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Stroke Prevention –What is New?

Stroke Prevention –What is New?. Anne E. O’Duffy, MD Assistant Professor of Neurology Stroke Division Vanderbilt University Medical Center February 12, 2007. Vanderbilt Stroke News . JCAHO certified primary stroke center, Nov. 2005

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Stroke Prevention –What is New?

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  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

  3. Stroke Mortality

  4. Stroke Subtypes

  5. 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

  6. We (Still) Must Focus on PREVENTION!

  7. 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

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

  9. 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

  10. 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

  11. PROGRESS Results:

  12. PROGRESS Results:

  13. 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

  14. 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

  15. 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

  16. SPARCL Results, Stroke

  17. 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%

  18. 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:

  19. WEST Results

  20. 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

  21. WHI Results for Stroke

  22. 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

  23. Antithrombotic Therapy

  24. 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,

  25. 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

  26. ESPRIT Results

  27. 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)

  28. MATCH Results

  29. 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

  30. 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

  31. CHARISMA Results

  32. 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.

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