1

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

RACAUltrasound

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 outcome

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

27

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

+ + +

34

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%

40

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

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

% 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

0 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

48

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

49

Thrombectomy devices – “Stentrievers”

SolitaireTM FR

Pre-stentriever Era Trials

14/434 0/70 23/181

0

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

SiteofOcclusion Phase1 Phase2 Phase3GoodCollaterals

PoorCollaterals

Multiphase CTA

ESCAPE trial Endovascular treatment for Small Core and Anterior circulation Proximal

occlusion 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

0 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!