current endovascular management of ischemic stroke cuellar/endovascular management of... · current...

Current endovascular management of ischemic stroke

Hugo Cuellar, MD, PhDAssociate Professor of Neurosurgery

and RadiologyDirector of Neuronterventional Surgery

Disclosures

• Nothing to disclose

Objectives

• Evaluate latest technology for intracranial thrombectomy.

• Analize the results of latest endovascular trials for acute ischemic stroke.

Ischemic stroke

• Ischemic stroke usually results when an artery to the brain is blocked by a thrombotic or embolic occlusion and is more common than hemorrhagic stroke.

• If the clot breaks up spontaneously within less than 15 to 30 minutes, brain cells do not die and people's symptoms resolve. Such cases are called a transient ischemic attack (TIA).

• 20% mortality – 40% moderate to severe deficits.

Ischemic stroke

• Stroke is the leading cause of disability and the fourth leading cause of death in the United States.

• 82-92% of strokes in the United States are ischemic.

• Approximately 795,000 people in the United States experience new (610,000 people) or recurrent (185,000 people) stroke.

Roger VL, Go AS, Lloyd-Jones DM, Benjamin EJ, Berry JD, Borden WB, et al. Heart disease and stroke statistics--2012 update: a report from the American Heart Association. Circulation. Jan 3 2012;125(1):e2-e220

Ischemic stroke

• Major risk factors: Atherosclerosis, High cholesterol, HTA, Diabetes, Smoking

• Consider stroke in any patient presenting with acute neurologic deficit or any alteration in level of consciousness.

• Initial goals: Confirm presence of stroke (CT-CTA), establish a baseline, establish severity (NIHSS), determine time of onset if possible.

Treatment

• IV- tPA

• 1996 FDA approved 0-3 hrs

• 2006 extend to 4.5 hrs

• AHA advisory.

• FDA had no position since 2008

• IV tPA 3-4.5hrs FDA approved with additional exclusions.

• In NINDS trial only 8% had favorable outcome if NIHSS> 20.

IV thrombolysis

• Rapid administration

• Greatest benefit in 60-90 minute window

• Efficacy decreases with time

• Efficacy decreases with burden of thrombus.

• 33% distal MCA

• 15% proximal MCA

• 24% tandem ICA/MCA

• 25% basilar artery

• 0% ICA ‘T’ occlusion

Stroke 2007. 38:948-952

Treatment

• Neurointerventional stroke rescue has grown rapidly over the last years.

• In addition to the oldest techniques that use IA tPA, we have a new expanding field of mechanical devices for fast revascularization.

• Time remains the most important part of stroke rescue.

Mazighi M, et al. Comparison of intravenous alteplase with a combined intravenous-endovascular approach in patients with stroke and confirmed arterial occlusion. Stroke 2009.

Evolution

• Intraarterial tPA -1998

• Mechanical embolus removal in cerebral ischemia (MERCI) FDA 2004.

• CATCH device 2005-EU

• PENUMBRA aspiration-2009 FDA

• SOLITAIRE-TREVO stent retrievers- 2012 FDA

MRCLEAN Study overview

Source: http://www.mrclean-trial.org/index.html, accessed 05Jun2014

Study MR CLEAN

Enrollment Period December 2010 – March 2014

Study Design Prospective, multi-center, randomized, controlled, blinded-endpoint trial

Tx Window 6 hrs

NIHSS 2 or more

Study ArmEndovascular treatment: intra-arterial thrombolysis (urokinase or alteplase), mechanical treatment (retraction or aspiration of the thrombus with a catheter guided device, or stenting) or both

Control Arm Medical management

Target Vessels Distal ICA, middle (M1/M2) or anterior (A1/A2) cerebral artery

Sample Size/Sites 500 pts, 18 sites in Netherlands

Primary EndpointsmRS at 90 daysRankin Shift

Secondary Endpoints NIHSS at 24 hours, vessel patency at 24 hours, infarct size at day 5-7, and the occurrence of major bleeding

