Dr Dipankar Dutta discusses some important aspects of mechanical thrombectomy and implications for the NHS and primary care clinicians and commissioners

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Dr Dipankar Dutta

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Read this article to learn more about:

  • the effectiveness of mechanical thrombectomy (MT) in certain types of acute ischaemic stroke
  • NHS England’s commissioning policy for MT and implications for service provision
  • patient selection and pathways.

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Stroke remains the second highest cause of death worldwide and a major cause of disability.1 The cost of stroke to the NHS in England is estimated to be around £3 billion per year, within a wider economic cost of about £8 billion.2

About 85% of strokes are ischaemic and most are caused by arterial thrombosis or embolism with resultant loss of neurological function.3 Over one-third of acute ischaemic strokes (AIS) are caused by large artery occlusion (LAO).4 Large artery occlusion refers to occlusion of the terminal part of the internal carotid artery, the proximal middle cerebral artery (MCA), or basilar artery.5 The previous gold-standard treatment, intravenous alteplase, was successful in lysing large clots responsible for LAO in less than 30% of cases and leading to good clinical outcomes in only about 25% of such patients.5,6 In addition, the use of intravenous (IV) thrombolysis was often limited by delayed patient presentation or other contraindications such as wake-up strokes, patient on anticoagulants, recent surgery, or bleeding. Mechanical thrombectomy (MT) aims to remove the obstructing blood clot from arteries within the brain directly by introducing a clot retrieval device delivered via an intravascular catheter, thereby restoring blood flow and minimising tissue damage. It has several advantages over IV clot lysis including greater efficacy, a larger treatment window, and it can be performed in patients with some contraindications to IV thrombolysis.3,4

This article aims to summarise important aspects of MT for primary care physicians and to discuss its implications for the NHS and commissioners.

Procedure and setting for mechanical thrombectomy

Mechanical thrombectomy can only be carried out in tertiary stroke centres by neurointerventionists, usually interventional neuroradiologists (although other groups also perform this procedure). NHS England has issued commissioning guidance; all thrombectomy centres must be recognised by NHS England as one of their listed centres for this procedure, meet their service specifications, and have regard to the British Association of Stroke Physicians (BASP) Standards for providing safe acute ischaemic stroke thrombectomy services.3,4 The BASP defines a suitable centre as a neuroscience centre incorporating hyperacute stroke units (HASU) embedded within a high quality comprehensive stroke service with access to neurosurgical, neurocritical care and specialist stroke services.4 All centres must enter details about patients admitted with stroke on to the Sentinel Stroke National Audit Programme (SSNAP) database, which is used to audit stroke treatment and outcomes.3

Most patients also have initial treatment with intravenous thrombolysis if they are within the time window and there are no contraindications (see Figure 1).6 NICE interventional procedures guidance (IPG) 548 on Mechanical clot retrieval for treating acute ischaemic stroke7 summarises the procedure; it is usually done under sedation but general anaesthesia is often needed in patients with a reduced level of consciousness or who are uncooperative or agitated.4 Cerebral angiography is done to show the exact location of the arterial occlusion. A delivery catheter is inserted, usually through the femoral artery in the groin, and advanced into the occluded artery using X-ray guidance. A clot-retrieval device attached to a guidewire is introduced through the delivery catheter to the site of the occlusion, to remove the clot and re-establish blood flow. The devices in current use are stent retriever devices sometimes with balloon guide catheters for flow occlusion (to reduce forward flow thereby reducing the chance of distal embolisation), direct aspiration catheters, or combined stent retrievers/aspiration catheters.6,7 Acceptable standards are considered to be groin puncture time to start of revascularisation of <45 minutes in at least 65% of patients and end of revascularisation in a time of median ≤60 minutes.4

Figure showing patient management algorithm for acute stroke and mechanical thrombectomy

Figure 1: Patient management algorithm for acute stroke and mechanical thrombectomy

ED=emergency department; IV=intravenous; MT=mechanical thrombectomy; TIA=transient ischaemic attack; CT=computerisedtomography; LAO=large artery occlusion; HASU=hyper-acute stroke unit; ITU=intensive therapy unit

