Mechanical thrombectomy and the future of stroke

Dr Ken FaulderInterventional NeuroradiologistWestmead and Royal North Shore Hospitals

N/A

Inci

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ate

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IV-rtPAPlacebo

NINDS* (National Institute of Neurological Disorders and Stroke rt-PA Stroke Study Group)

*AJNR 30:859-75: May 2009

NINDS demonstrated that IV-tPA is

safe and more effective than Placebo in the

0-3 hour window.

28.0%

24.0%

1.0%

39.0%

21.0%

7.0%

0%

5%

10%

15%

20%

25%

30%

35%

40%

45%

Recanalization Good Outcome (mRS 0-1) Mortality Symptomatic ICH

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IV-rtPAPlacebo

ECASS III (European Cooperative Acute Stroke Study)

N Engl J Med. 2008 Sep 25;359(13):1317-29 .

ECASS III extended the window of care for IV tPA treatment to 4.5 hours.

49.2%

8.4%

0.2%

52.4%

7.7%

2.4%

0%

10%

20%

30%

40%

50%

60%

Recanalization Good Outcome Mortality Symptomatic ICH

IV tPA – Recanalization at One Hour (angiographic data)

Del Zoppo et al., Ann Neurol 1993

• IV-rtPA recanalization rates for large vessel occlusions in comparison to smaller vessel occlusions is lower.

31%

8%

24%

35%

40%

0%

5%

10%

15%

20%

25%

30%

35%

40%

45%

All ICA MCA Stem MCA Divsn MCA Branch

% Recanalized

Effect of site of occlusion on clinical outcome

Published June 21, 2012 as 10.3174/ajnr.A3149

Strokes treated in NINDS trial in fact a heterogenous group

Perforator, M3, M2, M1, ICA

TPA does not work in long M1 or ICA occlusions, TPA wrong treatment and prevents or delays correct triage to IA treatment

REVASCULARIZATION AND GOOD OUTCOME

Rha Meta-analysis

Recanalized: 58% good outcome

Non-recanalized: 25% good outcome

53 studies, 2066 patientsMorbidity and mortality at 3 monthsStrong association with recanalisation & good outcomeRecanalisation is appropriate biomarker of therapeutic activityStroke 2007

Variability and reversibility of focal cerebral ischaemia in unanesthetized monkeys

Cromwell RM et alStroke lab, Uni of MassachusettsNeurology October 198131(10):1295-1302

‘neurologic improvement was common after the release of occlusion. …frequent with 30-min and 4-hour occlusions

…was observed even after 16 hours’

Time is Brain - Quantified

1.9 Million Neurons lost every minute

Calculations on growth function of a ‘typical’ large vessel ischaemic stroke

Used ‘linear growth function’ to calculate neuronal loss over time

Personal observation is that if there is recanalization, final infarct refects core volume at time of perfusion, raises question whether infarct growth linear

J Saver - Stroke 2005

70 yo man, acute left hemispheric stroke, presents at 2 hours

Is this patient better off if given TPA?

Poor outcome in patients defined as malignant perfusion had poor outcome (100%) vs non malignant scans (7.1%)

Stroke 2012;43:0-0

72 yo woman dense left hemiplegia 4 hrs post onset, NIHSS 12

The independent predictive utility of computed tomography angiographic collateral status in acute ischaemic stroke

Miteff F et alBrain 2009:132:2231-2238

Evolution of technique

Early days of IA lysis, patients treated with intra-arterial rTPA or Urokinase

ProAct II, clinical outcomes promising but concern over incidence of symptomatic intracerebral haemorrhage ~10%

Early mechanical devices initially promising but difficult to use, long procedures and 70-80% recannalization

Evolution of technique

IMS III◦ Trial comparing IV thrombolysis and

combined IV thrombolysis and intraarterial clot retrieval

◦ Early 2012, study stopped early because of futility

◦ Several criticisms of study design, most importantly 1st generation devices, Merci, Ekos

◦ Secondly, time delay to institution of IA therapy

AJNR Am J Neuroradiol. 2011 Jun-Jul;32(6):1078-81. doi: 10.3174/ajnr.A2447. Epub 2011 Apr 14.Mechanical thrombectomy with a self-expanding retrievable intracranial stent (Solitaire AB): experience in 26 patients with acute cerebral artery occlusion.Miteff F, Faulder KC, Goh AC, Steinfort BS, Sue C, Harrington TJ.

26 consecutive stroke patients treated with solitaire embolectomy device94% recannalization56% good clinical outcome mRS 0-2 at 90 days

20% good outcome in basilar occlusions

Solitaire fow restoration device versus the Merci Retriever in patients with acute ischaemic stroke (SWIFT): a randomised, parallel-group, non-inferiority trial – Lancet August 2012

Study designed to show equivalence of newer solitaire device with Merci retriever

55 pts treated with Merci device, 58 with Solitaire

Good clinical outcome at 90 days

Merci 33%, Solitaire 58%

Newer Mechanical Devices

Newer Mechanical Devices STAR trial (incl RNSH)◦ Single arm international multicentre study

◦ Failed IV or IV ineligible, large vessel occlusion

◦ Revascularization 94.7%

◦ ICH 1.5%

◦ Mortality 6.9%

◦ mRS 0-2 at 90 days 57.9%

Ninds

ICH 7%, Mortality 21%, Good outcome 39%

Intra-arterial Treatment Future Clearly place for IV and IA treatment

Effectiveness dependent on site of occlusion and time to treatment

Future trial design aimed at ◦ better patient selection, CTA and perfusion

◦ IV ineligible or predicted low success rate

◦ IV ineligible patients

Success in stroke treatment will depend upon correct treatment pathways and protocols for urgent intervention