Jianliang Lin, Sterling Meyers, Brajendra Mishra, Sudipta Bhattacharyya,
Interventional Stroke Treatment 2015 Sudipta Roychowdhury, MD Director of Interventional...
-
Upload
verity-turner -
Category
Documents
-
view
224 -
download
0
Transcript of Interventional Stroke Treatment 2015 Sudipta Roychowdhury, MD Director of Interventional...
Interventional Stroke Treatment 2015
Sudipta Roychowdhury, MD
Director of Interventional NeuroradiologyDirector of Magnetic Resonance ImagingClinical Associate Professor of Radiology
Rutgers-RWJ Medical SchoolUniversity Radiology Group
Stroke Therapy Timeline
19951995 20002000 20052005 20102010
IV tPA IV tPA MERCIMERCIPROACT IIPROACT II
IA tPAIA tPA
PenumbraPenumbra
ACEACE
SolitaireSolitaire
IV tPA (4.5h)IV tPA (4.5h)
AngioplastyAngioplastyStentingStenting
Generation 1Generation 1 Generation 3Generation 3Generation 2Generation 2
Off-label - RedOff-label - RedFDA Approved - Yellow FDA Approved - Yellow
Bridging IV/IABridging IV/IA TrevoTrevo
20152015
Level I Level I EvidenceEvidence
MR CLEANMR CLEANSWIFT PRIMESWIFT PRIME
EXTEND IAEXTEND IAESCAPEESCAPE
REVASCATREVASCATTHERAPYTHERAPY
Ischemic Stroke Therapy FDA Small Series Large Trial Efficacy
IV t-PA Yes Yes Yes
IA t-PA No Yes No
IV and IA t-PA No Yes No
MERCI Device Yes Yes No
Penumbra Device Yes Yes Yes
Solitaire Device Yes Yes Yes
Trevo Device Yes Yes Yes
Angioplasty/Stenting No Yes No
Ischemic Stroke Interventions
NINDS tPA Trial• NINDS tPA trial (1995)
– IV tPA vs Placebo < 3hrs– Outcomes improved with all 4 outcomes
Symptomatic hemorrhage 6.4% vs 0.6%– Mortality 17% vs 21% placebo at 3 months– Established IV tPA as gold standard < 3hrs– Better for small rather than large occlusions
• Benefit still seen 3-4.5 hours NEJM 9/2008 European study
PROACT II
• PROACT II (1998) – Dr. Irwin Keller NJ Investigator
– IA Prourokinase < 6 hrs– Favorable outcome 40% vs 25% control– Recanalization 66% vs 13% control– Mortality 25% vs 27% control– Symptomatic hemorrhage 10% vs 2% control– IA Prourokinase and tPA not FDA approved
Case
• 55 y/o M presents after 5 hours of onset of rapidly progressive quadriparesis, ataxia, and dysphagia.
• Head CT was normal.
Basilar Artery Occlusion Basilar Artery Occlusion
Basilar Angioplasty and Thrombolysis IA t-PA
Excellent Recanalization and Excellent Outcome
Case
• 77 y/o F presents after 4 hours of onset of slurred speech and ataxia rapidly progressing to loss of consciousness
• Head CT was unremarkable.
Basilar Artery Occlusion
Basilar Angioplasty/Stent & Thrombolysis IA t-PA
Futile Recanalization
MERCI Device
MERCIMERCI
MERCI Trial• MERCI (2005)
– MERCI < 8 hrs; n=141; No control arm– Recanalization 46% (66% PROACT II)– Mortality 44% (25% PROACT II, 27% Control)– Symptomatic hemorrhage 7.8%– Primary outcome recanalization not outcome– Results worse than PROACT II– FDA approved but heavily criticized for
approval before establishing efficacy
Multi-MERCI Trial
• Multi- MERCI (2006) – MERCI +/- IV tPA < 8 hrs; n=164; No control– Recanalization 54% and 69% w IA tPA– Mortality 31%; Symptomatic hemorrhage 9%– Primary outcome recanalization not outcome– Results still worse than PROACT II– Still trying to establish efficacy after FDA
approval!
Does the MERCI Device Work?• “In summary, the MERCI study does not provide
any evidence of improved outcomes or greater recanalization rates…. In addition, both clinically significant complications and mortality are higher than the results of other interventional trials…. the results do not support the proposal that the Merci retrieval device works by any definition.”