Patient selection and pathways

Patient selection is usually made jointly between stroke physicians and neurointerventionists.6 Depending on stroke service configurations in different regions, patients may present directly to a tertiary centre. This has been called the ‘mothership’ model and is clearly the most efficient pathway in ensuring timely treatment.6,8 However, geographical constraints may make this impossible and patients may present initially to a peripheral centre where they are assessed and transferred to a tertiary centre while receiving IV tissue plasminogen activator (tPa) prior to thrombectomy. This has been called the ‘drip and ship’ model.6,8 Communication between centres has to include telephone contact and viewing of images remotely via a picture archiving and communication system (PACS). The assessment has to be rapid but thorough and consists of stroke diagnosis, likely localisation, assessment of severity, pre-stroke functional status, and co-morbidities.6 Stroke severity is assessed by the National Institutes of Health Stroke Scale (NIHSS) and pre-stroke functional status by the modified Rankin Scale (mRS).9,10 Urgent vascular imaging, typically plain CT and CT angiogram to confirm LAO prior to consideration of thrombectomy, is required. In addition, the scans are useful for assessment of the collateral circulation (patients with poor collaterals have poorer outcomes) and early ischaemic changes using the Alberta Stroke Programme Early CT Score (ASPECTS).11 Poorer outcomes are likely if the ASPECTS score indicates extensive early ischaemic changes.6,11 See Table 1 for patient selection criteria based on the National clinical guideline for stroke (5th edition; 2016).12 A patient management algorithm is shown in Figure 1. The procedure remains very time-dependent; for every 15 minutes saved in reperfusion, an estimated 39 patients per 1000 treated would be less disabled at 3 months, including 25 more who would achieve functional independence.13

Once the procedure is complete, the patient will need to be monitored in the hyperacute stroke unit (HASU) or neurocritical care of the tertiary centre. In the author’s experience, most patients will require repatriation to their parent hospitals for ongoing rehabilitation and some may be suitable for early discharge, often with the help of the early supported discharge team (ESDT).

Table 1: Patient selection criteria for mechanical thrombectomy6,12
FactorCriteria

Age

No upper age limit if functional status is good

Stroke severity

NIHSS scale ≥6 (moderate severity or above)

CT angiogram

LAO confirmed (proximal MCA, ICA terminus, or basilar); good collaterals

Plain CT

ASPECTS score >5 (absence of extensive early ischaemic changes); exclusion of haemorrhage or other pathology that can explain the symptoms

Pre stroke functional status

mRS score ≤2 (no disability to slight disability)

Time window

Within 6 hours for the anterior circulation; may be longer in selected cases; may be up to 24 hours in the posterior circulation (basilar)

NIHSS=National Institutes of Health Stroke Scale; CT=computerised tomography; LAO=large artery occlusion; MCA=middle cerebral artery;  ICA=internal carotid artery; ASPECTS=Alberta Stroke Programme Early CT Score; mRS=modified Rankin Scale

Evidence base

The national stroke guideline 201612 concluded that mechanical thrombectomy (MT) is an effective acute treatment for selected patients with proximal LAOs as an adjunct to IV thrombolysis, and a standalone treatment for those patients with contraindications to IV thrombolysis.12 Similarly, NICE has reviewed the evidence and issued an interventional procedures guidance (IPG548) recommending MT.7

The efficacy of MT has been confirmed in nine randomised controlled trials (RCTs).6,14–22 After several years of anecdotal reports and a few disappointing early RCTs (these had used first-generation clot retrieval devices and suffered from poor patient selection and delays to treatment), five positive RCTs were published in quick succession starting with the Multicenter Randomised Clinical Trial of Endovascular Treatment for Acute Ischaemic Stroke in the Netherlands (MR CLEAN) in 2014.14 After the positive results of MR CLEAN, many subsequent RCTs were stopped early with a possible detrimental effect on their reliability.6 Most patients received IV alteplase in the control arms of five studies.14–18 Systematic reviews and meta-analyses have enabled more precise estimates of treatment effects as these trials were individually moderate in size with under-representation of patient groups in individual trials. The HERMES collaboration presented patient level data for 1287 patients (634 assigned to endovascular thrombectomy, 653 assigned to usual treatment that included intravenous tPa in 87%).23 Endovascular thrombectomy led to significantly reduced disability at 90 days compared with control (adjusted common odds ratio [cOR] 2.49, 95% confidence interval [CI] 1.76–3.53; p<0.0001).23 The number needed to treat with endovascular thrombectomy to reduce disability by at least one level on mRS for one patient was 2.6.23 The benefits of mechanical thrombectomy over usual care were present in patients aged 80 years or older, those randomised more than 300 min after symptom onset, and those not eligible for intravenous alteplase.23 Mortality at 90 days and risk of symptomatic intracranial haemorrhage did not differ between groups.23 Other meta-analyses have presented very similar conclusions; number needed to treat (NNT) to reduce disability of 2.5, and NNT for an extra patient to achieve independent outcome of 4.25 (3.29–5.99).24,25

Complications of mechanical thrombectomy

The overall complications rate of mechanical thrombectomy is about 4 to 29%, based on recent trial data.6,26 However, many complications are minor and do not affect the eventual outcomes for patients.6 Serious complications include vessel perforation (0.9 to 4.9%), arterial dissection (3%), emboli to new territories (6%), symptomatic intracranial haemorrhage (4.3%), and subarachnoid haemorrhage (2.5%).6,26,27 Vasospasm and vascular access site complications (including dissection, pseudoaneurysm formation, retroperitoneal haematoma, and infection) are other potential complications.6,26

Role of primary care clinicians in thrombectomy

As with other medical emergencies, primary care physicians may encounter patients with suspected acute strokes within the treatment time window. These patients will have to be directed to their nearest stroke centre via 999.28 An algorithm for acute stroke management is shown in Figure 1.

