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  1. Stroke:A Guidelines-Based Overview James T. DeVries, M.D., FACC, FSCAI Division of Cardiology Dartmouth-Hitchcock Medical Center Lebanon, NH

  2. Conflicts • No financial conflicts related to this talk • Off label use of products to treat ischemic stroke

  3. Outline • Background • Statistics • Stroke Prevention • Lifestyle • Hypertension • Lipids • Atrial fibrillation • Carotid disease • Anti-platelet agents • Special populations • Stroke Therapy • Pharmacologic reperfusion therapies • Mechanical reperfusion approaches • Summary

  4. Stroke Background

  5. Stroke-Symptoms/Warning Signs General Signs • Sudden numbness or weakness of the face, arm or leg, especially on one side • Sudden confusion or dizziness • Sudden trouble speaking or understanding • Sudden trouble seeing in one or both eyes • Sudden trouble walking, loss of balance or coordination • Sudden, severe headache with no known cause • Sudden trouble swallowing These symptoms often occur as TIAs

  6. TIA – Transient Ischemic Attack • TIA is a “mini stroke” that produces temporary stroke-like symptoms • TIA symptoms are the same as those of stroke • Usually only lasts for several minutes • Occurs when a blood clot temporarily clogs an artery • TIAs are extremely important predictors of stroke • In ~ 1/3 of TIA cases a person will later have a stroke ~ 50% of cases, the stroke will occur within 1 year 1. Transient Ischemic Attack, American Stroke Association, www.strokeassociation.org/, 2004.

  7. Stroke Facts • Incidence • Every 45 seconds someone in the U.S. has a stroke • Each year ~700,000 people experience a stroke. • Each year about 40,000 more women than men have a stroke • African-Americans have almost twice the risk of first-ever stroke compared to whites • Mortality • Stroke accounts for more than 1 of every 15 deaths in the U.S. • Stroke ranks No.3 among all causes of death behind heart disease and cancer • Stroke is the number one cause of adult disability in the U.S. • On average, every three minutes someone dies of a stroke 1. Heart Disease and Stroke Statistics – 2004 Update, American Heart Association, 2004, pgs 13-15.

  8. Cost of Stroke in 2007 USD • Direct costs $45 Billion • Hospital, physician, rehab • Indirect costs $20 Billion • Lost productivity • Total $65 Billion Rosamond W, Flegal K, Furie K, et al. Heart disease and stroke statistics--2008 update: a report from the American Heart Association Statistics Committee and Stroke Statistics Subcommittee. Circulation 2008;117:e25-146.

  9. Prevalence of Stroke Rosamond W, Flegal K, Furie K, et al. Heart disease and stroke statistics--2008 update: a report from the American Heart Association Statistics Committee and Stroke Statistics Subcommittee. Circulation 2008;117:e25-146.

  10. Unalterable Risks

  11. Stroke Prevention

  12. Primary and Secondary Prevention of Stroke • Tobacco abuse/obesity/inactivity • Hypertension • Lipids • Atrial fibrillation • Carotid disease • Antiplatelet therapy

  13. Estimated 10-Year Stroke Riskin 55 Year Old Adults 1 Heart Disease and Stroke Statistics – 2004 Update, American Heart Association, 2004

  14. Smoking and Stroke Gary Larsen “The Far Side”

  15. AHA-ASA Guidelines for Stroke Prevention: Lifestyle Changes Sacco RL, Adams R, Albers G, et al. Guidelines for Prevention of Stroke in Patients With Ischemic Stroke or Transient Ischemic Attack: A Statement for Healthcare Professionals From the American Heart Association/American Stroke Association Council on Stroke: Co-Sponsored by the Council on Cardiovascular Radiology and Intervention: The American Academy of Neurology affirms the value of this guideline. Stroke 2006;37:577-617.

  16. Treating Hypertension Reduces Stroke -11mm Hg SBP -4mm Hg DBP Perry HM, Jr, Davis BR, Price TR, et al. Effect of Treating Isolated Systolic Hypertension on the Risk of Developing Various Types and Subtypes of Stroke: The Systolic Hypertension in the Elderly Program (SHEP). JAMA 2000;284:465-71.

  17. Hypertension Control and Stroke Law MR, Morris JK, Wald NJ. Use of blood pressure lowering drugs in the prevention of cardiovascular disease: meta-analysis of 147 randomised trials in the context of expectations from prospective epidemiological studies. BMJ 2009;338:b1665-.

  18. Guidelines Sacco RL, Adams R, Albers G, et al. Guidelines for Prevention of Stroke in Patients With Ischemic Stroke or Transient Ischemic Attack: A Statement for Healthcare Professionals From the American Heart Association/American Stroke Association Council on Stroke: Co-Sponsored by the Council on Cardiovascular Radiology and Intervention: The American Academy of Neurology affirms the value of this guideline. Stroke 2006;37:577-617.