Follow-up 24 hrs, 5-7 days, discharge, 90 days

Key In/ExclusionCriteria

• Intracranial occlusion of the distal intracranial ICA, middle (M1/M2) or anterior (A1/A2) cerebral artery, demonstrated with CTA, MRA, DSA or transcranial Doppler/duplex (TCD).

http://www.mrclean-trial.org/index.html

MR CLEAN Data Overview Baseline Demographics** No significant difference between populations

Characteristic Intervention(N=233)

Control(N=267)

Age in years --‐ median (IQR)65.8 (54.5 to 76.0) 65.7 (55.5 to 76.4)

Male sex – n (%)135 (57.9%) 157 (58.8%)

NIHSS score --‐ median (IQR; range)^17 (14 to 21; 3 to 30) 18 (14 to 22; 4 to 38)

Clinical localization: Left hemisphere – n (%)116 (49.8%) 153 (57.3%)

History of ischemic stroke – N (%) 29 (12.5%) 25 (9.4%)

Atrial fibrillation – n (%)66 (28.3%) 69 (25.8%)

Diabetes mellitus – n (%) 34 (14.6%) 34 (12.7%)

Pre--‐stroke modified Rankin Scale score – n (%)012

>2

190 (81.5%)21 (9.0%)12 (5.2%)10 (4.3%)

214 (80.1%)29 (10.9%)13 (4.9%)11 (4.1%)

N Engl J Med. 2015 Jan 1;372(1):11-20. doi: 10.1056/NEJMoa1411587. Epub 2014 Dec 17.A randomized trial of intraarterial treatment for acute ischemic stroke

Dichotomized mRS

Outcome Difference (95% CI)

mRS 0-1 2.1 (1.1 to 4.0)

mRS 0-2 2.2(1.4 to 3.4)

mRS 0-3 2.0(1.4 to 3.0)

mRS 0-4 1.5(1.0 to 2.4)

mRS 0-5 1.1(0.7 to 1.7)

6.0%

19.1%

35.6%

57.6%

79.0%

11.6%

32.6%

51.1%

63.1%

78.0%

0.0%

10.0%

20.0%

30.0%

40.0%

50.0%

60.0%

70.0%

80.0%

90.0%

mRS 0-1 mRS 0-2 mRS 0-3 mRS 0-4 mRS 0-5Control Intervention


Almost exclusively stent thrombectomy used

190 (97%)

1 (0%)5 (3%) Devices Used

Stent Retrievers

Thrombolysis

Other MechanicalDevices

N= 196 patients


MR CLEAN Rankin Shift Analysis**

0%

3%

6%

9%

13%

21%

16%

18%

30%

22%

12%

6%

22%

21%

0% 20% 40% 60% 80% 100%

Control (N=267)

Intervention (N=233) 0

1

2

3

4

5

6

7


MR CLEAN (EU) SWIFT PRIME (Global) EXTEND IA (AUS, NZ) REVASCAT (Spain) ESCAPE (Global) Therapy (Global)

Randomization of patients to IV TPA vs. IV TPA + Endovascular

Time Window Studied Onset to 6 hours Onset to 6 hours Onset to 6 hours Onset to 8 hours Onset to 12 hours Onset to 5 hours

Trial FundingSupport

Funded by Dutch Heart

Foundation with small support from industry

Funded by CovidienFunded by Covidien

Investigator InitiatedFunded by Covidien

Investigator InitiatedFunded by Covidien

Investigator InitiatedFunded by Penumbra

Number of Patients 500 196 70 ~195 314 ~105

Analysis of Primary Endpoint

Rankin Shift Rankin ShiftReperfusion at 24 hrs

without sICH <72 hours

Rankin ShiftNIHSS 0-2 or mRS 0-2

at 90 daysmRS 0-2 at 90 days

Trial status Presented Trial haltedEfficacy endpoint

metTrial Stopped

Study stopped.Data with DSMB for

analysis.

Efficacy endpoint metTrial Stopped

DSMB reviewed data.Trial ongoing but not

recruiting.

