Endovascular treatment for ischemic stroke: state of the art

Jens Fiehler Klinik für Neuroradiologische Diagnostik und Intervention

Universitätsklinikum Hamburg-Eppendorf, Hamburg, Germany

fiehler@uke.de

Speaker for Consultant for Bayer Healthcare Acandis Boehringer Ingelheim Codman Covidien Microvention Penumbra Sequent Philips Stryker Siemens

2

H. Zeumer 1978

Background: 1978: how it all began …

1995: NINDS

Study

I.V. tPA effective!

Lees K et al, Lancet 2010; 375: 1695–703 Mean NIH-SS score: 11 (IQR7–16)

Therapy effect of i.v. tPA?

8%↓ mRS 0-2 (d90)

11%↓ mRS 0-2 (d90)

6%↓ mRS 0-2 (d90)

Kein Effekt

New „curreny“: one tPA = 8% ARR

MCA-branchMCA-truncCTOICA&MCA

400

300

200

100

0

ADC lesion <6 hours

Infarct (day 5-8)

MCA-branchMCA-truncCTOICA&MCA

400

300

200

100

0

ADC lesion <6 hours

Infarct (day 5-8)

*

Lesion volumes vs. occlusion types

mL

Fiehler et al. AJNR Am J Neuroradiol 26:1056–1061, 2005

IV recanalisation – occlusion site (n=120)

Mechanical Recanalisation

Mechanical Recanalisation

0%

10%

20%

30%

40%

50%

60%

70%

80%

90%

100%

30% 40% 50% 60% 70% 80% 90% 100%

Castano C, et al. Stroke. 2010;41:1836-1840, Nayak S, et al. Br J Radiol. 2010;83:1017-1022, Venker C, et al. Fortschr Neurol Psychiatr.

2010;78:652-657, Cohen JE, et al. Stroke. 2011;42:1929-1935, Mendonca N, F et al. 2011, Miteff F, et al. AJNR Am J Neuroradiol.

2011;32:1078-1081, Park H, et al. J Neurointerv Surg. 2011, Rohde S, et al. Stroke. 2011;41:2559-2567, Stampfl S, et al. Interv Neuroradiol.

2011;17:235-240, Cohen JE, et al. J Clin Neurosci. 2012;19:39-43, Machi P, et al. J Neurointerv Surg. 2012;4:62-66, Mohlenbruch M, et al.

Clin Neuroradiol. 2012, Mpotsaris A, et al. J Neurol Neurosurg Psychiatry. 2012;83:117-118, Broderick, JP et al. IMS III Feb 7, 2013, NEJM,

TREVO2, SWIFT, NASA, STAR

mR

S≤2

(%)

Recanalisation rate (%)

Recanalisation and clinical result

Ribo M et al. Stroke. 2011;42:3465-3469. Goyal, M et al. Stroke 2010;42(1):93–7.

Clinical outcome – late recanalisation (>5h)

Small infarcts Good Collaterals

+27.6% +40.9%

0% 10% 20% 30% 40% 50% 60% 70% 80% 90% 100%

i.v. lysis (n=20, 2nk)

stent retriever (n=21) 0

1

2

3

4

5 to 6

57%

28%

Jerusel, N et al. 2014, submitted

Own experiences in Carotid-T-occlusions (mRS 0-3)

ARR lower 95%

upper 95%

29.4% -0.2 59

0%

10%

20%

30%

40%

50%

60%

70%

80%

90%

100%

30% 40% 50% 60% 70% 80% 90% 100%

Castano C, et al. Stroke. 2010;41:1836-1840, Nayak S, et al. Br J Radiol. 2010;83:1017-1022, Venker C, et al. Fortschr Neurol Psychiatr.

2010;78:652-657, Cohen JE, et al. Stroke. 2011;42:1929-1935, Mendonca N, F et al. 2011, Miteff F, et al. AJNR Am J Neuroradiol.

2011;32:1078-1081, Park H, et al. J Neurointerv Surg. 2011, Rohde S, et al. Stroke. 2011;41:2559-2567, Stampfl S, et al. Interv Neuroradiol.