  19. Lipid Therapy Enrolled 4730 patients with stroke or TIA within previous 6 months and had LDL cholesterol 100-190 to high dose atorvastatin or placebo Primary outcome was first fatal or non-fatal stroke Amarenco P, Bogousslavsky J, Callahan A, 3rd, et al. High-dose atorvastatin after stroke or transient ischemic attack. N Engl J Med 2006;355:549-59.

  20. SPARCL Trial Amarenco P, Bogousslavsky J, Callahan A, 3rd, et al. High-dose atorvastatin after stroke or transient ischemic attack. N Engl J Med 2006;355:549-59.

  21. Guidelines Adams RJ, Albers G, Alberts MJ, et al. Update to the AHA/ASA recommendations for the prevention of stroke in patients with stroke and transient ischemic attack. Stroke 2008;39:1647-52

  22. Cardioembolic Disease with Atrial Fibrillation • Atrial fibrillation is a major risk factor for stroke • Using anticoagulation, when appropriate, can reduce the incidence of stroke • CHADS2 score • C Congestive heart failure 1 • H Hypertension 1 • A Age>75 1 • D Diabetes melitus 1 • S previous Stroke or TIA 2 • Score predicts risk of stroke with atrial fibrillation, in general if score 2 or greater coumadin has benefit over aspirin alone Gage BF, Waterman AD, Shannon W, Boechler M, Rich MW, Radford MJ. Validation of Clinical Classification Schemes for Predicting Stroke: Results From the National Registry of Atrial Fibrillation. JAMA 2001;285:2864-70.

  23. Stroke Risk by CHADS2 Gage BF, Waterman AD, Shannon W, Boechler M, Rich MW, Radford MJ. Validation of Clinical Classification Schemes for Predicting Stroke: Results From the National Registry of Atrial Fibrillation. JAMA 2001;285:2864-70.

  24. Randomized trial of >18,000 patients to warfarin with INR 2-3 vs. dabigatran in two dosing regiments Connolly SJ, Ezekowitz MD, Yusuf S, et al. Dabigatran versus Warfarin in Patients with Atrial Fibrillation. N Engl J Med 2009:NEJMoa0905561.

  25. Atrial Fibrillation Connolly SJ, Ezekowitz MD, Yusuf S, et al. Dabigatran versus Warfarin in Patients with Atrial Fibrillation. N Engl J Med 2009:NEJMoa0905561.

  26. The ACTIVE Investigators. Effect of Clopidogrel Added to Aspirin in Patients with Atrial Fibrillation. N Engl J Med 2009;360:2066-78.

  27. The ACTIVE Investigators. Effect of Clopidogrel Added to Aspirin in Patients with Atrial Fibrillation. N Engl J Med 2009;360:2066-78.

  28. Antiplatelet Therapy for Stroke • CAPRIE(1996) Aspirin vs. clopidogrel • ESPS-2 (1996) Aspirin vs. aspirin/dipyrimadole vs. dipyrimadole vs. placebo • MATCH (2004) Aspirin vs. aspirin+clopidogrel • ESPRIT (2006) Aspirin vs. aspirin/dipyridamole • CHARISMA (2008) Aspirin vs. aspirin+clopdogrel • PROFESS (2008) Aspirin/dipyrimadole vs. clopidogrel Bhatt DL, Fox KAA, Hacke W, et al. Clopidogrel and Aspirin versus Aspirin Alone for the Prevention of Atherothrombotic Events. N Engl J Med 2006;354:1706-17. Aspirin plus dipyridamole versus aspirin alone after cerebral ischaemia of arterial origin (ESPRIT): randomised controlled trial. The Lancet 2006;367:1665-73.

  29. Large (>20,000 patients), randomized, double blind trial • Compared two treatment strategies for preventing recurrent stroke. Primary outcome was recurrent stroke, secondary outcomes was composite of stroke, MI, or death from vascular cause. Sacco RL, Diener H-C, Yusuf S, et al. Aspirin and Extended-Release Dipyridamole versus Clopidogrel for Recurrent Stroke. N Engl J Med 2008;359:1238-51.

  30. RESULTS • No difference in primary or secondary outcomes between clopidogrel and combination of aspirin and extended release dipyridamole • Conclusion • No evidence that one strategy is superior to another in preventing recurrent stroke Sacco RL, Diener H-C, Yusuf S, et al. Aspirin and Extended-Release Dipyridamole versus Clopidogrel for Recurrent Stroke. N Engl J Med 2008;359:1238-51.

