Mechanical thrombectomy and the future of stroke
Dr Ken FaulderInterventional NeuroradiologistWestmead and Royal North Shore Hospitals
N/A
Inci
denc
e R
ate
(%)
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
N/A
Inci
denc
e R
ate
(%)
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