The subsequent management of post-thrombectomy patients is the same as for any other ischaemic stroke. There are no special requirements for antiplatelet or other secondary prevention medication. Primary care has a major role in ongoing secondary prevention as with any other stroke.28

Barriers to the implementation of mechanical thrombectomy

Given the complex and time-dependent nature of MT, there are major challenges to the implementation of MT in the UK and other parts of the world. There are obvious geographical, organisational, and financial barriers to providing a round-the-clock service.29 The most significant problem is probably the lack of trained neurointerventionists; in 2017, there were about 80 such specialists in the UK and 24 neuroscience centres in England.30 There will be significant difficulties in training neurointerventionists and the British Society of Neuroradiologists (BSNR) has issued recommendations on training and suggested training numbers and competencies.31 It has been suggested that given appropriate training, other groups (general interventional radiologists, cardiologists, stroke physicians, or neurologists) may be able to support neurointerventionists.30 Numbers will have to be high enough to support 24/7 rotas covering 365 days a year.

At present, at least one centre in the UK is running such a rota and other existing, within hours, services are in the process of expanding their coverage. Where ‘drip and ship’ is the only possible model, staff such as radiographers (with the training to perform CT angiograms) in the receiving hospitals may be found to be in short supply and there may be capacity issues within local radiology services. Local specialists such as stroke physicians/neurologists are also in short supply and may find it difficult to cover 24/7 rotas for the assessment of acute strokes for thrombectomy. Rapid referral pathways and transport to the neuroscience centre will have to be established.

Thrombectomy for commissioners

NHS England will routinely commission MT and issued a document entitled Clinical Commissioning Policy: mechanical thrombectomy for acute ischaemic stroke on 2 March 2018.3 There are approximately 80,000 stroke admissions in England per year.3 Currently, around 12% of all stroke patients receive intravenous thrombolysis and an estimated 8000 patients per year may be eligible for thrombectomy.3 Funding and commissioning of mechanical thrombectomy will be managed through the relevant local NHS England specialised commissioning team.3

Future directions

Recent evidence suggests that in future, even more patients (including those with unknown time of onset and patients who wake up with strokes) may be eligible for MT. The use of advanced imaging (CT perfusion or MR diffusion and perfusion scans) can demonstrate salvageable brain tissue regardless of the time of onset of the stroke.32 The DAWN trial treated patients who were last known to be well 6 to 24 hours earlier and had a mismatch between the severity of the clinical deficit and the infarct volume (assessed by diffusion-weighted MRI or perfusion CT). The study found outcomes at 90 days were better with MT plus standard care than with standard care alone.33 The DEFUSE 3 trial found that MT for ischaemic stroke 6 to 16 hours after a patient was last known to be well plus standard medical therapy resulted in better functional outcomes than standard medical therapy alone among patients with proximal middle-cerebral-artery or internal-carotid-artery occlusion and a region of tissue that was ischemic but not yet infarcted (assessed by CT perfusion or MRI diffusion and perfusion scans).27 The NHS England criteria for commissioning allow for the extension of the time window to 12 hours if advanced brain imaging (perfusion or multiphase computed tomography angiography [CTA]) indicates substantial salvageable brain tissue is still present.3

Summary

Mechanical thrombectomy is a new treatment modality for a subset of acute ischaemic strokes that has been proven to be very effective (NNT approximately 3);24 however, it will be necessary to overcome some practical difficulties for the treatment to be universally implemented. An estimated 10%34 of strokes will benefit from this treatment but, as with any other stroke, high quality stroke unit care in the acute and rehabilitation phases is needed for good patient outcomes.

Dr Dipankar Dutta

Consultant Stroke Physician, Gloucestershire Royal Hospital

For further clinical detail on mechanical thrombectomy, see the November 2018 issue of our sister publication, Specialised Commissioning, where Dr Dipankar Dutta has contributed an article aimed at healthcare professionals and managers with an interest in specialised commissioning (see specialised-commissioning.co.uk).

