Upload
vuque
View
234
Download
5
Embed Size (px)
Citation preview
Raul G Nogueira, MD
Associate Professor in Neurology,Neurosurgery, and Radiology
Emory University
Director, Neuroendovascular ServiceDirector, Neurocritical Care Service
Grady Memorial HospitalAtlanta, GA
What Do SWIFT and TREVO 2 Tell Us About Stent-Retrievers?
Disclosures:
Stryker Neurovacular/ Concentric Medical
Trevo-2 Trial PI, DAWN Trial PI
Physician Advisory Committee
Covidien/ ev3 Neurovacular
SWIFT and SWIFT-PRIME Steering Committee
Physician Advisory Committee, Onyx Proctor
Penumbra
3-D Separator Trial Executive Committee
Coaxia
Physician Advisory Committee
Consultant
Rapid Medical
Physician Advisory Committee, Consultant
Intracranial Stenting in AIS:
High Revascularization Rates
Residual “Entrapped Clot” = Risk of Re-occlusion
Stent Implantation Dual Antiplatelet Rx +/- GpIIbIIIa inhibitors =
risk of ICH In-Stent Stenosis
Stent + Retriever = “Stentriever”
Temporary Endovascular Bypass
Thrombus Retrieval
The Anatomy of the Stent-Retrievers
Solitaire™ FR FDA Cleared
Solitaire™ FR - overlapping stent technology (Parametric™ Design) that provides multiple planes of clot contact. Other devices are constructed from a straight cut tube providing only one plane of contact.
Split Design
55 yo F with no PMHx - acute onset of right HP, L gaze deviation, and global aphasia (NIHSS 22). No improvement with IV tPA
ICA-T occlusion – Solitaire 6x30 mm x 1 pass = full reperfusion (TICI 3)
NIHSS dropped from 22 to 0 at discharge.
Solitaire FR™ Thrombectomy
67 y/o m PMHx of HTN, DM, CKD and CHF p/w R MCA syndrome (L HP, neglect, visual field cut; NIHSS = 12) in the setting of new onset Afib
ICA-T occlusion – Solitaire 6x30 mm x 1 pass = full reperfusion (TICI 3)
Solitaire FR™ Thrombectomy
Traditional Strut Orientation is Turned on its Side for Greater Clot Penetration + Retention under Load
Trevo™ RetrieverFDA Cleared
Trevo™ Retriever
Pre-Rx Post-Rx
Baseline NIHSS = 12 → 90-Day NIHSS = 0Baseline mRS = 0 → 90-Day mRS = 1
67 y/o female s/p IV rt-PA without any improvement
Trevo™ Thrombectomy
Trevo™ Thrombectomy
Trevo Provue™
The distal end of the Trevo™* Device extends 10mm past its working length when unconstrained.
40mm (tot. length)
20mm (working length) 6mm 4mm10mm
Proximal marker Distal marker tip
Proximal non working length Distal non working length
Laser cut, tubular design
4mm (≥1.5mm)
32mm (tot. length)
20mm (working length)
Proximal marker
Distal markers (3/4)
Laser cut, open slit design
12mm
Proximal non working length
4mm
Solitaire™ FR Device. Image property of Covidien. Device measurements taken from Solitaire™ FR Device IFU. Document Number 70426
Trevo™* Device. Image property of Covidien. Device measurements taken from Trevo™* Device IFU.
Solitaire FR vs. Trevo Design Overview
Secures Thrombus Easy Delivery Minimizes contact with vessel intima
Penumbra Separator 3-D (Stent-Retriever):*Investigational Device
In U.S. only FDA IDE approved for Clinical Trail and Vessels ≥2.5 mm
85 yo M with a PMHx of DM2, HTN, HLD, CAD s/p PCI, AFIB with pace-maker, off coumadin x 3 yrs p/ w with acute onset of L HP, Left hemineglect, R Gaze Deviation, VF Cut, and dysarthria (NIHSS 21). Treated with IV rt-PA without any improvement
Complete right MCA-M1 occlusion.
Treated with Thrombectomy in the Penumbra 3-D trial with full reperfusion (TICI 3).
