Update on the acute treatment of stroke – patient selection and reperfusion therapy Andrew M. Demchuk MD FRCPC Director, Calgary Stroke Program AI-HS Scholar Heart and Stroke Foundation Chair in Stroke Research Professor, Dept of Clinical Neurosciences, Dept of Radiology University of Calgary 1
Disclosure Slide • I have not received an honorarium from Hoffman LaRoche (licensure of tPA) but have received honorarium from Covidien (supplier of SOLITAIRE FR stentriever) in the past 3 years • IMS-3- Exec committee, CT core lab PI • ESCAPE- Neuro-PI • REVASCAT- CT core lab co-PI • CLOTBUST-ER – CTA substudy PI • ARGIS-2 – CTA substudy core lab PI • ENCHANTED – International Advisory Committee • I have no stocks or direct investments with pharmaceutical or device companies involved in stroke
Stroke is multiple diseases with multiple causes Ischemic stroke ICH SAH Venous sinus thrombosis 85% 9% 5% 1%
Efficiency/Coordination Really Matters in Stroke Acute TIA/minor stroke – hours URGENCY Hyperacute disabling stroke – minutes EMERGENCY
Minor Cerebrovascular Syndrome Coull et al. BMJ 2004
Most Neuro Spells are TNAs Transient Neurologic Attacks Non-ischemic ischemic
TIA Risk Stratification: Clinical Benign/low risk Intermediate risk Malignant/high risk months weeks days hours minutes Timing since event age BP in ED/clinic DM/glucose symptoms dizziness/vertigo sensory blurry curtain speech weakness duration seconds few min 10-60 min >60 min persisting frequency
Transcranial Doppler Active embolization Probe Left MCA LACA RACA Ultrasound Beam Axis
CT-angio arch/vertex perfect for highr risk TIA Protruding aortic plaque Terminal ICA stenosis iNOT Aortic dissection Carotid stenosis Carotid ILT MCA occlusion Basilar stenosis Aortic thrombus Basilar stenosis
140 ml 68 ml 41 ml 34 ml 8 ml
Proportion mortality independent outcome 140 ml 68 ml 41 ml 34 ml 8 ml
Intracerebral Hemorrhage
68 ml 8 ml
Craniotomy-evacuation Minimally invasive surgery Endoscope +/- tPA
Earlier surgical evacuation of the haematoma in selected patients with spontaneous lobar ICH vs initial conservative tx. 600 patients Outcome at six months Final Results: European Stroke Conference May 2013
“Early Hematoma Growth” One in Three DRIP in front of our eyes 6.5 hours after onset, with 2.5 hours after enlargement of the hematoma symptom onset due to ongoing bleeding
41 ml 34 ml 8 ml time
n=2800 enrollment complete Results May 2013
CTA Spot Sign + rFVIIa trials
Ischemic Stroke
Peri-infarct depolarizations=infarct growth
Acute Stroke: Every Minute Counts Estimated Pace of Neural Circuitry Loss in Typical Large Vessel, Supratentorial Acute Ischemic Stroke Neurons Synapses Myelinated Accelerated Lost Lost Fibers Lost Aging Per Stroke 1.2 billion 8.3 trillion 7140 km/4470 miles 36 yrs Per Hour 120 billion 830 billion 714/447 miles 3.6 yrs Per Minute 14 billion 12 km/7.5 miles 3.1 weeks 1.9 million Per Second 32,000 230 million 200 meters/218 yards 8.7 hours 27
IV TPA Improves Recanalization 13:02 Time 13:38 Circulation 2000;100:2282-83 TPA bolus
Time is Brain Pooled Analysis NINDS tPA; ATLANTIS; ECASS-1,2,3; EPITHET ~4h 30min
All tPA trials: Elderly benefit too
TPA Recanalization Rates 1h 2h 24h delZoppo et al 1992 Saqqur et al 2007 Zangerle et al 2007 8% 6% 46% 26% 30% 53% 35% 44% 68%
Combination systemic thrombolysis treatment Recanalization More Frequently, Faster and Completely + + +
The Evolution of Endovascular Treatment IA drip 1990s IA drip & wire Health Canada approvals Merci 2003 2008 Penumbra Stentriever - 2010 TREVO Stentriever - 2012 SOLITAIRE FR 34
