1. Acute Stroke The Present and the Future… Andrew Woolfenden MD, FRCPC Stroke Neurology Assistant Professor University of British Columbia UBC

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

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

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

18. Selection of patients using imaging Perfusion Imaging

24. ICH

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

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

34. ? Day 89

37. The End…

38. Questions?