1. UPDATE on Evaluation and Management of TIA and Stroke Claire J. Creutzfeldt UW Harborview Stroke Center January 2015

2. Outline 1.Some stroke facts 2.Approach to evaluation and management of Stroke 3.Acute management of Ischemic stroke  TIA  Stroke  Thrombectomy 4.Chronic management  Antithrombotic therapy 5.Hemorrhagic stroke 6.Time for questions

3. Stroke facts ~700,00 strokes each year in the US o a stroke every 45 seconds o 200,000 of those are recurrent strokes Kills >150,000 people/yr in US 28% of stroke victims < 65 years old 3rd most common cause of death, ranking behind diseases of the heart and cancer 4,500,000+ stroke survivors are alive in US leading cause of long-term disability in the US 4 th AHA Heart and Stroke Statistical Update 2014

4. Stroke classification Normal Ischemic Intracerebral Subarachnoid stroke hemorrhage hemorrhage (80%) (15%) (5%)

5. “A stroke happens, when… Mechanisms Causes of initial event Prevention of recurrent stroke  Large vessel arteriosclerosisCarotid endarterectomy, Antiplatelet  CardioembolismAnticoagulation  Small vessel diseaseAntiplatelet agent  Other  Cryptogenic(Antiplatelet agent) …blood flow to a part of the brain is interrupted”

6. Evaluation BASIC STROKE EVALUATION Thorough H&P Non-con head CT Imaging of extracranial arteries EKG and telemetry Routine blood studies (TTE) COMPREHENSIVE STROKE EVALUATION MRI Imaging of intra- and extracranial arteries TEE Prolonged cardiac monitoring U-tox Blood tests for hypercoagulable state Genetic tests for rare causes such as CADASIL, Fabry’s disease, MELAS…

7. Case 1 70 y/o m with h/o diabetes and hypertension presents to clinic and tells you about this episode yesterday where he couldn’t move his entire right side. Symptoms resolved within half an hour. BP 165/85, neurologically intact  What is your next step?

8. Case 1 A.Do a thorough neurological exam. If he really has no residual neurological deficits, no need for imaging B.Optimize his blood pressure management and have him follow up in a month C.Refer him to a TIA clinic (urgently), offer him admission to the hospital OR get an expedited workup yourself consisting of MRI brain, vascular imaging, EKG, Echocardiogram and blood work. D.Educate him about the difference between TIA and stroke and have him follow up in a month E.Add Clopidogrel to his daily baby Aspirin and have him follow up in a month

9. Risk of Stroke after TIA 1707 TIA patients Stroke event rates: 10.5% at 90 days 5.3% at 2 days JAMA 2000;284:2901-2906

10. ABCD 2 score for TIA Risk Stratification 5 FactorsPoints A ge > 60 1 B P > 140/90 on first assessment after TIA 1 C linical features unilateral weakness speech impairment without weakness 21 21 D uration of TIA ≥60 minutes 10–59 minutes 2121 D iabetes 1 Lancet 2007; 369: 283–92

11. ABCD 2 score Lancet 2007; 369: 283–92

12. Early TIA management Our system: offer admission to all Others: TIA clinic Treat: – Risk factors – Antithrombotics – CEA Test: – Brain imaging (CT or MRI) – Vascular imaging – Cardiac evaluation (Echo, EKG) – blood work including basics + lipids, HbA1c, others

13. Case 2 70 y/o m with h/o diabetes and hypertension presents to the ER with sudden onset R-sided numbness and weakness. BP 165/85, awake and able to walk  What is your next step?

14. Case 2 A.Refer him to a TIA clinic (urgently), offer him admission to the hospital OR get an expedited workup yourself consisting of brain and vascular imaging, EKG, Echocardiogram and blood work. B.Admit him to the stroke unit, add Clopidogrel to his daily baby Aspirin and order an MRI brain C.Thorough H&P with time of onset and NIHSS followed by stat lab draw, EKG, head CT

15. Additional History I Symptoms started one hour ago EKG: normal NIHSS 11 What medication would you want to use acutely?

16. IV tPA for Acute Ischemic Stroke Individual Patient Data Meta-analysis Lancet 2004; 363: 768-74

17. tPA inclusion/exclusion criteria IN: >18yrs, ischemic stroke w/in 3*hrs EX: * symptoms minor or rapidly improving * seizure at stroke onset * stroke or head trauma w/in 3 months * major surgery w/in 2 weeks * h/o ICH * sustained BP >185/110 (aggressive tx necessary) * GI or UT hemorrhage w/in 21 days * arterial puncture at noncompressible site w/in 7d * INR >1.7, platelets 400 3-4.5 hrs * Age >80, NIHSS >25, large stroke, ][ Lancet 2004; 363: 768-74NEJM 2008;359:1317-29.

