Acute Stroke Management Handouts Power Point885

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  • Acute Stroke Management Handouts Power Point885

    1. 1. Acute Stroke The Present and the Future… Andrew Woolfenden MD, FRCPC Stroke Neurology Assistant Professor University of British Columbia UBC
    2. 2. Disclosure Slide <ul><li>CME Honorarium: Sanofi, BI, Dupont, Roche, Aventis, Servier, Merck, NovoNordisk, Glaxo, Pfizer, Allergan, UBC, CSC </li></ul><ul><li>Advisory Board: Dupont, Sanofi, BI, NovoNordisk, Endovasix, Glaxo, Merck </li></ul><ul><li>I own no stock in pharmaceutical companies </li></ul>
    3. 3. Objectives <ul><li>Highlight the importance of time in the administration of IV thrombolysis </li></ul><ul><li>Discuss new insights concerning IV and IA thrombolysis </li></ul><ul><li>Overview the future of interventional ischemic stroke therapy </li></ul>
    4. 4. The Vancouver General Hospital Stroke Team <ul><li>Neurologists </li></ul><ul><li>Stroke Study Nurses </li></ul><ul><li>Neurology Residents </li></ul><ul><li>Neuroradiology </li></ul><ul><li>Neurosurgery </li></ul><ul><li>Local Feeder Hospitals + VGH ER </li></ul><ul><li>EHS </li></ul><ul><li>Stroke Pager </li></ul>
    5. 5. Outcome of Stroke Adapted from Stegmayr B, et al. Stroke 1997;28:1367-1374 About 50% are either dead or disabled Prognosis of ICH worse than IS
    6. 6. Acute Ischemic Stroke <ul><li>80% of patients with an </li></ul><ul><li>acute ischemic stroke </li></ul><ul><li>have clot on angio within </li></ul><ul><li>6 hours of stroke onset </li></ul><ul><li>An NIHSS of > 10 is </li></ul><ul><li>predictive of the presence </li></ul><ul><li>of clot on angio </li></ul>To date, reperfusion is the only successful strategy…
    7. 7. Intravenous t-PA in Acute Stroke The NINDS Trials NEJM 1995.333:1581-7
    8. 8. CASES NINDS data from Combined A & B NINDS rtPA Stroke Trial
    9. 9. CASES Adverse Events <ul><li>52 symptomatic ICH </li></ul><ul><ul><li>4.6% (95% CI = 3.4 to 5.9) </li></ul></ul><ul><ul><li>81% 90-day mortality with sICH </li></ul></ul><ul><li>15 anaphylactoid/angioedema reactions </li></ul><ul><ul><li>1.3% (95% CI 0.7 to 2.2) </li></ul></ul>
    10. 11. Number Needed to Treat Increases Exponentially with Time NNT = 4 at 90 minutes
    11. 12. Thrombolysis in Acute Stroke Pooled Analysis 4h 40 min
    12. 13. Thrombolysis in Acute Stroke “ If it wasn’t for the last minute, nothing would ever get done!” Human nature? VGH tPA Experience Stroke 2000
    13. 14. BC CASES Mean Interval Times <ul><li>Canada BC </li></ul><ul><li>Onset-ER 68 min 58 min* </li></ul><ul><li>ER-CT 41 min 58 min* </li></ul><ul><li>CT-Needle 51 min 47 min </li></ul><ul><li>Door-Needle 87 min 102 min* </li></ul><ul><li>ONSET-NEEDLE 150 min 150 min </li></ul><ul><li>*p<0.05 2-sample t-test </li></ul>N = 185
    14. 15. ERP + Acute Stroke <ul><li>Confirm it’s a stroke </li></ul><ul><li>Time of onset </li></ul><ul><ul><li>Witnessed </li></ul></ul><ul><ul><li>Last known to be well </li></ul></ul><ul><li>Examination </li></ul><ul><ul><li>BP, HR </li></ul></ul><ul><ul><li>Speech, gaze palsy, (visual fields), paralysis and severity </li></ul></ul><ul><li>Initiate labs </li></ul><ul><ul><li>CBC, glucose, creatinine, INR, PTT </li></ul></ul><ul><li>(Arrange CT) </li></ul><ul><li>Initiate neurology contact </li></ul><ul><li>VGH stroke pager </li></ul><ul><li>707-3030 </li></ul>
    15. 16. tPA Availability <ul><li>Most Canadian Stroke Centers treat 10-20% of all strokes with tPA </li></ul>
    16. 17. tPA… Moving Forward… <ul><li>Better pre-hospital organization </li></ul><ul><li>More widespread access </li></ul><ul><ul><li>Non-neurologists, telemedicine </li></ul></ul><ul><li>Advanced thrombolytics </li></ul><ul><li>Safer thrombolytics </li></ul><ul><li>Improved patient selection </li></ul><ul><li>Alternate modalities </li></ul>
    17. 18. Selection of patients using imaging Perfusion Imaging
    18. 19. Novel Thrombolytics <ul><li>DIAS II </li></ul><ul><ul><li>Desmoteplase </li></ul></ul><ul><ul><li>3-9 hours </li></ul></ul><ul><ul><li>20% mismatch </li></ul></ul><ul><li>Vernalis </li></ul><ul><ul><li>3-9 hours </li></ul></ul><ul><ul><li>Altered plasminogen activated by thrombin </li></ul></ul><ul><ul><li>Imaging selection with CT/CTA </li></ul></ul>
