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Intra - Arterial Thrombolysis for acute stroke

Intra - Arterial Thrombolysis for acute stroke . Jeanne Teitelbaum md Associate Professor Neurology and Critical Care. Intra - Arterial Thrombolysis. Effect on recanalisation Effect on clinical outcome Risks ?? Indications. Why consider IAT. IV rt-PA: Limited to < 3H

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Intra - Arterial Thrombolysis for acute stroke

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  1. Intra - Arterial Thrombolysisfor acute stroke Jeanne Teitelbaum md Associate Professor Neurology and Critical Care

  2. Intra - Arterial Thrombolysis • Effect on recanalisation • Effect on clinical outcome • Risks • ?? Indications

  3. Why consider IAT • IV rt-PA: • Limited to < 3H • Clear but limited clinical benefit • Rate of recanalisation (doppler): • Complete: 32% • Partial or none 68%: 67% MCA, 25% BA, no ICA (Christou et al 2001)

  4. Why consider IAT • Persistent obstruction persistent deficit • Increase the therapeutic window • Post-operative stroke • Reduce hemorrhagic complications

  5. I.A.T. Theoretical Advantages • Higher concentrations delivered to the clot • Gentle mechanical disruption of the clot • Precise imaging of anatomy, pathology and collateral pattern • Exact degree and timing of recanalisation

  6. I.A.T. Potential Disadvantages • Catheter manipulation • Systemic heparinisation • Delay in initiation of thrombolysis • Skilled facilities

  7. Intra-arterial Thrombolysis The Evidence

  8. Anterior Circulation

  9. PROACT II Trial • First phase III trial of I.A.T. • Pro-UK + heparin vs IV heparin within 6h. • 180 patients, M1 or M2 MCA occlusion. • Average NIHSS 17. • Median time to I.A.T 5.7 hours.

  10. PROACT II Trial • mRS < 2 : 40% VS 25% (+- SIG) • Recanalisation at 2h: 66% vs 18% • Hemorrhage at 36h: • all: 46% vs 16% • symptomatic: 10% vs 2% • No difference in mortality

  11. I.A.T. Rate of RecanalisationDepends on site and type of occlusion • PROACT II :66% overall • Urbach et al 2002: Thrombus 53%: 23% carotid T, 74% distal M1 60% M2

  12. I.A.T. Rate of RecanalisationDepends on site and type of occlusion • Urbach et al 2002: • Embolus 59% overall 1of 6 with cardiac thrombus 15 of 19 (79%) without thrombus

  13. I.A.T. Therapeutic Window • PROACT II: 6h • Arnold et al stroke 2002: 100 pts • Urokinase, MCA, NIH = 14 • Average 236 minutes • Recanalisation: 76% • Outcome: excellent 47%, good 21%, poor 22%, dead 10%, hemorrhage 7%

  14. I.A.T. Therapeutic Window • Evidence that TTT influences outcome • New studies in progress: 1.5 to 6 h.

  15. MRI data Kidwell et al • Ann Neurol 2000 • 7 patients • DWI and PWI pre and post I.A.L. • DWI 3 and 9 h post recanalisation • delayed re of DWI at 7 days • Final volume 86% of original pre - lysis

  16. IV plus IA thrombolysisStroke Bridging Trial • Lewandowski CA et al Stroke 1999 • Randomized pilot study. 35 patients • tPA IV 0.6 mg/Kg then IA 20 mg • Symptomatic hemorrhage: 11% both groups • Recanalisation at 2h: • All: 55% IV/IA vs 10% IA • M1: 100% IV/IA vs 67% (PROACT)

  17. IV plus IA ThrombolysisErnst et al Stroke 2000 • Continuation of the bridging trial • 20 patients • Anterior circulation CVA, NIHSS > 10, planned tPA within 3H • Same dose and method of administration

  18. IV plus IA ThrombolysisErnst et al Stroke 2000 • Results: • Initial NIHSS: 11 to 31 (median 21) • IV tPA: median 2H (1H12min to 4H 10 min) • IA tPA: median 3H 30 min

  19. IV plus IA ThrombolysisErnst et al Stroke 2000 • Recanalisation: 69% • Heparin bolus in 11patients, infusion in 7 • 4 hemorrhages, 1 sympt • 10 of 16 patients mRS 0-2. • No change in 90d mortality

  20. IV plus IA ThrombolysisZaidat et al Stroke 2002 • 207 pts thrombolysed from 1995-2000 • IA or IV + IA • 101 had angio • 18 ipsilateral distal ICA occlusion

  21. IV plus IA ThrombolysisZaidat et al Stroke 2002 • No difference between groups for: • Recanalisation (70%) • Outcome: mRS 0-2 77% in survivors • Sympt hemorrhage (15-20%) • Mortality: 50% !!

  22. I.A.T. Post-Operative Period • Chalela et al, Stroke 2001 • Retrospective, median time to stroke 21h • Median TTT: 4.5h (1 to 8h) • tPA or UK • 36 patients, 3 major bleeds, 2 post craniotomy, all fatal Minor bleed 25%

  23. Posterior Circulation

  24. Vertebrobasilar Thrombosis • Life-threatening event: mortality 75-86% • No effective therapy • Heparin: accepted but unproven • Some authors reporting success with IAT: • Retrospective • Small groups

  25. Vertebrobasilar I.A.T. • Time frame: 1 to 48 h after last progression • Most patients present 24-48 h after onset • Only 3 studies with > 10 patients

  26. Vertebrobasilar I.A.T. • Cohort mortality is decreased compared to historic controls when successful thrombolysis has been achieved. • Benefit even 24 h after presentation.

  27. Vertebrobasilar I.A.T.4 major series • Average time to therapy: up to 24h • Mortality: 46%, 54%, 67%, 75% • Recanalization: 75%, 71%, 54%, 75% • Hemorrhage: 7%, 0%, 9%, 15% • Rethrombosis: --- 10%, --- 30% • Recanalized mortality: 26% to 30%

  28. Vertebrobasilar I.A.T.Factors affecting outcome • Infarction of a critical amount of brainstem tissue • Coma and quadriparesis at presentation • Lack of recanalization, rethrombosis

  29. Possible Conclusions

  30. I.A.T. Anterior Circulation • The lack of recanalization is linked to poor outcome. • Better rate of recanalization: 70 vs 34%. • Likely better effect on outcome than IV tPA • Larger therapeutic window (6h), • Can be given post-operatively (except post craniotomy)

  31. I.A.T. Anterior Circulation • Combined IV-IA: may be as good or better than IA alone. Can be started faster. • Hemorrhage rates 7 – 10% • Drawbacks: technique, time to initiation, dose variation.

  32. I.A.T. Vertebrobasilar system • No satisfactory studies. • Very grim prognosis • I.A.T. only life-saving therapy available • Beneficial effect on mortality and morbidity with recanalization

  33. I.A.T. Vertebrobasilar system • Up to 24h after deterioration, up to 48h after onset. • Less benefit if coma, quadriparesis, large area of infarct pre-treatment.

  34. ?? Indications

  35. Indications in Anterior Circulation • Persistent occlusion post IV tPA < 3h • Within 6 h, but time to treatment is correlated with outcome. • IV contra-indicated with evidence of viable tissue: post-op, > 3H • tPA 9 to 40 mg (med 21) • UK 40,000 – 1,500,000 (med 500,000)

  36. Indications in Posterior Circulation • Worsening symptomatology despite heparin • Visualized occlusion • Up to 24h after onset of worsening • UK 250,000-500,000 per H x 2 then 250,000u per H x 4. With heparin. • tPA: less well studied.

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