Wechsler, Lawrence R. MD, Donnan, Geoffrey A. Wechsler, Lawrence R. MD, Donnan, Geoffrey A. MD, FRACP; Davis, Stephen M. MD, FRACPMD, FRACP; Davis, Stephen M. MD, FRACPStroke Volume 37(5), May 2006, pp 1341-1342 Stroke Volume 37(5), May 2006, pp 1341-1342
MERCI: Defended
• Why high recanalization but not better outcomes?
• Comparing MERCI to PROACT II• Different pt selection – MERCI trials included pts
with poor functional status unlike PROACT II• If adjust for patient selection, similar mortality
and outcome
Case
• 38 y/o F presents with acute left sided hemiplegia presents at 4 hours. History of atrial fibrillation.
• Head CT was unremarkable.
MERCI
Penumbra Device
Suction catheter with separator wire which Suction catheter with separator wire which prevents thrombus from clogging the tipprevents thrombus from clogging the tip
Penumbra Trial
• Penumbra – n=125; Recanalization 82% (PROACT II 66%) – Mortality 32% (25% PROACT II, 27% Control)– Symptomatic hemorrhage 11%– Primary outcome recanalization – 36% good outcome; No control arm– 510k FDA approval – “equivalent” to MERCI
Case
• 44 y/o M presents with mental status changes and left leg weakness at 6 hours.
• Head CT was unremarkable.
Penumbra ACA Infarct
Stent Retrievers
• 3rd Generation endovascular stroke treatment• Immediate flow restoration• Trap thrombus within stent struts and retrieved• Removable device so no anti-platelets needed
TrevoTrevo
SolitaireSolitaire
Solitaire
Solitaire – SWIFT Trial
• SWIFT (SOLITAIRE With the Intention for Thrombectomy) • Solitaire (S) versus Merci (M) randomized trial 200 intended pts but
stopped at 144 by safety board• Successful recanalization without symptomatic hemorrhage –
occurred in 61% of the Solitaire group and 24% of the Merci group. Highly significant difference with a P value of .0001
• Symptomatic intracranial hemorrhage (2% S vs. 11% M). • All intracranial hemorrhage (17% S vs. 38% M). • Good 90-day neurologic outcome (58% S vs. 33% M). • 90-day mortality (17% S vs. 38% M).
• Solitaire was significantly better than Merci
Case
• 65 y/o M presents acute left sided hemiplegia at 4 hours and was on Coumadin for atrial fibrillation.
• Head CT was unremarkable.
Solitaire
Trevo
• Trevo 2 Trial : Trevo versus Merci retrievers for large vessel stroke
• Randomized Trevo Retriever group 88 patients and Merci Retriever group 90 pts
• 76 (86%) patients in the Trevo group and 54 (60%) in the Merci group met the primary endpoint after the assigned device. p<0·0001).
• Incidence of the primary safety endpoint did not differ between groups (13 [15%] patients in the Trevo group vs 21 [23%] in the Merci group; p=0·1826).
• Trevo was significantly better than Merci
Futile RecanalizationUnfavorable outcome even with excellent
endovascular recanalization
How do we select Stroke Patients to avoid Futile Recanalization?
• Time versus Penumbra versus Core • Time
– Less than 6 hours for IA tPA (Anterior)– Less than 8 hours for mechanical (Anterior)– Unknown time for posterior circulation
• Penumbra – Potential stroke territory– CT perfusion – very controversial
– Not accurate predictor of penumbra– High radiation dose– Fallen out of favor by MGH original CTP advocates
– Delayed CTA images for collaterals
How do we select Interventional Ischemic Stroke Patients?
• Core – Actual irreversibly infarcted brain tissue– If less than 1/3 of MCA territory has been infarcted,
better chance for good outcome with recanalization– If the Core is smaller with larger penumbra, the
patient may have good collaterals which will allow better outcome with recanalization.