Data Status

Presented at WSC; Data

published in NEJM

Presentation:Feb 11, ISC

publication pending


publication pendingPresentation &

publication pending


publication pending

No presentation or publication of data

scheduled

Primary Device Studied

Not Available Solitaire™ Device Solitaire™ Device Solitaire™ Device Solitaire™ DevicePenumbra™* Aspiration

System

Data will ONLY support evidence

for

All stent retrievers

Solitaire™ DeviceONLY




Penumbra™* Aspiration System

Leading Investigator

DiederikDippel

(Netherlands)

Jeff Saver(USA)

Stephen Davis(Australia)

Tudor Jovin(USA)

Mayank Goyal(Canada)

Jay Mocco(USA)

SWIFT Prime

Reperfusion TICI 2b/3: 88%

EXTEND IA

• Extending the Time for Thrombolysis in Emergency Neurological Deficits – IntraArterial

• An investigator-initiated, multi-center, prospective, randomized, open-label, blinded-endpoint (PROBE) study in ischemic stroke patients receiving intravenous alteplase within 4.5h of stroke onset

EXTEND IA Summary

100% 71%

9%0%

37%

40%

20%

6%

0%

20%

40%

60%

80%

100%

120%

Reperfusion at 24hours

MRS 0-2 at 90 days Mortality at 90days

SiCH

Solitaire™ Device+ IV-TPA IV-TPA Alone

N = 35 N = 35

EXTEND IA

• CT perfusion imaging evidence of salvageable tissue and ischemic core <70ml.

ESCAPE

• Endovascular Treatment for Small Core and Proximal Occlusion Ischemic Stroke.

• Patients were included up to 12 hours from symptom onset. Computed Tomography (CT) and CT Angiography were used to exclude patients with large infarct core or poor collaterals, and document anterior circulation, proximal intracranial occlusion.

• ESCAPE assessed 316 patients and found that the addition of stent thrombectomy doubled patients’ rate of return to functional independence.

Rankin scale

• Among acute ischemic stroke patients with proximal vessel occlusion, small infarct core and good collaterals, rapid endovascular treatment [particularly with the Solitaire™ stent thrombectomy device as recommended primary technique] resulted in significant clinical benefit and reduced mortality.

REVASCAT

• Randomized trial of revascularization with Soilitaire versus best medical therapy in the treatment of acute stroke due to anterior circulation large vessel occlusion within 8 hrs.

• ASPECTS score more than 7 on CT or >6 MRI

What are stentrievers?

• Mechanical Thrombectomy Device that features, a patented overlapping-stent design, is attached to a pusher wire and cannot be implanted.

• Basically, a stent that cannot be left behind.

• 2012 FDA approved, CE marked since Dec 2007.

• Up to 6 hrs or use with advanced imaging.

• Time is relative, we move towards physiologicselection.

• 75-90% TIMI 2-3 recanalization.

• 55 % mRS less than 2 at 90 days.

• Stroke. 2012 Oct;43(10):2699-705. Epub 2012 Jul 31.

Retrospective Multicenter Study of Solitaire FR for Revascularization in the Treatment of Acute Ischemic Stroke.

• Lancet. 2012 Oct 6;380(9849):1231-40. doi: 10.1016/S0140-6736(12)61299-9. Epub 2012 Aug 26.

Trevo versus Merci retrievers for thrombectomy revascularisation of large vessel occlusions inacute ischaemic stroke (TREVO 2): a randomised trial.

Stentrievers (Solitaire-Trevo)

How do they work?

55 yo male with left side hemiparesis. 5 hrs onset.

Stentriever

Ischemic stroke

• What to do?

Stroke symptoms

CT AND CTAHemorrhage/changes?

