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