  31. Guidelines Adams RJ, Albers G, Alberts MJ, et al. Update to the AHA/ASA recommendations for the prevention of stroke in patients with stroke and transient ischemic attack. Stroke 2008;39:1647-52

  32. Special Populations • Hypercoagulable states- antiphospholipid syndromes, hyperhomocystenemia, nephrotic syndrome, malignancy, sickle cell disease • Patent foramen ovale- uncertainty about appropriate treatment (closure versus anticoagulation) • Carotid dissection- antithrombotic therapy with possible intervention • Post-MI/cardiomyopathy- role for coumadin therapy? • Oddities: CADASIL, Moyamoya, vasculitis

  33. Carotid disease:When to Treat

  34. What is Carotid Artery Disease? 20 to 30% of strokes are caused by atherosclerotic carotid artery disease1 Carotid artery disease increases the risk for stroke: • By plaque or clot breaking off from the carotid arteries and blocking a smaller artery in the brain • By narrowing of the carotid arteries due to plaque build-up • By a blood clot becoming wedged in a carotid artery narrowed by plaque Executive Committee for the Asymptomatic Carotid Atherosclerosis Study. Endarterectomy for Asymptomatic Carotid Artery Stenosis. JAMA 1995;273:1421

  35. CAROTID DISEASE • Carotid plaque most often causes symptoms due to embolization, rather than occlusion. • Extracranial carotid occlusion source of stroke in approximately 20%.

  36. Degree of Stenosis and Risk of Ipsilateral Stroke1 1. Inzitari, D. et al. N Engl J Med 2000;342:1693-1700

  37. STROKE PREVENTION • Patient subsets: • Symptomatic vs asymptomatic. • Good surgical candidates vs high risk. • Lesion subsets: • Mild, moderate, severe stenosis. • Ulcerated lesions.

  38. Asymptomatic Carotid Atherosclerosis Study (ACAS) • Objective • Determine whether addition of CEA to medical therapy can reduce the incidence of cerebral infarction in asymptomatic patients with carotid atheroscelerosis Executive Committee for the Asymptomatic Carotid Atherosclerosis Study. Endarterectomy for Asymptomatic Carotid Artery Stenosis. JAMA 1995;273:1421-1428

  39. ACAS • Age 40 - 79 years. • Asymptomatic > 60% carotid stenosis. • Surgical pts required to have angiography. • Excluded high risk of cardiac emboli.

  40. ACAS Results • 30-day stroke and death slightly higher in the CEA group: 2.3% vs. 0.4% • 1.2% stroke rate due to the pre-op angiogram • Absolute risk reduction of 5 year ipsilateral stroke was 5.9%. Executive Committee for the Asymptomatic Carotid Atherosclerosis Study. Endarterectomy for Asymptomatic Carotid Artery Stenosis. JAMA 1995;273:1421-1428

  41. Asymptomatic Carotid Stenosis • 75% stenosis: 2% - 5%/yr risk of stroke. • Ulceration increases risk of stroke. • 80% of patients with known carotid stenosis will not have warning TIA before stroke.

  42. North American Symptomatic Carotid Endarterectomy Trial (NASCET) • Evaluated the benefit of carotid endarterectomy in randomized patients who have experienced symptoms related to arteriosclerotic stenosis of the carotid artery • 659 pts with 50-99% stenosis in symptomatic carotid artery randomized to endartectomy vs medical rx. NASCET Collaborators. Beneficial Effect of Carotid Endarterectomy in Symptomatic Patients with High Grade Carotid Stenosis N Engl J Med 1991; 325:445-53

  43. NASCET Results >70% Stenosis Group • CEA had a slightly higher perioperative stroke and death rate than medical therapy. • CEA had a significantly lower 2 year ipsilateral stroke rate. An absolute risk reduction of 17%. NASCET Collaborators. Beneficial Effect of Carotid Endarterectomy in Symptomatic Patients with High Grade Carotid Stenosis N Engl J Med 1991; 325:445-53

  44. Carotid Endarterectomy SYMPTOMATIC PATIENTS p < .001 p < .001 p = .045 NASCET Collaborators. Beneficial Effect of Carotid Endarterectomy in Symptomatic Patients with High Grade Carotid Stenosis N Engl J Med 1991; 325:445-53

  45. CAROTID SURGERY INCIDENCE OF IPSILATERAL STROKE NASCET 50% - 69% ACAS > 60%

  46. Recent MI Severe CAD or VHD Poor EF Uncontrolled HTN Atrial fibrillation Contralateral occlusion Recurrent stenosis Radiation fibrosis Age > 80 years Crescendo symptoms Aoto-ostial stenosis Intracranial stenosis Patients Excluded from ACAS/NASCET

  47. ACAS and NASCET • Best Patients • Best Surgeons • Best Hospitals • “Medical therapy” consisted of aspirin enrollment vs. screened patients: NASCET 33% ACAS 4%

  48. Are we deluding ourselves?

  49. Gurm HS, Yadav JS, Fayad P, et al. Long-Term Results of Carotid Stenting versus Endarterectomy in High-Risk Patients. N Engl J Med 2008;358:1572-9.