Penumbra Separator 3-D (Stent-Retriever):
Stent-Retrievers Randomized Clinical Trials
2 RCTs (TREVO 2 & SWIFT): Stent-Retrievers > Merci
2 RCTs (TREVO 2 & SWIFT): Stent-Retrievers > Merci
EndpointTrevo2 Trevo(n=88)
Trevo2 Merci (n=90)
Trevo2p-value(n=178)
SWIFT Solitaire(n=58)
SWIFT Merci(n=55)
SWIFTp-value(n=113)
Successful Recanalization*
86.4% (76/88)
TICI 2b-367.8%
60.0% (54/ 90)
TICI 2b-343.4%
< 0.000168.5% (37/54)
30.2% (16/53) < 0.0001
mRS 0-2 at 90d** 40.0% (34/85)
21.8% (19/87) 0.0130 36.4%
(20/55)29.2% (14/48) 0.5300
mRS ≥ 2, OR ↓NIHSS ≥ 10 points, OR return to baseline mRS at 90 days
52.9%(45/85)
42.5%(37/87) 0.2218
58.2% (32/55)
33.3% (16/48)
0.0172
Mortality at 90-days33.0% (29/88)
23.6% (21/89) 0.1845
17.2% (10/58)
38.2% (21/55) 0.0196
mRS 0-3 at 90d49.4%
(42/85) 37.9%
(33/87) 0.166356.4%(31/55)
37.4%(18/48) 0.0752
SICH***6.8%
(6/ 88) 8.9%
(8/ 90) 0.78201.7% (1/58)
10.9% (6/55) 0.0566
Nogueira RG et al. Lancet, Aug 2012Saver J et al. Lancet, Aug 2012
2 RCTs (TREVO 2 & SWIFT): Stent-Retrievers > Merci
TREVO 2 SWIFT
Number of Passes with Device
Up to 6 passes with study device. Study device ≥3 passes unless successful.
Up to 3 passes with study device.
Primary Efficacy Endpoint
Successful Recanalization with Study Device
Successful Recanalization with Study Device AND no sICH
Definition of Revascularization
TICI 2a, 2b or 3 (Core Lab 1)
TIMI 2/3 in all treatable vessels (Core Lab 2)
“Roll-In” Phase None2 roll-in patients prior to randomization
Definition of Good Outcome
mRS ≤2mRS ≤2, OR ↓NIHSS ≥ 10 points, OR return to baseline mRS
Baseline mRS Inclusion mRS 0-1 (Evaluator 1) mRS 0-5 (Evaluator 2) [median 0; mean 0.5]
90-day mRS Loss to F/UTrevo: 3%Merci: 3%
Solitaire: 5%Merci: 13%
sICH
(ECASS III) Any apparently extravascular blood in the brain/cranium associated with a ↑ of NIHSS ≥ 4, or death and was identified as the predominant cause of the neurological deterioration. (Core Lab 1)
Any parenchymal hematoma, subarachnoid hemorrhage, or intraventricular hemorrhage associated with a ↑ of NIHSS ≥ 4 within 24hr. (Core Lab 2)
TREVO 2 vs. SWIFT: Baseline Differences
EndpointTrevo2 Trevo(n=88)
Trevo2 Merci (n=90)
Trevo2p-value(n=178)
SWIFT Solitaire(n=58)
SWIFT Merci(n=55)
SWIFTp-value(n=113)
mTrevo2 vs.
mSWIFT
tTrevo2vs.
mSWIFT
sSWIFTvs.
mTrevo2
tTrevo2vs.
sSWIFT
Successful Recanalization*
86.4% (76/88)
TICI 2b-367.8%
60.0% (54/90)
TICI 2b-343.4%
< 0.0001
68.5% (37/54)
30.2% (16/53)
< 0.0001 N/A N/A N/A N/A
mRS 0-2 at 90d** 40.0% (34/85)
21.8% (19/87)
0.013 36.4% (20/55)
29.2% (14/48)
0.530 0.404 0.261 0.082 0.724
mRS ≤ 2, OR ↓NIHSS ≥10 points, OR return to baseline mRS at 90 days
52.9%(45/85)
42.5%(37/87) 0.222
58.2% (32/55)
33.3% (16/48) 0.017 0.358 0.032 0.085 0.603
Mortality at 90-days33.0% (29/88)
23.6% (21/89) 0.184
17.2% (10/58)
38.2% (21/55) 0.020 0.089 0.590 0.412 0.038
Mortality at 30-days 26.1%(23/88)
23.6%(21/90) 0.729 15.5%
(9/58)27.3%(15/55) 0.168 0.692 1.000 0.298 0.155
mRS 0-3 at 90d 49.4%(42/85)
37.9% (33/87)
0.166 56.4%(31/55)
37.4%(18/48)
0.075 1.000 0.208 0.038 0.489
SICH*** 6.8%(6/88)
8.9% (8/90) 0.782 1.7%
(1/58)10.9% (6/55) 0.057 N/A N/A N/A N/A
TREVO 2 vs. SWIFT: Comparisons
Trevo 2SWIFTScientifically Invalid Comparisons!!!!
Note: >400 patients would be needed to demonstrate a difference in TICI 2-3 of 80% vs. 90% (80% Power).>3000 patients for a 90-day mRS 0-2 40% vs. 45%!!!!