• ASPECTS criteria• MRI diffusion
ASPECTS Criteria
• Alberta Stroke Program Early CT score (ASPECTS) is a 10-point CT scan score
• ASPECTS predicts core of infarct• A normal CT scan receives ASPECTS of 10 points. • To compute the ASPECTS, 1 point is subtracted from 10
for any evidence of early ischemic change for each of the defined regions OF MCA territory
• A score of 0 indicates diffuse involvement throughout the MCA territory
• Patients with ASPECTS score of 8-10 had better outcomes than patients with 7 or less at both shorter (less 5 hours ) and longer (greater than 5 hours) recanalization
ASPECTS Criteria
• A normal CT scan receives ASPECTS of 10 points. • To compute the ASPECTS, 1 point is subtracted from 10
for any evidence of early ischemic change for each of the defined regions OF MCA territory
MR Diffusion Criteria
• MR diffusion accurately predicts core of infarct• If less than 1/3 MCA territory or less than 70ml volume,
better outcome endovascular treatment (Volume = ABC/2)• If brainstem infarcted in posterior circulation, poor outcome
with basilar stroke.• Takes additional time to obtain MR diffusion
Diffusion (Core)Diffusion (Core) PWI (Penumbra)PWI (Penumbra)
TICI Criteria for M1 Occlusion
• Grade 0 – No antegrade flow beyond occlusion
• Grade 1 – Open beyond obstruction but not
distal• Grade 2a – Less 50% MCA
circulation• Grade 2b – Greater than
50% MCA circulation• Grade 3 – Entire MCA
circulation open
• Grade 2B and 3 – Best neurological outcomes
Case 6
• 76 y/o F noted to have left arm/leg weakness 2 days after pelvic surgery.
Core: MR Diffusion
MR Diffusion: less than 1/3 MCA core infarctMR Diffusion: less than 1/3 MCA core infarct
MR DiffusionMR DiffusionHead CTHead CT CTA – R M1 occlusionCTA – R M1 occlusion
CT Perfusion and MR Diffusion
Diffusion (Core)Diffusion (Core)TTP (Penumbra)TTP (Penumbra)CBF CBF
Penumbra Device
CT Perfusion after Penumbra Thrombectomy
DiffusionDiffusionTTP after TTP after thrombectomythrombectomy
TTPTTP
IMS III (2008-2012)
• Interventional Management of Stroke III
• NEJM March 2013 results – IV tPA only vs IV + IA tPA / Mechanical
– Trial stopped in 2012 as ongoing data could not show benefit of combined IV+ IA superior to IV tPA alone
– No distinction between small and large vessel strokes– Large vessel occlusions did better with IA– Limited by older endovascular devices– No CTA, No ASPECTS criteria
SYNTHESIS Expansion Trials
• NEJM March 2013– IV tPA only <3 hrs vs Combined IV + IA tPA and/or
Mechanical Device < 6hrs– Can we do better than IV tPA?– Endocvascular Tx: Catheter & wire, Merci and
Penumbra, minimal Stent-Retrievers– Limited by older endovascular devices– No difference in outcomes– No distinction between large and small vessel strokes
Level I Interventional Evidence
• MR CLEAN• ESCAPE
• EXTEND-IA• SWIFT PRIME• REVASCAT• (THERAPY)
MR CLEAN Study Details
• Control – IV/Medical only versus Interventional arm - IA and IV• MR CLEAN demonstrated a 71% improvement in good neurological
outcomes for Interventional compared to medical management/TPA (32.6% (76/233) vs. 19.1% (51/267))
• There was no safety difference in adverse events (47% vs. 42%) , ICH (7.8% vs. 6.4%) or 90 day mortality (21% vs 22%) between the two groups.
• Lower absolute rates of 90day mRS 0-2 and higher complication rates seen in MR CLEAN vs. prior studies reflect the ‘real-world’ experience in the Netherlands, particularly the relatively high rate of ICA lesions vs. prior studies like IMS3 (26% vs. 15%)
• Stent Retrievers used in 97% of interventions• There was a improved mRS shift for Interventional vs Control• First large scale study demonstrating interventional superiority
||
MR CLEAN mRS
mRS (Modified Rankin Scale)mRS (Modified Rankin Scale)
0 – No symptoms0 – No symptoms1 – No significant disability1 – No significant disability2 – Slight disability2 – Slight disability3 – Moderate disability3 – Moderate disability4 – Moderate severe disability4 – Moderate severe disability5 – Severe disability5 – Severe disability6 – Death6 – Death
• In patients with acute ischemic stroke caused by a large
arterial occlusion of the anterior circulation, intraarterial
treatment within 6 hours was effective and safe
• IA treatment leads to a clinically significant increase in the
functional independence in daily life by 3 months, without an
increase in mortality
• Triggered stoppage of multiple other trials: ESCAPE, SWIFT
PRIME, Extend IA, REVASCAT, and THERAPY
MR CLEAN Study Conclusion
O.A. Berkhemer et. al. A Randomized Trial for Intraarterial Treatment for Acute Ischemic O.A. Berkhemer et. al. A Randomized Trial for Intraarterial Treatment for Acute Ischemic Stroke. N Eng J Med December 2014.Stroke. N Eng J Med December 2014.
