Thrombolytic Therapy For Acute Stroke

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Thrombolytic Therapy For Acute Stroke

  1. 1. Stroke is a major problem. 730,000 strokes / yr in USA → one every 45 seconds Third leading cause of death Thrombolytic Therapy for Acute Stroke: Intravenous, Number one cause of major disability Intrarterial or both? Significant burden to society: ~ $50 billion/yr Growing elderly population → pending epidemic? Leading causes of world deaths in 2005 Stroke – past Cause No of deaths All cardiovascular 17.5 million • Ischemic heart disease 7.6 million • Cerebrovascular disease 5.7 million All cancer 7.6 million • Lung cancer 1.3 million • Stomach cancer 1 million • Liver cancer 662 000 • Colon cancer 655 000 • Breast cancer 502 000 Source: World Health Organization Stroke – present Stroke – present good outcome with IV tPA(mRS 0-1): 39% vs. 26% 1 IV tPA exclusions / contraindications most patients arrive too late (>3 hrs for NINDS) 1. > 3 hrs from stroke onset 2. 80 > age > 18 currently, only 0.6-1.8% of strokes get IV tPA 2,3 0.6- 3. pregnancy (up to 10 days postpartum) 4. “symptoms suggestive of SAH” – despite negative CT 5. “rapidly improving or minor symptoms” 6. “seizure at onset of stroke” 7. ever: → history of intracranial hemorrhage 8. within 3 mo: → stroke, serious head trauma, intracranial surgery Odds Ratio for Favorable Outcome 9. within 21d: → GI/urinary/pulmonary hemorrhage 10. within 14d: → major surgery 11. within 7d: → arterial puncture at a non-compressible site 12. SBP > 185 mmHg or DBP > 110 mmHg 13. aggressive treatment required to reduce BP to specified limits 14. current use of anticoagulants (or recent, with PT > 15s) 15. use of heparin within 48hrs and elevated PTT 16. platelets < 100,000 17. glucose < 50 or > 400 mg per deciliter 18. brain tumour, abscess, aneurysm, AVM 19. bacterial endocarditis 20. known bleeding diathesis – includes renal, hepatic insufficiency 21. etc… NINDS NEJM 19951, Katzan JAMA 20002, Qureshi NRS 20053 1
  2. 2. Stroke – present Stroke – present IV tPA is less effective for severe strokes 1 85% of strokes are ischemic NIHSS ≥ 10: 75% decreased chance of good outcome 70% are non-lacunar strokes NIHSS > 20: only 8% will attain NIHSS=1 after IV tPA 36% arrive 0-3h and 21% 3-6h1 60%-83% of strokes have a NIH Stroke Score ≥ IV tPA is less effective for large vessel occlusions 2,3 102,3 ICA recanalization rate is 1/3 that of MCA tandem ICA/MCA has poor recanalization & bad prognosis Only 0.6-2% of strokes receive IV tPA; 0.07% received IA tPA with higher use in larger IV tPA is relatively slow-acting 4,5 slow- hospitals, even though 21% arrive 0-3h and TCD over 6hrs → 30% recan (of which ¾ are within 1hr tpa) tpa) 11% 3-6h4,5 angio 1hr after tPA → 1/10 ICA/proximal MCA, 1/3 distal MCA 1: NINDS Stroke 1997; 28:2119–2125 2: LInfante Stroke 2002; 33:2066-2071 33:2066- 3: Rubiera Stroke 2006; 37:2301-2305 37:2301- Zweifler Neurology 19981, NINDS NEJM 19982, Alexandrov NEJM 20043 Katzan JAMA 20004, Qureshi NRS 20055 4: Christou Stroke 2000; 31:1812-1816 31:1812- 2000 , 2005 5: Lee Stroke 2007; 38:192-3 vs vs Stroke. 2007 Jan.38(1).192-3 Stroke. 