Update on the acute treatment of stroke patient selection and - - PowerPoint PPT Presentation

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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

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

Coull et al. BMJ 2004

Minor Cerebrovascular Syndrome

Most Neuro Spells are TNAs Transient Neurologic Attacks Non-ischemic ischemic

TIA Risk Stratification: Clinical

Benign/low risk Intermediate risk Malignant/high risk

Timing since event

months weeks days hours minutes

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

Left MCA Probe RACA Ultrasound Beam Axis LACA

CT-angio arch/vertex perfect for highr risk TIA

Basilar stenosis

Carotid stenosis Carotid ILT Aortic dissection Aortic thrombus

iNOT

Protruding aortic plaque MCA occlusion Basilar stenosis Terminal ICA stenosis

34 ml 8 ml 140 ml 41 ml 68 ml

34 ml 8 ml 140 ml 41 ml 68 ml

Proportion independent

• utcome

mortality

Intracerebral Hemorrhage

8 ml 68 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

2.5 hours after symptom onset

6.5 hours after onset, with enlargement of the hematoma due to ongoing bleeding

“Early Hematoma Growth” One in Three DRIP in front of our eyes

34 ml 8 ml 41 ml

time

n=2800 enrollment complete Results May 2013

CTA Spot Sign + rFVIIa trials

Ischemic Stroke

Peri-infarct depolarizations=infarct growth

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Estimated Pace of Neural Circuitry Loss in Typical Large Vessel, Supratentorial Acute Ischemic Stroke

Neurons Lost Synapses Lost Myelinated Fibers Lost Accelerated 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

1.9 million

14 billion 12 km/7.5 miles 3.1 weeks Per Second 32,000 230 million 200 meters/218 yards 8.7 hours

Acute Stroke: Every Minute Counts

13:02 Time 13:38 TPA bolus

IV TPA Improves Recanalization

Circulation 2000;100:2282-83

Time is Brain

~4h 30min

Pooled Analysis NINDS tPA; ATLANTIS; ECASS-1,2,3; EPITHET

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

+ + +

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The Evolution of Endovascular Treatment

IA drip IA drip & wire Merci Penumbra Stentriever - TREVO Stentriever - SOLITAIRE FR

1990s 2003 2008 2010 2012

Health Canada approvals

Differences between the two treatment groups across the entire distribution of the mRS (p = 0.25, van Elterin test)

90-Day mRS Distribution All Subjects

90-Day mRS Distribution, Baseline CTA: Carotid T/L or Tandem ICA+M1

27.3% 4.3%

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The Evolution of Endovascular Treatment

IA drip IA drip & wire Merci Penumbra Stentriever - TREVO Stentriever - SOLITAIRE FR

1990s 2003 2008 2010 2012

Health Canada approvals

TICI Reperfusion by Primary Target Occlusion

Primary Target Vessel Frequency Percent with TICI 2b-3 at completion

• f 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 % 90 Day mRS 0-2 3.1% 12.5% 19.4% 46.3% 80% 13.9% 48.2% p < .0001

Safety: ICH – Endovascular Group All Occlusions (Cont’d)

Standard Microcatheter Ekos Merci Penumbra Other (Protocol Violations) t-PA No t-PA t-PA No t-PA t-PA No t-PA t-PA No t-PA t-PA No 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 PH-2

8.1% 9.1% 14.9% 9.4% 6.7%

SAH 6.8% 9.1% NA 29.8% 8.1% 7.9% 20.0% 12.5% 28.6%

New Emboli (Core Lab)

4.3% 4.5% NA

21.1% 23.7% 0.0% 12.5% 11.1% 42.9%

Perforation (Core Lab)

0.0% 0.0% NA 0.0% 5.3% 0.0% 6.3% 0.0% 0.0%

Dissection (Operator)

0.7% 0.0% NA 1.8% 2.6% 2.6% 12.5% 0.0% 14.3%

Death 90 days

17.9% 18.2% NA

26.3% 34.2% 10.5% 25.0% 33.3% 42.9%

Descriptive Characteristics

Time Parameters

Time from Onset to IV Start 121 ±34 min

Time from IV Start to Groin Puncture 81 ±27 min Time from Groin Puncture to IA Start 42 ±21 min Time from IA Start to IA End 81 ±43 min 50 100 150 200 250 300 Minutes

Time from Symptom Onset to IA End/Reperfusion Mean (SD) = 325 (±52) min Range 180-418 min

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

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The Evolution of Endovascular Treatment

IA drip IA drip & wire Merci Penumbra Stentriever - TREVO Stentriever - SOLITAIRE FR

1990s 2003 2008 2010 2012

Health Canada approvals

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Thrombectomy devices – “Stentrievers”

SolitaireTM FR

Pre-stentriever Era Trials

14/434 0/70 23/181

10 20 30 40 50 60 70 80 90 Series 1 Series 2 Series 3

TICI 2b TICI 3 TICI 2b-3

IMS1&2 MR-RESCUE IMS3 MERCI:Tv2 Swift TREVO:Tv1 Tv2 SolFR: retro Swift STAR

Central Core Lab Adjudicated TICI Scores

Site

• f

Occlusion

• Phase

1

• Phase

2

• Phase

3 Good Collaterals Poor Collaterals

Multiphase CTA

ESCAPE trial

Endovascular treatment for Small Core and Anterior circulation Proximal

• cclusion with Emphasis on minimizing CT to recanalization times

Future Reality

Time from Onset to IV Start 121 ±34 min

Time from IV Start to Groin Puncture 81 ±27 min Time from Groin Puncture to IA Start 42 ±21 min Time from IA Start to IA End 81 ±43 min 50 100 150 200 250 300 Minutes

Time from Symptom Onset to IA End/Reperfusion Mean (SD) = 150 (±60) min Range 100-600 min

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!