90-Day mRS Distribution All Subjects Differences between the two treatment groups across the entire distribution of the mRS (p = 0.25, van Elterin test)
90-Day mRS Distribution, Baseline CTA: Carotid T/L or Tandem ICA+M1 27.3% 4.3%
The Evolution of Endovascular Treatment IA drip 1990s IA drip & wire Health Canada approvals Merci 2003 2008 Penumbra Stentriever - 2010 TREVO Stentriever - 2012 SOLITAIRE FR 40
TICI Reperfusion by Primary Target Occlusion Percent with TICI 2b-3 at completion Primary Target Vessel Frequency of procedure All 328 40% ICA Intracranial 65 38% M1 135 44% Single M2 61 44% Multiple M2 s 22 23% M3 20 25%
Revascularization Predicts Good Outcome For ICA, M1 Occlusion TICI=0 TICI=1 TICI=2a TICI=2b TICI=3 n= 32 n= 16 n= 67 n= 80 n= 5 3.1% 12.5% 19.4% 46.3% 80% % 90 Day mRS 0-2 13.9% 48.2% p < .0001
Safety: ICH – Endovascular Group All Occlusions (Cont’d) Other Standard Ekos Merci Penumbra (Protocol Microcatheter Violations) No No No No No t-PA t-PA t-PA t-PA t-PA t-PA t-PA t-PA t-PA t-PA n= 132 n= 3 n= 22 n= 0 n= 57 n= 37 n= 38 n= 15 n= 8 n= 7 PH-1 or 8.1% 9.1% 14.9% 9.4% 6.7% PH-2 SAH 6.8% 9.1% NA 29.8% 8.1% 7.9% 20.0% 12.5% 28.6% New Emboli 21.1 % 23.7% 0.0% 12.5% 11.1% 42.9% 4.3% 4.5% NA (Core Lab) Perforation 0.0% 5.3% 0.0% 6.3% 0.0% 0.0% 0.0% NA 0.0% (Core Lab) Dissection 0.7% 0.0% NA 1.8% 2.6% 2.6% 12.5% 0.0% 14.3% (Operator) Death 17.9% 18.2% NA 26.3% 34.2% 10.5% 25.0% 33.3% 42.9% 90 days
Descriptive Characteristics Time Parameters Time from Symptom Onset to IA End/Reperfusion Mean (SD) = 325 ( ± 52) min Range 180-418 min Time from Time Time from Onset Groin from Time from IV Start to to IV Start Puncture IA Start Groin Puncture 121 ±34 to IA Start to IA End 81 ±27 min 42 ±21 81 ±43 min min min 0 50 100 150 200 250 300 Minutes
Onset to Balloon Mortality lesson
Time to Reperfusion and Good Clinical Outcome Observed Vs Predicted . ICAT, M1, and M2 Cases with Reperfusion with 95% confidence bands (p=0.0045) Observed values shown as horizontal bars for every ~20 subjects
The Evolution of Endovascular Treatment IA drip 1990s IA drip & wire Health Canada approvals Merci 2003 2008 Penumbra Stentriever - 2010 TREVO Stentriever - 2012 SOLITAIRE FR 48
Thrombectomy devices – “ Stentrievers ” Solitaire TM FR 49
Pre-stentriever Era Trials 14/434 0/70 23/181
Central Core Lab Adjudicated TICI Scores 90 80 70 60 50 40 Series 1 TICI 2b 30 Series 2 TICI 3 20 TICI 2b-3 Series 3 10 0 IMS1&2 MR-RESCUE IMS3 MERCI:Tv2 Swift TREVO:Tv1 Tv2 SolFR: retro Swift STAR
Multiphase CTA Phase� 2� Site� of� Occlusion� Phase� 1� Phase� 3� � � � � � � � � � � � � � � � � � � � � � � � � � Good� Collaterals� Poor� Collaterals�
ESCAPE trial E ndovascular treatment for S mall C ore and A nterior circulation P roximal occlusion with E mphasis on minimizing CT to recanalization times
Future Reality Time from Symptom Onset to IA End/Reperfusion Mean (SD) = 150 ( ± 60) min Range 100-600 min Time from Time Groin from Time from Onset Time from IV Start to Puncture IA Start to IV Start Groin Puncture to IA Start to IA End 121 ±34 81 ±27 min 42 ±21 81 ±43 min min min 0 50 100 150 200 250 300 Minutes
Time to Reperfusion and Good Clinical Outcome Observed Vs Predicted . ICAT, M1, and M2 Cases with Reperfusion with 95% confidence bands (p=0.0045) Observed values shown as horizontal bars for every ~20 subjects
Thank-you for your attention!
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