Mechanical thrombectomy in Plymouth Will Adams 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
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 40.0% 30.0% 32.6% 20.0% 19.1% 10.0% 0.0% 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
14 Derriford Thrombectomy Activity 29 patients 12 10 8 6 4 2 0 2013 2014 2015 2016 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
100 90 80 70 60 50 40 30 20 10 0 Age (mean 61) 1 3 5 7 9 11 13 15 17 19 21 23 25 27 29 Age
Ictus to puncture Picture to puncture 18 12 6 1 4 7 10 13 16 19 22 25 28
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 12 10 8 6 4 2 0 0 1 2a 2b 3
a direct aspiration first pass technique (ADAPT) https://www.youtube.com/watch?v=shddd8vs8fe&feature=player_embedded
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