Source: http://www.graphpad.com. Fisher's exact test. Two-tailed P value
The Utility of the Merci Device in the Stent-Retriever Era…
Other Stent-Retriever Multicenter Studies
2009 2010 2012 20142011 2013
STAR
SWIFT PRIME
Introduction of Solitaire™
FR to European
market
IMS III
SWIFT
SolitaireRetrospective
TREVO
TREVO II
Stent-Retriever Clinical Studies
Stent-Retriever Studies Design:
Study Design
SWIFT TREVO 2
TREVO STARSolitaire
EU Registry
SolitaireUSA
Registry(NASA)
START
Prospective -- --
Multi-center
Randomized -- -- -- -- --
Enrollment 113 31 roll-in
178 60 202 141 343105(147
enrolled)
Sites18 US
& Europe27 US & 1 EU
7 EU 14 EU, AU, CA
6 EU 24 US 27 US
Independent
Core Lab --
CEC -- -- ?
DSMB -- -- -- -- ?
Stent-Retriever Studies Baseline Characteristics:
Study Design SWIFT TREVO
2 TREVO STARSolitaire
EU Registry
SolitaireUSA
Registry(NASA)
START
Age 67.1 ± 12.0
70.2 (22-86)
65.2 (21-84)
68.4 ± 12.5
66.3 ± 13.1
67.3±15.2
65.7± 14.2
Baseline NIHSS, Median
18 (9-28)
19 (8-29)
18 (8-28)
17(8-26)
18 18(14-23)
19(14-22)
Time from Onset –Groin
(Median, Hr)
4.6 ± 1.4
(mean, 1st DSA)
4.7 (1.6-7.7)
3.2 (1.7-6.7)
3.4(n=185)
5.1
(n=113)
6.1(mean)
5.7(median, onset to
end procedure)
ASPECTS >7
78%(109/139)
50%(83/166)
? High % N/A N/A N/A
Saver J et al. Lancet, Aug 2012; Nogueira RG et al. Lancet, Aug 2012; Wahlgren N , ISC 2012, Pereira VM, ISC 2013; Davalos A, Stroke, Oct 2012; Zaidat O, ISC 2013; Frei D et al. ISC 2013
EndpointSWIFT
Solitaire(n=58)
Trevo2 Trevo
(n=88)
TREVO EU
(n=60)
STAR(n=202)
SolitaireEU
Registry
SolitaireUSA
Registry(NASA)
START(n=105)
Successful Recanalization*
68.5%(37/54)
TIMI 2-3Treatable Vessels
86.4% (76/88)
TICI ≥2a
TICI ≥2b67.8%
90.0%
TICI ≥2a
84.2% (160/190)
TICI ≥2b
85% (120/142)
TICI ≥2b
87.2%(299/343)
TICI ≥2a
85%
TIMI 2-3
mRS 0-2 at 90d** 36.4% (20/55)
40.0% (34/85)
55.0% 57.9%(117/202)
55% (77/141)
41.4%(109/309) 47%
mRS ≥ 2, OR ↓NIHSS ≥ 10 points, OR return to baseline mRS at 90 days
58.2% (32/55)
52.9%(45/85) 72.0% N/A N/A N/A N/A
Mortality at 90-days 17.2% (10/58)
33.0% (29/88)
20.0% 6.9%(14/202)
20%(29/141)
30.4%(94/309)
27%
mRS 0-3 at 90d 56.4%(31/55)
49.4% (42/85) N/A 74% N/A N/A N/A
SICH*** 1.7%(1/58)
6.8%(6/ 88)
5.0% 1.5%(3/202)
4.0% (5/141)
10%(34/341)
11.0%(12/105)
Stent-Retriever Studies Outcomes:
90-Day mRS 0-2: 36-58%
sICH: 1.5-11%
90-Day mRS 6: 7-33%
What We Don’t Know Yet…
Do We Really Need Flow-Control/Balloon Guide Catheter?
THROMBUS RETRIEVAL
Trevo Thrombectomy: Pre-Clinical Data
Nogueira RG et al. J NeuroIntervent Surg 2012;4:295-300
Balloon Guide Catheter
Risk of thromboembolic events
Risk of thromboembolic events
Time consumingRisk of local complicationsIncrease procedural costs
Balloon Guide Catheter
EU SOLITAIRE RETROSPECTIVE STUDY:Correlation b/w univolved territory infarction and
Balloon guide catheter (BGC)
Core Lab controlled
p=0.0009 by Fisher`s exact test
N cases(N=124)
N Infarct % Infarct
With BGC 96 6 6.2%
Without BGC 28 9 32%
Balloon Guide Catheter
Are Stent-Retrievers Superior to Thromboaspiration?
