• Will Adams

Mechanical thrombectomy in Plymouth Will Adams

History Intra-arterial intervention

• 1995 (NINDS) iv tPA – improved clinical outcome in patients treated within 3 hours of ictus but limited recanalisation (1)

• 1995 – time window extended to 4.5 hours with ECASS study (2)

• 2005 MERCI trial – improved recanalisation in occlusion resistant to iv tPA (3)

• 2013 – IMS III, SYNTHESIS and MR RESCUE showed equivocal results when compared to iv tPA alone (4)

1. The National Institute of Neurological Disorders and Stroke rt-PA Stroke Study Group. Tissue plasminogen activator for acute ischemic stroke. N Engl J Med 1995;333:1581-1587 2. Intravenous thrombolysis with recombinant tissue plasminogen activator for acute hemispheric stroke. The European Cooperative Acute Stroke Study (ECASS)Hacke W et al. JAMA. 1995;274(13):1017-25.

3. Safety and efficacy of mechanical embolectomy in acute ischemic stroke: results of the MERCI trial. Smith WS et al. MERCI Trial Investigators Stroke. 2005;36(7):1432-8.

4. Endovascular therapy after intravenous t-PA versus t-PA alone for stroke. Broderick JP et al. Interventional Management of Stroke (IMS) III Investigators N Engl J Med. 2013;368(10):893-903.

• iv tPA administered within 4.5 hours after the onset of acute ischaemic stroke improves outcomes.

• BUT - unresponsiveness of large thrombi to rapid enzymatic digestion, a narrow time window for administration, and the risk of cerebral and systemic haemorrhage.

• Among patients with occlusions of the intracranial internal carotid artery or the first segment of the middle cerebral artery (or both), iv tPA results in early reperfusion in only 13 to 50%.

NICE (2013) made the following recommendations:

• patients who are suitable for thrombolysis and satisfy the criteria for a research study (e.g. Pragmatic Ischaemic Stroke Thrombectomy Evaluation-PISTE) should be considered for enrolment into a randomised controlled trial

• patients for whom thrombolysis has failed or is unsuitable due to contraindications can be considered for thrombectomy if not eligible for a trial.

Summary of the Five Positive Randomized Controlled Studies 2015 – mechanical thrombectomy is effective.

• MR CLEAN

• ESCAPE

• EXTEND – IA

• SWIFT PRIME

• REVASCAT

• (PISTE)

How do these trials differ from IMS-III?

- Required CTA confirmation of LVO

- Used available modern technology

– Stent retrievers and direct aspiration with Penumbra catheters

6

Summary of the Five Positive Randomized Controlled Studies

• MR CLEAN (Multicentre Randomized Clinical Trial of Endovascular Treatment for Acute Ischemic Stroke in the Netherlands)

• RCT: IV tPA vs IV tPA + IA Therapy • 500 randomized patients • 12/10 – 3/14 enrollment • Open label • Key inclusion criteria

– NIHSS ≥ 2

– Anterior circulation LVO confirmed by CTA

– IA treatment initiated within 6 hours from onset

• Primary Outcome: mRS score at 90 days

MR CLEAN – Primary Outcome

• 32.6% of the interventional group compared to 19.1% of the standard therapy group achieved a mRS score of 0-2 (p < 0.01), numbers needed to be treated 8.

MR CLEAN – Secondary Outcome - higher odds of achieving functional independence in

favour of intervention

32.6%

19.1%

0.0%

10.0%

20.0%

30.0%

40.0%

Intervention Control

Summary of the Five Positive Randomized Controlled Studies

• ESCAPE NEJM 2015 – terminated early after interim analysis following MR CLEAN

• 22 centres worldwide, 316 participants enrolled, 238 received iv alteplase (120 in the intervention group and 118 in the control group).

• proximal intracranial occlusion in the anterior circulation were included up to 12 hours after symptom onset. Large infarct core or poor collateral circulation on CT and CT angiography were excluded

• Solitaire stent in 86.7% of interventional cohort

ESCAPE

• 53% of the intervention group compared to 29.3% of the control group had a favourable outcome (mRS ≤2; p < 0.001).

EXTEND IA Trial (Extending the Time for Thrombolysis in Emergency Neurological Deficits with Intra-Arterial Therapy) NEJM 2015

• Prematurely halted after 70 patients

• less than 4.5 hours after the onset of ischaemic stroke either to undergo endovascular thrombectomy with the Solitaire FR stent retriever or to continue receiving alteplase alone.

• All the patients had occlusion of the internal carotid or middle cerebral artery and evidence of salvageable brain tissue and ischemic core of less than 70 ml on CT perfusion imaging.