Key points

  • Stroke remains a significant cause of mortality and ongoing disability
  • More than one-third of acute ischaemic strokes are caused by large artery occlusion
  • Mechanical thrombectomy is a breakthrough in the management of acute ischaemic stroke that is due to large artery occlusion, showing superior results in comparison to intravenous thrombolysis
  • The time window for treatment using mechanical thrombectomy is up to 6 hours or longer in selected patients
  • Mechanical thrombectomy can also be used in some patients with contraindications to intravenous thrombolysis
  • Mechanical thrombectomy has been accepted as standard treatment in stroke guidelines from NICE and is to be routinely commissioned by NHS England
  • There are significant barriers to the full implementation of round-the-clock mechanical thrombectomy but much progress is being made.

Implementation actions for STPs and ICSs

written by Dr David Jenner, GP, Cullompton, Devon

The following implementation actions are designed to support STPs and ICSs with the challenges involved with implementing new guidance at a system level. Our aim is to help you consider how to deliver improvements to healthcare within the available resources. 

  • Formulate plans for providing this life-changing intervention for certain patients
  • Convene local stroke specialist teams to consider the impact of this intervention and the service delivery challenges it poses:
    • ensure that these teams are led by NHS England as lead commissioner but include representatives from commissioners’ local acute units, specialist units, GPs’ patient representatives, and ambulance trusts
  • Scope the potential models for intervention locally with respect to your geography and available resources
  • Implement the chosen plan when resources allow and adapt the local acute stroke care pathways to accommodate this
  • Publicise the pathway widely and ensure that all first-contact healthcare professionals understand it:
    • ensure also that the public understand why they may be treated further away from home to achieve optimal outcomes.

STP=sustainability and transformation partnership; ICS=integrated care system

References

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  2. National Audit Office. Progress in improving stroke care London: The Stationery Office, 2010. Available at: www.nao.org.uk/report/department-of-health-progress-in-improving-stroke-care/
  3. NHS England Specialised Commissioning team. Clinical Commissioning Policy: mechanical thrombectomy for acute ischaemic stroke (all ages). NHS England, 2018. Available from: www.england.nhs.uk/publication/clinical-commissioning-policy-mechanical-thrombectomy-for-acute-ischaemic-stroke-all-ages/
  4. White P, Bhalla A, Dinsmore J et al. Standards for providing safe acute ischaemic stroke thrombectomy services (September 2015). Clin Radiol 2017; 72 (2): 175.e1–175.e9.
  5. Bhatia R, Hill M, Shobha N et al. Low rates of acute recanalization with intravenous recombinant tissue plasminogen activator in ischemic stroke: real-world experience and a call for action. Stroke 2010; 41 (10): 2254–2258.
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  17. Saver J, Goyal M, Bonafe A et al, for the SWIFT PRIME Investigators. Stent-retriever thrombectomy after intravenous t-PA vs. t-PA alone in stroke. N Engl J Med 2015; 372 (24): 2285–2295.
  18. Goyal M, Demchuk A, Menon B et al, for the ESCAPE Trial Investigators. Randomized assessment of rapid endovascular treatment of ischemic stroke. N Engl J Med 2015; 372 (11): 1019–1030.
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  20. Mocco J, Zaidat O, von Kummer R et al, for the THERAPY Trial Investigators. Aspiration thrombectomy after intravenous alteplase versus intravenous alteplase alone. Stroke 2016; 47 (9): 2331–2338.
  21. Muir K, Ford G, Messow C et al, on behalf of the PISTE Investigators. Endovascular therapy for acute ischaemic stroke: the Pragmatic Ischaemic Stroke Thrombectomy Evaluation (PISTE) randomised, controlled trial. J Neurol Neurosurg Psychiatry 2017; 88 (1): 38–44.
  22. Khoury N, Darsaut T, Ghostine J et al, for the EASI trial collaborators. Endovascular thrombectomy and medical therapy versus medical therapy alone in acute stroke: a randomized care trial. J Neuroradiol 2017; 44 (3): 198–202.
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  24. Campbell B, Hill M, Rubiera M et al. Safety and efficacy of solitaire stent thrombectomy. Stroke 2016; 47 (3): 798–806.
  25. Bush C, Kurimella D, Cross L et al. Endovascular treatment with stent-retriever devices for acute ischemic stroke: a meta-analysis of randomized controlled trials. PLoS One 2016; 11 (1): e0147287.
  26. Balami J, White P, McMeekin P et al. Complications of endovascular treatment for acute ischemic stroke: Prevention and management. Int J Stroke 2018, 13 (4): 348–361.
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  28. NICE. Stroke and TIA. NICE Clinical Knowledge Summary. NICE, 2017. Available at: cks.nice.org.uk/stroke-and-tia#!topicsummary
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  31. Lenthall R, McConachie N, White P et al. BSNR training guidance for mechanical thrombectomy. Clin Radiol 2017; 72 (2): 175.e11–175.e18.
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  34. McMeekin P, White P, James M et al. Estimating the number of UK stroke patients eligible for endovascular thrombectomy. Eur Stroke J 2017; 2 (4): 319–326.