2011;17:235-240, Cohen JE, et al. J Clin Neurosci. 2012;19:39-43, Machi P, et al. J Neurointerv Surg. 2012;4:62-66, Mohlenbruch M, et al.

Clin Neuroradiol. 2012, Mpotsaris A, et al. J Neurol Neurosurg Psychiatry. 2012;83:117-118, Broderick, JP et al. IMS III Feb 7, 2013, NEJM,

TREVO2, SWIFT, NASA, STAR

mR

S≤2

(%)

Recanalisation rate (%)

Recanalisation and clinical result

0%

10%

20%

30%

40%

50%

60%

70%

80%

90%

100%

30% 40% 50% 60% 70% 80% 90% 100%

Castano C, et al. Stroke. 2010;41:1836-1840, Nayak S, et al. Br J Radiol. 2010;83:1017-1022, Venker C, et al. Fortschr Neurol Psychiatr.

2010;78:652-657, Cohen JE, et al. Stroke. 2011;42:1929-1935, Mendonca N, F et al. 2011, Miteff F, et al. AJNR Am J Neuroradiol.

2011;32:1078-1081, Park H, et al. J Neurointerv Surg. 2011, Rohde S, et al. Stroke. 2011;41:2559-2567, Stampfl S, et al. Interv Neuroradiol.

2011;17:235-240, Cohen JE, et al. J Clin Neurosci. 2012;19:39-43, Machi P, et al. J Neurointerv Surg. 2012;4:62-66, Mohlenbruch M, et al.

Clin Neuroradiol. 2012, Mpotsaris A, et al. J Neurol Neurosurg Psychiatry. 2012;83:117-118, Broderick, JP et al. IMS III Feb 7, 2013, NEJM,

TREVO2, SWIFT, NASA, STAR

mR

S≤2

(%)

Recanalisation rate (%)

TREVO2

SWIFT

NASA

STAR

IMS3

Recanalisation and clinical result

Saver J et al. Lancet 2012; 380: 1241–49

Broderick, JP et al. IMS III, 2013, at NEJM.org

43%

40%

28%

37%

22%

40%

IMS 3

TREVO 2

SWIFT

IMS3 430/434 IA patients (99%) treated with MERCI, IA

tPA, Penumbra or sth. old-fashioned

SYNTHSIS EXP catastrophic design faults, 142/165 of IA patients

(86%) treated with sth. old-fashioned

MR RESCUE design faults,, 70/70 der IA patients (100%)

treated with sth. old-fashioned

in these studies: only 4% Stenttriever

?

NEJM-Triplett of Feb 2013

Broderick, JP et al. IMS III, Ciccone, A et al., SYNTHESIS Expansion, Kidwell, C et al. MR RESCUE published on February 7, 2013, at NEJM.org

Recanalisation vs. outcome (ACI, M1-Occlusion)

TICI0 TICI1 TICI2a TICI2b TICI3

n= 32 n= 16 n= 67 n= 80 n= 5

% 90 Day

mRS 0-2

3.1% 12.5% 19.4% 46.3% 80%

6.3% 35.5% p <

.0001

13.9% 48.2% p <

.0001

From Tomsick, IMS3 presentation, ISC-2013

0%

10%

20%

30%

40%

50%

60%

70%

80%

90%

TICI=0 TICI=1 TICI=2a TICI=2b TICI=3

+26,9 %

TICI 2a is not enough!

43%

Castano C, et al. Stroke. 2010;41:1836-1840, Nayak S, et al. Br J Radiol. 2010;83:1017-1022, Venker C, et al. Fortschr Neurol Psychiatr.

2010;78:652-657, Cohen JE, et al. Stroke. 2011;42:1929-1935, Mendonca N, F et al. 2011, Miteff F, et al. AJNR Am J Neuroradiol.

2011;32:1078-1081, Park H, et al. J Neurointerv Surg. 2011, Rohde S, et al. Stroke. 2011;41:2559-2567, Stampfl S, et al. Interv Neuroradiol.

2011;17:235-240, Cohen JE, et al. J Clin Neurosci. 2012;19:39-43, Machi P, et al. J Neurointerv Surg. 2012;4:62-66, Mohlenbruch M, et al.