• Endovascular therapy initiated at a median of 210 minutes after the onset of stroke

EXTEND IA

• improved functional outcome at 90 days, with more patients achieving functional independence (score of 0 to 2 on the mRS, 71% vs. 40%; P=0.01

Swift Prime Trial design

• RCT: IV tPA vs IV tPA + IA Therapy

• 196 randomized patients

• 12/12 – 11/14 enrollment

• Key inclusion criteria

– NIHSS ≥ 8

– Ages 18 - 80

– Anterior circulation LVO confirmed by CTA

– ASPECTS ≥ 7

– IA treatment initiated < 6 hours from onset

• Primary Outcome: mRS at 90 days

SWIFT PRIME Trial (Solitaire with the Intention for Thrombectomy as Primary Treatment for Acute Ischemic Stroke) • SWIFT PRIME used Solitaire FR and Solitaire 2 devices in

89% of their cohort. The study was ceased by the data and safety monitoring board after an interim review found a substantial benefit for patients treated in the intervention arm.

• The study recruited 196 patients and measured IV t-PA and neurovascular thrombectomy against IV t-PA alone. The interventional group, compared to the control, achieved favourable outcomes (mRS 0-2) at 60 and 35%, respectively [adjusted OR 2.03 (95% CI 1.36-3.03). An mRS shift was seen in 1 patient for every 2.6 patients treated. There was no statistical difference in sICH (p = 0.50) or mortality (p = 0.12).

SWIFT PRIME Trial

REVASCAT

• REVASCAT was ceased early after the publications of ESCAPE, EXTEND IA and MR CLEAN resulted in a loss of equipoise.

• Intervention led to a 1-point mRS improvement to the adjusted OR 1.7 (95% CI 1.05-2.8). When comparing the intervention group with the control group, the proportion of patients achieving independent functional outcome (mRS 0-2) was 43.7 versus 28.2% [adjusted OR 2.1 (95% CI 1.1-4.0)]. NNTB was 6.5 to prevent disability or death. No statistically significant difference was found in mortality or sICH when comparing the two groups.

REVASCAT

Pragmatic Ischaemic Stroke Thrombectomy Evaluation

Primary outcome day 90 mRS

• Exeter 47.9 m; 53 min

• Exeter 47.9 m; 53 min • NDDH 59 m; 1 hr 46 min

• Exeter 47.9 m; 53 min • NDDH 59 m; 1 hr 46 min • Torbay 41.5 m; 47 min

• Exeter 47.9 m; 53 min • NDDH 59 m; 1 hr 46 min • Torbay 41.5 m; 47 min • Truro 56.4 m; 1 hr 18 min

0

2

4

6

8

10

12

14

2013 2014 2015 2016

Derriford Thrombectomy Activity – 29 patients

“… in the absence of this service being commissioned I am not sure we should be treating patients …”

Demographic details

29 patients

Age (mean) 61

M 18 F 11

Referring Trust

Plymouth 24

Exeter 1

Torbay 2

Truro 1

Barnstaple 1

Vessel

Basilar 13

MCA 11

ICA 3

Carotid T 2

0

10

20

30

40

50

60

70

80

90

100

1 3 5 7 9 11 13 15 17 19 21 23 25 27 29

Age (mean 61)

Age

1 4 7 10 13 16 19 22 25 28

Ictus to puncture

Picture to puncture

12

6

18

0

2

4

6

8

10

12

0

1

2a

2b

3

Age TICI pre TICI post

47 0 2a

29 0 1

41 0 2a

68 1 2a

63 0 0

50 0 3

76 0 3

46 0 3

57 0 0

56 0 2b

51 0 0

61 0 0

75 0 0

50 0 0

58 0 0

44 0 3

78 0 1

73 0 0

79 0 2b

50 0 3

51 1 3

87 0 0

76 0 0

62 0 2b

74 0 2a

35 0 3

84 1 2a

84 0 0

64 2a 3

https://www.youtube.com/watch?v=SHDDD8Vs8fE&feature=player_embedded

a direct aspiration first pass technique (ADAPT)

• Selection of patients for mechanical clot retrieval for treating acute ischaemic stroke should be done by clinicians experienced in the use of thrombolysis for stroke and in interpretation of relevant imaging.

• The procedure should only be carried out by appropriately trained specialists with regular experience in intracranial endovascular interventions, with appropriate facilities and neuroscience support.

“I consider a reasonable target is for England to have a properly resourced country-wide 24/7 mechanical thrombectomy service by 2020.

Quite where the manpower will come from is still unclear. If reasonable rotas of 1:5 or 1:6 are to be achieved in the majority of Neuroscience centres, there is likely to be a shortfall of 80-90 neurointerventionists”.

Norman McConachie

Chair UK NeuroInterventional Group