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Acute Stroke The Present and the Future… Andrew Woolfenden MD, FRCPC Stroke Neurology Assistant Professor University of British Columbia UBC
Disclosure Slide ,[object Object],[object Object],[object Object]
Objectives ,[object Object],[object Object],[object Object]
The Vancouver General Hospital Stroke Team ,[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object]
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
Acute Ischemic Stroke ,[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],To date, reperfusion is the only successful strategy…
Intravenous t-PA in Acute Stroke  The NINDS Trials NEJM 1995.333:1581-7
CASES NINDS data from Combined A & B NINDS rtPA Stroke Trial
CASES Adverse Events ,[object Object],[object Object],[object Object],[object Object],[object Object]
 
Number Needed to Treat Increases Exponentially with Time NNT = 4 at 90 minutes
Thrombolysis in Acute Stroke Pooled Analysis 4h 40 min
Thrombolysis in Acute Stroke “ If it wasn’t for the last minute, nothing would ever get done!” Human nature? VGH tPA Experience Stroke 2000
BC CASES   Mean Interval Times ,[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],N = 185
ERP + Acute Stroke ,[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object]
tPA Availability ,[object Object]
tPA… Moving Forward… ,[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object]
Selection of patients using imaging Perfusion Imaging
Novel Thrombolytics ,[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object]
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 ,[object Object],[object Object],[object Object],[object Object],[object Object],[object Object]
Intra-arterial Thrombolysis ,[object Object],[object Object],[object Object],Options 1. IV tPA 2. IA tPA 3. Prayer 4. All of the above!
Interventional Management of Stroke - IMS III ,[object Object],[object Object],[object Object],[object Object],[object Object]
Neuroprotection Again ? ,[object Object]
ICH
ICH Pathophysiology Early hematoma expansion 2.0 hours after onset 6.5 hours after onset ,[object Object],[object Object],[object Object]
ICH Management Surgery ,[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],Lancet 2005;365:387-97
 
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
ICH Management Factor VIIa ,[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],0 2 hrs 3 hrs 1 hr Onset-to-CT CT-to-Needle
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
ICH Management Factor VIIa p=0.02 p=0.02, Chi Square test p=0.10 Log rank test PLACEBO 18% 29% Mortality
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
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
? Day 89
Other Effective Stroke Therapies ,[object Object],[object Object]
Acute Stroke Summary ,[object Object],[object Object],[object Object],[object Object]
The End…
Questions?

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Acute Stroke Management Handouts Power Point885

  • 1. Acute Stroke The Present and the Future… Andrew Woolfenden MD, FRCPC Stroke Neurology Assistant Professor University of British Columbia UBC
  • 2.
  • 3.
  • 4.
  • 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.
  • 7. Intravenous t-PA in Acute Stroke The NINDS Trials NEJM 1995.333:1581-7
  • 8. CASES NINDS data from Combined A & B NINDS rtPA Stroke Trial
  • 9.
  • 10.  
  • 11. Number Needed to Treat Increases Exponentially with Time NNT = 4 at 90 minutes
  • 12. Thrombolysis in Acute Stroke Pooled Analysis 4h 40 min
  • 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
  • 14.
  • 15.
  • 16.
  • 17.
  • 18. Selection of patients using imaging Perfusion Imaging
  • 19.
  • 20.
  • 21.
  • 22.
  • 23.
  • 24. ICH
  • 25.
  • 26.
  • 27.  
  • 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
  • 29.
  • 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
  • 31. ICH Management Factor VIIa p=0.02 p=0.02, Chi Square test p=0.10 Log rank test PLACEBO 18% 29% Mortality
  • 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
  • 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
  • 35.
  • 36.