Clin Neuroradiol. 2012, Mpotsaris A, et al. J Neurol Neurosurg Psychiatry. 2012;83:117-118, Broderick, JP et al. IMS III Feb 7, 2013, NEJM,

TREVO2, SWIFT, NASA, STAR

Recanalisation rate (%)

0%

10%

20%

30%

40%

50%

60%

70%

80%

90%

100%

30% 40% 50% 60% 70% 80% 90% 100%

mR

S≤2

(%)

TREVO2

SWIFT

NASA

STAR

IMS3

Recanalisation and clinical result

Menon et al. Stroke. 2014;45:2024-2029.

IMS3 vs. STAR – 90 Minutes faster management!

-30 Min -65 Min

Final multivariate model

Variable Risk Ratio 95% Confidence Interval

p-value

Time to Reperfusion (every 30 minute delay)

0.90 0.82-0.99 0.02

Baseline ASPECTS 5-10 3.70 1.25-11.00 0.01

Lack of Premorbid Disability

2.61 1.05-6.50 0.01

NIHSS 8-19 (vs ≥20) 1.64 1.07-2.51 0.01

From Khatri, IMS3 presentation, ISC-2013

Menon et al. Stroke. 2014;45:2024-2029.

Time matters also for stenttriever therapy

Menon et al. Stroke. 2014;45:2024-2029.

What predicts good outcome?

http://clinicaltrials.gov

Ongoing acute stroke studies …

• 17 RCTs running (that we are aware of)

• Total number of enrolled patients: 1905

• Total number (expected number): 8455

Ongoing acute stroke studies in MT

eligible ineligible non-responder 1 MR CLEAN Ned/EU 0-6h yes yes yes 2 ANSTROKE Sweden 0-8h yes yes yes 3 ESCAPE Calgary 0-12h yes yes no 4 EXTEND-IA Australia 0-4.5h yes no no 5 PISTE UK 0-4.5h yes no no 6 RESTORE China 0-4.5h yes no no 7 SWIFT-PRIME USA/EU 0-4.5h yes no no 8 THERAPY USA/EU 0-4.5h yes no no 9 SIESTA Heidelberg 0-6h yes no no

10 THRACE France 0-4.5h yes no no 11 SITS-OPEN EU 0-4.5h yes no no 12 DAWN USA/EU 0-24h no yes yes 13 REVASCAT Catalonia 0-8h no yes yes 14 POSITIVE USA 0-12h no yes no 15 THRILL GER/AUT 0-8h no yes no 16 BASICS Ned/EU 4,5-6h no yes no 17 RESILENT Brazil 0-6h no yes no

12/5 9/8 4/13

Target population (vs. IV)

IIT IV IV+MT MT BMT 1 MR CLEAN Ned/EU 0-6h yes yes yes yes yes 2 ANSTROKE Sweden 0-8h yes no yes yes no 3 ESCAPE Calgary 0-12h yes yes yes yes yes

4 EXTEND-IA Australia 0-4.5h yes yes yes no no

5 PISTE UK 0-4.5h yes yes yes no no

6 RESTORE China 0-4.5h yes yes yes no no

7 SWIFT-PRIME USA/EU 0-4.5h no yes yes no no

8 THERAPY USA/EU 0-4.5h no yes yes no no 9 SIESTA Heidelberg 0-6h yes no yes no no

10 THRACE France 0-4.5h yes yes yes no no

11 SITS-OPEN EU 0-4.5h yes yes yes no no 12 DAWN USA/EU 0-24h no yes yes yes yes 13 REVASCAT Catalonia 0-8h yes yes yes yes yes 14 POSITIVE USA 0-12h yes no no yes yes 15 THRILL GER/AUT 0-8h yes no no yes yes 16 BASICS Ned/EU 4,5-6h yes yes yes no no 17 RESILENT Brazil 0-6h yes yes yes yes yes

14 13 15 8 7

Target population (vs. IV)

FPI Months enrolling LPA (exp)