Trial
Imaging Required to Confirm Occlusion
Prior to Randomization?
Device(s) Used in Intervention Arm
TICI 2b/3 Revascularization
Rate in the Intervention Arm
mRS 0-2
Intervention Arm Control Arm
IMS III No
IA Lytic (138), Merci Retriever® (95), EKOS (22), Penumbra (54), Solitaire FR (5)
38% ICA44% M144% M2
23% multi M2
40.8%(N=415)
38.7%(N=214)
MR RESCUE No Merci Retriever®, EKOS, IA Lytic, Penumbra
24% pen(n=34)
27% nonp(n=30)
21% pen (n=34)
17% nonp(n=30)
26% pen (n=34)
10% nonp(n=20)
MR CLEAN Head CT 97% Stent Retrievers, 2% other Mechanical
58.7% (N=196)
33% (N=233)
19% (N=267)
ESCAPE CTA Collaterals, ASPECTS 86% Stent Retriever 72.4%
(n=156)53.0%
(n=164)29.3%
(n=147)
SWIFT PRIME CTP 100% Stent Retriever 88.0%(n=83)
60.2%(n=98)
35.5%(n=93)
EXTEND-IA CTP 100% Stent Retriever 86.2%(n=29)
71%(n=35)
40%(n=35)
REVASCAT ASPECTS 100% Stent Retriever 66%(n=102)
44%(n=102)
28%(n=103)
THERAPY CTA clot >8mm 100% Penumbra 38%(n=50)
30%(n=46)
• Interventional therapy (with IV tPA) may have become the
gold standard for large vessel ischemic stroke in 2015.
– MR CLEAN, ESCAPE, SWIFT PRIME, REVASCAT, EXTEND-IA, THERAPY
• However, the selection criteria for interventional stroke
treatment is not uniform.
– Head CT, ASPECTS, Diffusion MRI, CTA, Delayed CTA, CTP
• Medicolegal Implications: Large vessel ischemic stroke
patients may need to have rapid access to Interventional tx.
What does this mean?
Case
• 38 F who is 16 weeks pregnant presented with slurred speech and facial weakness to the ER after 8 hours. She became comatose after 24 hours after admission. MRI performed at 30 hours. Angiogram performed at 36 hours after emergency hospital privileges.
38 y/o Comatose F
Angiogram at 36 hrsAngiogram at 36 hrs
Basilar Artery Angioplasty and Thrombolysis at 36 Hours
Ischemic Stroke Treatment Guidelines
• IV tPA (<4.5 hours) • Add Interventional (IA) treatment if:
– Do CTA if MCA syndrome or NIHSS > 7– CTA shows large vessel occlusion– Patient not a IV t-PA candidate – Patient not improving with IV t-PA– ASPECTS criteria 8-10 for MCA stroke– MR diffusion shows small or no core infarct
• Transfer to comprehensive stroke center if large vessel stroke
• Need to await further results of trials• “Do no harm…”
Interventional Stroke Treatment 2015
Sudipta Roychowdhury, MD
Director of Interventional NeuroradiologyDirector of Magnetic Resonance ImagingClinical Associate Professor of Radiology
Rutgers-RWJ Medical SchoolUniversity Radiology Group
Stroke Therapy Timeline
19951995 20002000 20052005 20102010
IV tPA IV tPA MERCIMERCIPROACT IIPROACT II
IA tPAIA tPA
PenumbraPenumbra
ACEACE
SolitaireSolitaire
IV tPA (4.5h)IV tPA (4.5h)
AngioplastyAngioplastyStentingStenting
Generation 1Generation 1 Generation 3Generation 3Generation 2Generation 2
Off-label - RedOff-label - RedFDA Approved - Yellow FDA Approved - Yellow
Bridging IV/IABridging IV/IA TrevoTrevo
20152015
Level I Level I EvidenceEvidence
MR CLEANMR CLEANSWIFT PRIMESWIFT PRIME
EXTEND IAEXTEND IAESCAPEESCAPE
REVASCATREVASCATTHERAPYTHERAPY