Stop

Major branch occlusion?

yesno

no Stop

yes

Neurointerventional suite

If 0-4.5 hrs give IVtPA AND

ICA-M2, VBAASPECTS 6-10

2015 AHA/ASA Focused Update

Guidelines for the Early Management of Patients with Acute Ischemic Stroke

Guideline Classifications

CLASS 1 (STRONG) Benefit >>> Risk

Suggested phrases for writing recommendations

• Is recommended

• Is indicated/useful/effective/beneficial

• Should be performed/administered/other

CLASS (STRENGTH) OF RECOMMENDATION

CLASS 2a (MODERATE) Benefit >> Risk


• Is recommended



CLASS 2b (WEAK) Benefit ≥ Risk


• May/might be reasonable

• May/might be considered• Usefulness/effectiveness is unknown/unclear, uncertain or not well

established

CLASS 3: No Benefit (MODERATE) Benefit = Risk


• Is not recommended• Is not indicated/useful/effective/beneficial• Should not be performed/administered/other

CLASS 3: Harm (STRONG) Benefit < Risk


• Is not recommended• Is not indicated/useful/effective/beneficial• Should not be preformed/administered/other

LEVEL A

• High-quality evidence from more than 1 randomized controlled trial



LEVEL B-R (Randomized)

• Moderate-quality evidence from 1 or more randomized controlled trial

• Meta-analysis of moderate-quality randomized controlled trial

LEVEL B-NR (Nonrandomized)

• Moderate-quality evidence from 1 or more well-designed, well-executed nonrandomized studies, observational studies, or registry studies

• Meta-analyses of such studies

LEVEL C

• Randomized or nonrandomized observational or registry studies with limitations of design or execution

• Meta-analyses of such studies

LEVEL E

• Consensus of expert opinion based on clinical experience with evidence is insufficient, vague, or conflicting

LEVEL (QUALITY) OF EVIDENCE

Focused Update Sections

Endovascular Interventions

Imaging Systems of Stroke Care

Section 1 Section 2 Section 3


Imaging Systems of Stroke Care

Section 1 Section 2 Section 3


1) Patients eligible for IV rtPA should receive IV rtPA even if endovascular treatments are being considered (Class I; Level of Evidence A).

new revised unchanged

Strong

2) Patients should receive endovascular therapy with a stent retriever if they meet all the following criteria:

• pre-stroke modified Rankin score (mRS) 0-1

• acute ischemic stroke receiving IV rtPA within 4.5 hours of onset according to guidelines from professional medical societies,

• causative occlusion of the internal carotid artery or proximal middle cerebral artery (M1),

• age 18 years and over,

• National Institutes of Health Stroke Scale (NIHSS) score of 6 or greater,

• Alberta Stroke Program Early Computed Tomography Score (ASPECTS) of 6 or greater, and

• treatment can be initiated (groin puncture) within 6 hours of symptom onset

(Class I; Level of Evidence A).

Endovascular Interventionsnew revised unchanged

Strong

Endovascular Intervention

3) As with IV rtPA, reduced time from symptom onset to reperfusion with endovascular therapies is highly associated with better clinical outcomes. To ensure benefit, reperfusion to TICI grade 2b/3 should be achieved as early as possible and within 6 hours of stroke onset (Class I; Level of Evidence B-R).


Strong


4) When treatment is initiated beyond 6 hours from symptom onset, the benefits of endovascular therapy are uncertain for patients with acute ischemic stroke who have causative occlusion of the internal carotid artery or proximal middle cerebral artery (M1) (Class IIb; Level of Evidence C). Additional randomized trial data are needed.


Weak


5) In carefully selected patients with anterior circulation occlusion who have contraindications to IV rtPA, endovascular therapy with stent retrievers completed within 6 hours of stroke onset is reasonable (Class IIa; Level of Evidence

C). There are inadequate data available at this time to determine the clinical efficacy of endovascular therapy with stent retrievers for those patients whose contraindications are time-based or non-time based (such as prior stroke, serious head trauma, hemorrhagic coagulopathy or receiving anticoagulant medications).


Moderate

Summary

• Mechanical thrombectomy with stentrievers has finally proven better outcomes than IV-tPA alone and has achieved level 1A evidence.

• Use of MRI was discouraged in all studies.

• If faced with a stroke patient:– Order CT and CTA at same time.

– Give IV tpa if indicated and transfer to center with endovascular capabilities.

– Look for major branch occlusion and calculate ASPECTS score

– Rule of 6: NIHSS>6, < 6hrs onset, ASPECTS >6

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