Remaining Months Projected LPA

SIESTA Heidelberg 0-6h 01.08.14 3 01.01.16 11,8 6 11.04.15 EXTEND-IA Australia 0-4.5h 01.08.12 24 - 2,9 11 02.09.15 THRACE France 0-4.5h 01.06.10 50 31.08.15 7,8 11 10.09.15 ESCAPE Calgary 0-12h 01.02.13 18 01.04.15 17,0 12 02.10.15 ANSTROKE Sweden 0-8h 14.11.13 8 - 3,0 21 16.07.16 REVASCAT Catalonia 0-8h 01.11.12 21 ? 9,1 55 27.04.19 SWIFT-PRIME USA/EU 0-4.5h 14.01.13 18 - 10,0 65 20.02.20 SITS-OPEN EU 0-4.5h 21.03.14 4 30.10.16 5,3 109 10.10.23 PISTE UK 0-4.5h 01.04.13 16 01.04.17 2,9 142 12.06.26 THERAPY USA/EU 0-4.5h 10.03.12 29 ? 3,7 160 14.12.27 DAWN USA/EU 0-24h 28.09.14 1 01.07.17 1,7 299 20.05.39 THRILL GER/AUT 0-8h 01.05.14 3 30.03.18 1,5 387 11.08.46 BASICS Ned/EU 4,5-6h 15.04.11 40 ? 1,0 743 01.11.75 POSITIVE USA 0-12h 01.09.13 11 01.05.16 ? ? ? MR CLEAN Ned/EU 0-6h 01.12.10 44 01.07.14 11,3 0 RESILENT Brazil 0-6h 01.01.15 0 01.01.18 ? ? ? RESTORE China 0-4.5h 01.09.13 11 01.11.15 ? ? ?

Linear projection of LPA

0

100

200

300

400

500

600

700

800

900

remaining

enrolled

Enrolment status (October 2014)

final halted halted

MR CLEAN

Dippel, D. et al. 9th World Stroke Congress, 24 October 2014

• Patients (18 years or older) acute ischemic stroke of the anterior circulation. IA treatment within 6h from symptom onset.

• The intervention and control groups - well balanced: age, sex, average NIHSS scores 17 and 18

• Equivalent occlusion sites (30% CTO, 61% to 66% in the M1, < 10% in the

M2 segment, <1% in the A1/A2)

• OTT to IV (85 - 87 min) and time to randomization (196 to 204 min)

• Endovascular treatment involved retrievable stents in 97% of the cases.

• The time from onset to groin puncture: 260 minutes.

3

0

9

6

21

13

18

16

22

30

6

12

21

22

0% 20% 40% 60% 80% 100%

1

2

MR CLEAN

19%

33%

IV in % (n = 267)

IV + IA in % (n =233)

adjusted OR 1.67 (95% CI, 1.21 to 2.30) absolute risk reduction for poor outcome 14% (mRS 3-6)

mRS (90d)

Dippel, D. et al. 9th World Stroke Congress, 24 October 2014

MR CLEAN

Dippel, D. et al. 9th World Stroke Congress, 24 October 2014

• MT more beneficial >80 years. The adjusted OR 1.60 (95% CI, 1.13 to 2.27) for patients <80 years of age and 3.24 (95% CI, 1.21 to 8.62) for those 80 or older.

• NIHSS score, the intervention was not statistically better for lower scores

(2 to 15 or 16 to 19), significantly better for the most severe strokes (20 or greater; adjusted odds ratio, 1.85; 95% CI, 1.06 2.31).

• The intervention was also better if the time from stroke onset to randomization was 120 minutes or longer but not for shorter intervals.

• It was also significantly better if IV alteplase was given but not if alteplase was withheld.

Hamburg: 1.8 Mio

Mechanical Recanalisation in Hamburg?

Center of treatment

Patient‘s symptoms

Time-to microcathether dependent only on

A+B+C: same neurointerventional staff

Time: 3,5 h to microcatheter

147168

125

167

218

164

0

50

100

150

200

250

300

350

400

A B C

CT-MC

O-CT

51 Min 54 Min

Min

Interventional neuroradiology in GER

Map was developed by the BDNR

Sponsored by Codman

Conclusion

• Since 2008: stenttriver is vastly superior to IA lysis

• IV vs. IV+IA RCTs: 1:3 (but 1:0 if Stenttriver only)

• 1905 Patients enrolled in 17 RCTs, almost each one unique

• Need to wait for at least one more positive study

Looking forward to a bright future …