2007 Jan.38(1).192-3 “Time is brain” Stroke – future? typical supratentorial large vessel stroke: ~54ml brain is Extended Time Window up to 8+ hrs – depending on lost over ~10 hrs individual perfusion Applicable in patient’s with contra-indications to IV rTPA patient’ contra- per hour: 830 billion synapses, 120 million neurons, 447 Recent surgery or anticoagulation miles of myelinated fibre lost 75% decreased odds of good recovery with NIH>10 with IV1 each hour, brain effectively ages 3.6 years hour, PROACT II2 patients had a 15% absolute benefit versus controls (40% vs. 25%, p=0.04) The recanalization rate was 66% with IA r-proUK compared Saver, Stroke 2006; 37:263 to ~30% with IV tPA3 PRESUMPTIONS: for patients with NIHSS > 10 IA therapy will be superior to IV tPA More patients will have access to thrombolytic therapy Stars Jama 20001, Furlan Jama 20012 ,Demchuk Stroke 2001 3, 2
  3. 3. Stroke – future? now. Stroke – new tools Thrombolytics: → Alteplase, Retavase Treatment of Acute MI GIIb/IIIa inhibitors: → Reopro, Integrilin 1987 1993 2000 2003 IV tPA PTCA Stent Cypher Mechanical disruption: → microwire / snare Clot retrieval: → MERCI, Penumbra Treatment of Acute Stroke Ultrasound Catheter: → EKOS 1996 1999 2004 today ??? Angioplasty / Stenting → Gateway / Wingspan IV tPA PROACT II MERCI Retriever Multimodal Revascularization Concentric Retriever System Angioplasty / Stent Lessons From the Heart? Maverick® OTW Balloon Catheter (Boston Scientific) Useful for underlying atheroma Occlusions refractory to reopening with other means Thrombus Retriever Consider stenting to restore flow early Wingspan Stent (Boston Scientific) 9 Fr Balloon Guide Catheter Intracranial Stenting Case example: 45 yo male acute LMCA stroke R paretic, R hemianopic, R facial droop, dysphasic, dysarthric. NIHSS = 15 Gateway/Wingspan (Boston Scientific) 3
  4. 4. LCCA origin severe stenosis, 5F sim2 finally pops in but is occlusive (static dye column) T-occlusion equivalent: proximal LA1, LM1 occluded, poor collateralization All-star 0.014 wire maintains access to LCCA, pigtail arch run shows severe origin stenosis Cross LM1 occlusion with MERIC 18L microcatheter over transend AP Lateral 1. Aviator 6x30mm over All-star wire, LCCA origin angioplastied 2. Sim2 back over All- star wire into distal LECA 3. All-star wire then exchanged for 0.035 stiff exchange glidewire 4. Sim2 swapped out for 7F concentric balloon guide over stiff exchange wire, parked in LCCA 5. Concentric guide catheter taken to distal cervical LICA 6. LMCA occlusion crossed with 18L Concentric microcatheter over Transend microwire… Deploy MERCI L5 retriever Clot retreived, flow restored AP Lateral AP Lateral 4
  5. 5. Pre AP AP Lateral Post Post – Arch MRA: LCCA stenosis better, inominate as before, will need tx later 5
  6. 6. - 38 yo female: acute left hemisphere stroke (aphasia, hemiplegia) - CT stroke protocol in ED → IV tPA given, endovascular team assembled - findings: large area of ischemic but salvageable brain, left MCA occlusion blood flow blood volume - 38 yo female: acute left hemisphere stroke (aphasia, hemiplegia) - CT stroke protocol in ED → IV tPA given, endovascular team assembled - findings: large area of ischemic but salvageable brain, left MCA occlusion - result: Merci clot retrieval... 85 yo female RMCA stroke onset >7 hrs NIHSS=19 CBV CBF MTT 6
  7. 7. Pre Postop Day #1 MRI – NIHSS now 2 Stroke Algorithm Acute Stroke CTA / CTP 0-3 hr >3 hr large vessel occl. (ICA, M1/M2, A1, VA/BA) large vessel occl. (ICA, M1/M2, A1,VA/BA) large ischemic penumbra > infarct large ischemic penumbra > infarct large stroke (NIHSS≥8) large stroke (NIHSS≥8) yes no yes no IA Tx ± bridging IV tPA IV tPA IA Tx no acute thrombolysis, later medical or surgical stroke prophylaxis 7

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