Division are the only Board Certified Vascular Neurologists in the state of TN

6. Stroke Mortality

7. Stroke Subtypes

11. 61 year-old man with history of HTN, afib, prior stroke 2001, abrupt onset right hemiparesis 6:50PM while at work, global aphasia, INR 1.6 • CT outside ER: hyperdense MCA sign

13. We (Still) Must Focus on PREVENTION!

14. Stroke Prevention • Stroke, February, 2006. AHA/ASA/AAN guidelines on stroke prevention in patients with TIA and stroke • Summary with guidelines and levels of evidence • Well-referenced, single source

16. Stroke Risk and BP • UK-TIA trial BMJ313 (1996), p. 147

17. Hypertension • Commonest stroke risk factor, 50 million Americans, undertreated • HOPE suggested that ACE-I ramipril reduced stroke, MI, vascular death by 22% greater than placebo (32% reduction in stroke) • Yusef,et al NEJM 2000; 342: 145-153 • LIFE 1° stroke prevention trial in high-risk pts losartin better than atenolol • Dahlof et al Lancet 2002; 359: 995-1003

18. Hypertension • PROGRESS 2° stroke prevention in 6105 patients w/ hx stroke/TIA (irregardless of history of HTN) perindopril w/ or w/o indapamide vs placebo found 28% reduction in stroke in ‘active tx’ arm and 43% reduction w/combination therapy • Lancet, Vol. 358: September 29,2001

19. PROGRESS Results:

20. PROGRESS Results:

21. Hypertension • ALLHAT trial: 33,000 pts w/ HTN and 1 other vascular risk factor tx w/ chlorthalidone, lisinopril or amlodipine • No differences in 1° outcome measures of fatal or non-fatal MI, chlorthalidone was better than lisinopril in preventing stroke and combined vascular endpoint of stroke, MI, and PVD • Nearly 30% pts were black and thus more likely to do better w/ diuretics • JAMA, December 18,2002—Vol 288,no 23,2981-97

22. Hypertension • Specific BP agent may be less important than BP lowering for stroke prevention • The Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure—The JNC 7 Report • JAMA, May 21, 2003—Vol 289, No. 19, 2560-72

23. Lipid Lowering • Statins very effective in stroke reduction in pts w/ CAD: • 4S, CARE, LIPID trials shown 19- 28% reduction in stroke outcomes in CAD pts • SPARCL (Stroke Prevention by Aggressive Reduction in Cholesterol Levels) 2° stroke prevention, NEJM 2006; 355:549-559

24. SPARCL Results, Stroke

25. SPARCL • 4731 pts. w/cerebrovascular disease, no known CAD were randomized to 80 mg atorvastatin vs. placebo • Mean f/up 4.9 years • 16% RRR of recurrent stroke • Absolute RR 2.2%

26. Women’s Estrogen for Stroke Trial (WEST) • Randomized, double-blind, placebo-controlled trial of estrogen therapy in 664 postmenopausal women who had recently had an ischemic stroke or TIA, mean follow-up of 2.8 years • Results: Estrogen therapy did not reduce the risk of death alone, or of nonfatal stroke:

27. WEST Results

28. Women’s Health Initiative (WHI) • Defining the risks and benefits of strategies that could potentially reduce the incidence of heart disease, breast and colorectal cancer, and fractures in postmenopausal women • 16,608 women, primary outcome was CHD • Study stopped early after mean follow-up of 5.2 years based on health risks that exceeded benefits JAMA.2002;288:321-333

29. WHI Results for Stroke

30. WHI Results • HR’s for CHD 1.29, breast cancer 1.26, stroke 1.41, PE 2.13, colorectal ca 0.63, endometrial ca 0.83, hip fractures 0.66, other deaths 0.92 • Absolute excess risks per 10,000 person-yrs: 7 more CHD events, 8 more strokes (4800 total strokes/yr est.), 8 more PE’s, 8 more invasive breast ca’s • Absolute risk reductions: 6 fewer colorectal ca’s, 5 fewer hip fractures

31. Antithrombotic Therapy

34. Rate vs. Rhythm? • AFFIRM:Atrial Fibrillation Follow-up Investigation of Rhythm Management • >4000 high-risk patients w/afib • Rhythm control just as likely to suffer ischemic stroke over 3.5 yrs. as those who receive rate control alone • Warfarin reduced stroke by 68% • Presented at AAN, Honolulu, HI, PI Sherman,DG,

39. ESPRIT • Lancet 2006;367:1665-1673 • 2763 pts. w/TIA or minor stroke randomized to low dose aspirin (30-325mg) with or w/out dipyridamole • Mean f/up 3.5 years • 20% RRR in vascular death, non-fatal stroke or MI • 1% absolute RR per year

40. ESPRIT Results

43. MATCH • Management of ATherothrombosis with Clopidogrel in High-risk patients with recent TIA or ischemic stroke • Plavix + aspirin vs Plavix alone in high-risk stroke/ TIA patients (MI, DM, PVD) • 7599 pts, 500+ centers, 28 countries • 15.7% of patients taking clopidogrel + ASA had a further ischemic event vs 16.73% of patients taking clopidogrel + placebo (p=.244)

44. MATCH Results

46. MATCH Results • Life threatening bleeding 2.6 vs 1.3% P < 0.001 • Raises serious concern about use of combination anti-platelet agents in stroke patients

47. CHARISMA • NEJM 2006;354:1706-1717 • 15,603 pts. with vascular disease (27% stroke) randomized to clopidogrel vs. placebo plus aspirin • Clopidogrel no more effective than placebo in aspirin treated pts. • Increased bleeding complications with combination

48. CHARISMA Results

49. PRoFESS • Prevention Regimen For Effectively avoiding Second Strokes • 2 x 2 factorial design: Aggrenox vs. clopidogrel with or w/out Micardis (telmesartan) • N= 18,000 • Adults, >55 yrs, ischemic stroke within 90 days • Enrollment period 2 yrs, study duration 4 yrs.