    19. 20. D iffusion weighted imaging E valuation F or U nderstanding S troke E volution 6 cc +4:32 hrs NIH 5 65 cc ↓ M2 Flow Improved 0 cc 3 cc 5:48 NIH 16 <ul><li>DWI/PWI mismatch identifies potential tPA responders; </li></ul><ul><li>matched lesions do not benefit from reperfusion </li></ul><ul><li>Malignant MRI pattern predicts irreversible injury and </li></ul><ul><li>reperfusion leads to severe ICH </li></ul><ul><li>Small baseline DWI and PWI lesions associated with </li></ul><ul><li>favorable outcomes </li></ul>
    20. 21. Intra-arterial Thrombolysis <ul><li>45 minutes post R MCA stroke </li></ul><ul><li>NIHSS 21 </li></ul><ul><li>If it were you, what treatment would you want?? </li></ul>Options 1. IV tPA 2. IA tPA 3. Prayer 4. All of the above!
    21. 22. Interventional Management of Stroke - IMS III <ul><li>IMS I + II Trial IV tPA IMS I IMS II </li></ul><ul><ul><li>IV/IA Rankin 0-2 39% 43% 45% </li></ul></ul><ul><ul><li>ICH 6.3-11% </li></ul></ul><ul><li>IMS III </li></ul><ul><ul><li>IV vs IV/IA vs IV/MERCI </li></ul></ul>
    22. 23. Neuroprotection Again ? <ul><li>SAINT I </li></ul>
    23. 24. ICH
    24. 25. ICH Pathophysiology Early hematoma expansion 2.0 hours after onset 6.5 hours after onset <ul><li>Contiuned arterial bleeding </li></ul><ul><li>Secondary bleeding into perilesional tissue </li></ul><ul><li>Subsequent perilesional edema </li></ul>
    25. 26. ICH Management Surgery <ul><li>1033 patients most within 24 hours </li></ul><ul><ul><li>>25% cross-over </li></ul></ul><ul><ul><li>75% craniotomy, 25% endoscopic </li></ul></ul><ul><li>GCS 5-8, poorer outcome with surgery: OR 1.93 </li></ul><ul><li>Craniotomy had better outcome than other methods of clot extraction </li></ul><ul><li>ICH ≤ 1 cm of cortical surface had better outcome from surgery: OR 0.69 versus OR 1.39 </li></ul>Lancet 2005;365:387-97
    26. 28. ICH Management Active Medical Treatment NovoSeven ® directly activates factor X on the surface of the locally activated platelets Hoffman, M, et al. Thromb Haemost 2001;85:958. t ½ = 2.6 hrs INITIATION : Tissue Factor/FVIIa interaction leads to thrombin generation AMPLIFICATION : rFVIIa activates factor X on the surface of activated platelets, leading to an enhanced thrombin burst at the site of injury FIBRIN CLOT FORMATION: Thrombin converts fibrinogen into fibrin, producing a stable clot
    27. 29. ICH Management Factor VIIa <ul><li>400 patients randomized (Aug 02 - June 04) </li></ul><ul><ul><li>Intention-to-treat population = 399 </li></ul></ul><ul><ul><ul><li>One patient withdrew consent </li></ul></ul></ul><ul><li>Treatment Intervals </li></ul><ul><ul><li>Mean onset-to-CT interval 114 ± 35 min </li></ul></ul><ul><ul><li>Mean CT-to-Needle interval 54 ± 21 min </li></ul></ul><ul><ul><li>Mean onset-to-needle interval 167 ± 32 min </li></ul></ul>0 2 hrs 3 hrs 1 hr Onset-to-CT CT-to-Needle
    28. 30. Benefit of FVIIa is dose dependent ICH Volume Edema Volume ICH + IVH + Edema Volume • P<0.05 •• P<0.01 ••• P<0.005 • ••• ••• •• • ••• Absolute change in lesion volume compared to placebo (mL) p = 0.02 for trend
    29. 31. ICH Management Factor VIIa p=0.02 p=0.02, Chi Square test p=0.10 Log rank test PLACEBO 18% 29% Mortality
    30. 32. Patient Outcome with FVIIa Outcome Pl 40 80 160 NNT 7.1 5.0 6.7 ARR 16%, p = 0.004 (group) 54% P=0.023 49% P=0.008 55% P=0.018 69% mRS 4-6 0.14 73% 81% E-GOS 0.008 6.0 12.5 NIHSS 0.006 60.0 25.0 BI 0.004 53% 69% mRS 0.02 18% 29% Death P value Total Rx Placebo Variable
    31. 33. ICH Management Active Medical Treatment Factor VIIa Frequency of Thrombo-Embolic SAEs * Fisher’s Exact test Arterial events significant : 7 AMI, 7 AIS (3% early, 5% total) Venous events non-significant : 3 PE Total Thromboembolic Events Total: 7% treatment; 2% placebo Serious: 2% treatment; 2% placebo 0.12 10% 4% 6% 2% P-value* 160 µg/kg 80 µg/kg 40 µg/kg Placebo
    32. 34. ? Day 89
    33. 35. Other Effective Stroke Therapies <ul><li>ASA within 48 hours – ARR 1% </li></ul><ul><li>Stroke Units – ARR 5% </li></ul>
    34. 36. Acute Stroke Summary <ul><li>IV tPA is the standard of care </li></ul><ul><li>Future directions </li></ul><ul><ul><li>Increase utilization, improve safety, novel thrombolytics, alternate modalities </li></ul></ul><ul><li>A treatment for spontaneous ICH looms on the horizon </li></ul>
    35. 37. The End…
    36. 38. Questions?

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