Copyright ©2012 Penumbra, Inc. All rights reserved, 6216 Rev A
Penumbra MAX Technology = Aspiration Power
Data on file. Flow rates of 3MAX, 4MAX and 5MAX using MAX Pump and MAX Aspiration Tubing vs. 032, 041 and 054 using current pump and PST1
5MAX
4MAX
3MAX
054
041032
+83%
+200%
+83%
One Cannot Compare Different Trials!!!!!
Penumbra Ad at JNIS:
Actually Data from the Penumbra START Trial shows Outcomes Varies According to Many Different Predictors:
No Concurrent Comparison of Stentrievers vs. Aspiration!
Clinical, Angiographic, and Radiographic Outcomes Differences Amongst Mechanical Thrombectomy Devices: Initial Experience of a Large-Volume Center
324 Consecutive AIS Patients at Grady Memorial Hospital
37 No clot retrieval (8 intracranial stent only, 16 IA tPA only, 12 angioplasty only, 1 none)
287 Received clot retrieval (115 stent retrieval cases [87 solitaire + 28 Trevo]; 81 MERCI; 91 Penumbra)
Of the 115 stent retrieval (40 IA t-pA adjuvant, 8 penumbra adjuvant, 23 both)
Of the 81 MERCI (5 IA t-PA adjuvant, 15 penumbra adjuvant, 45 both)
Of the 91 Penumbra (68 IA t-PA adjuvant)
Differences Amongst Mechanical Thrombectomy Devices:
Stent Retrieval MERCI Penumbra P value P value P value P value
N=115 N=81 N=91(comparison
of all 3 groups)
(Stent Retriever vs. Penumbra)
(Stent Retriever vs.
Merci)
(Penumbra vs. Merci)
Age, mean (STD)67.4 (+/- 13.7)
65.8 (+/- 14.7)
64.6 (+/- 14.5) 0.365 0.156 0.432 0.590
NIHSS, median (IQR) 18 (15-24) 21 (16-24) 19 (14-22) 0.061 0.805 0.045 0.031Baseline Glucose, mean (STD)
143.4 (+/-53.3)
148.6 (+/-57.0)
146.9 (+/-66.3) 0.817 0.682 0.513 0.850
Reperfusion99 (86%) 57 (70%) 71 (78%) 0.027 0.130 0.007 0.251 Partial (TICI 2b/3), No.
(%)Reperfusion
43 (37.4%) 11 (13.6%) 8 (8.8%) <0.001 <0.001 <0.001 0.317 Complete (TICI 3), No. (%)Functional Outcome N=109 N=81 N=91
0.079 0.479 0.102 0.026mRS 0-2 at 90 days, No. (%)
39 (36%) 20 (25%) 36 (41%)
Infarct Volume, mean (STD)
61.5 (+/- 65.1)
69.5 (+/- 70.2)
59.2 (+/- 52.6)
0.541 0.794 0.423 0.282
Procedure time, mean (STD)
79.3 (+/- 57.1)
90.6 (+/- 43.9)
74.5 (+/- 40.4) 0.086 0.499 0.138 0.013
SICH8 (7%) 6 (7%) 5 (5%) 0.863 0.657 0.917 0.609
PH1, PH2, No. (%)
ASPECTS, median (IQR)N=94 N=67 N=68
0.242 0.101 0.659 0.2437 (6-9) 8 (6-9) 8 (7-9)
Favorable ASPECTS>7, No. (%) 45 (51%) 41 (61%) 42 (62%) 0.124 0.080 0.095 0.946
LKN to GP, median (IQR)279 (212-384)
295 (215-390)
310 (242-474) 0.208 0.080 0.552 0.282
Are Stent-Retrievers Superior to Medical Therapy?
IMS III – Potential Reasons For Lack of Benefit and TREVO2/SWIFT
ASPECTS 8-10
ICA-TMCA-M1
Time to Treatment
TARGET Effective
Devices
SWIFT and TREVO 2 have the highest rates of revascularization and good outcomes (mRS 0-2) seen in randomized AIS thrombectomy trials
SWIFT and TREVO 2 provides Level 1a evidence that the Stent Retrievers are superior to the prior generation of clot retrievers (i.e., Merci Retriever®)
The safety of the Stent Retrievers is established Mortality and SICH rates are within normal range for AIS
Intervention (compared to landmark stroke trials)
Cannot directly compare TREVO 2 vs. SWIFT (vs. Penumbra START and other thrombectomy studies) There are too many differences in trial design and definitions and
patient population
Stent-Retriever +/- Thromboaspiration need to be test against medical therapy in a RCT
Stentrievers Clinical DataConclusions
Thank you for your attention!
Regeneracion, Pasajes Neuronales, 2006