18. What about mechanical thrombectomy?

19. Mechanical thrombectomy - a word of caution - FDA clearance was based on single-group, nonrandomized trials comparing device treatment with historical controls from PROACT II Effective recanalization but no better outcome These devices were not approved as clinically effective treatments for acute stroke but were cleared for use as devices to remove thrombus in acute stroke “Drip and ship” – method, wherein ‘smaller’ hospital starts intravenous tpa and ships the patient to a larger center for subsequent mechanical thrombectomy Circulation. 2011;123:2591-2601

20. Mechanical thrombectomy back in 2013… +2 N Engl J Med 2013;372:11-20

21. Mechanical thrombectomy fast forward to 2015… N Engl J Med 2015;372:11-20

22. Modified Rankin Scale Scores at 90 Days in the Intention-to-Treat Population. N Engl J Med 2015;372:11-20. MR CLEAN

23. What happened? ‘Old’ trials were criticized for – Use of older devices – Long interval between onset and intervention – Low recruitment rates – Did not require evidence of large vessel occlusion MR CLEAN: Thrombectomy devices in Holland were payed for exclusively in the context of the trial MR CLEAN: onset to iv tpa was much faster More results soon – ISC 2015: more trials, more subgroup analyses, more discussion

24. Additional History II Patient woke up with symptoms, last seen normal > 15 hours ago EKG: normal Symptoms: stable or progressing bbbb

25. Early supportive care Reverse ischemia (enhance perfusion) – Antithrombotic Medications – Blood Pressure – Interventions Limit injury (neuroprotection) – Glycemia (aggressively normalize) – Core body temperature Avoid infections – Glutamate antagonists – Free radical scavengers High quality care – Joint Commission Stroke Centers Stroke units Performance measures

26. Aspirin RR = 1.0 Aspirin betterPlacebo better 0.87 95% CI 0.81 to 0.94 Risk significantly reduced by 13% Doses ranged from 30 to 1500 mg per day Risk of stroke, MI, or vascular death BMJ. 2002; 324: 71–86

27. Other Antiplatelet agents Profess trial: NEJM 2008;359:1238-1251 SPS3 trial: NEJM 2012;367;817-825 SAMMPRIS trial: NEJM 2011;365:993-1003

28. A brief look at Anticoagulation Warfarin vs. Aspirin in Afib: SPAF studies N Engl J Med 1990; 323:1505-1511 Warfarin vs. Aspirin for Intracranial stenosis: WASID N Engl J Med 2005; 352:1305-1316 Warfarin vs Aspirin + Clopidogrel in Afib: ACTIVE W Stroke. 2008;39:1482-1486 Warfarin in Congestive Heart Failure: WARCEF N Engl J Med 2012; 366:1859-1869 The Newer Anticoagulants

29. Case 3 70 y/o m comes to your clinic as a hospital follow up after an ischemic stroke. PMH: Diabetes, borderline hypertension, smoking Exam today: BP 135/69, mild right-sided weakness and occasional word finding difficulties. He also seems withdrawn and depressed. Medications: ASA 81, Niacin, HCTZ 25, Insulin sq  What is your next step?

30. Case 3 A.Change Niacin to a Statin B.Change HCTZ to Chlorthalidone C.Educate patient on life-style change, diet and smoking cessation D.Consider an SSRI E.All of the above

31. Case 4 A 65 y/o woman with known hypertension had complained to her husband about a severe headache shortly before she collapsed. In the ER, she has decreased LOC, right-sided hemiparesis and aphasia. Initial BP is 230/120

32. Case 4 - CT

33. Case 4 What is the most likely etiology of her hemorrhage? A.Cerebral amyloid angiopathy B.Hypertension C.Ischemic stroke turned hemorrhagic

34. Amyloid Angiopathy ICH Hypertensive ICH Intraparenchymal hemorrhage

35. Goals of ICH therapy Prevent hematoma enlargement Blood pressure treatment Hemostatic agents Surgery Limit injury (neuroprotection) – Reduce Raised ICP – Glycemic control – Temperature Prevent Complications – Swallow screening, DVT prophylaxis, Seizure prophylaxis

36. Hematoma Expansion Prevent hematoma enlargement/Reduce ICP -Blood pressure treatment (goals, agents) -Hemostatic agents -Surgery

37. Stroke complications Semin Neurol. 2010

38. Thank you