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Saturday 15 December 2018
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Mechanical thrombectomy in acute ischaemic stroke

Stroke is the second single most common cause of death in the world, with 6.7 million stroke-related deaths each year.1 The burden of disease (disability, illness and premature deaths) caused by stroke is set to double worldwide by 2030.1 Stroke affects 152,000 people annually in the UK; that is 1 person every 3 minutes 27 seconds.2 Large vessel occlusion often causes severe strokes and is associated with high mortality, morbidity, poor clinical outcomes and high societal costs.3
 
The benefit of intravenous thrombolysis with recombinant tissue-type plasminogen activator for patients with severe stroke due to large artery occlusion is limited; early recanalisation is generally less than 30% for carotid, proximal middle cerebral artery or basilar artery occlusion.4 An untreated patient with a severe stroke score (NIHSS >15) would require permanent long-term rehabilitation care with an in-hospital stay of 60–90 days, which costs hospitals around £31,500 per patient.5 Patients with such severe strokes had a 1-year mortality rate of over 50% as the previous conventional treatment failed in majority of cases. Among those who survived, many (>70%) would require nursing home care.5 
 
Mechanical thrombectomy using state of the art devices has revolutionised the treatment of patients with severe disabling strokes due to large vessel occlusion with proven efficacy in re-establishing intracranial circulation and thereby showing improved patient clinical outcomes.6 A new era of acute stroke treatment began in November 2014, when nine published randomised controlled trials of mechanical thrombectomy showed better functional outcome with mechanical thrombectomy compared with best medical therapy (Table 1), leading to a revolution in the care of patients with severe disabling acute large vessel ischaemic stroke.7
 
Table 1: Effect of mechanical thrombectomy compared with best  medical therapy on good functional outcome (modified Rankin  Score ≤2 at 90 days)
 
The number needed to treat (NNT) with mechanical thrombectomy for a benefit to functional outcome is as low as 3 (range 3–7).8 This is more effective than the NNT for percutaneous coronary intervention in preventing death in acute coronary syndromes (NNT 30), and the NNT for carotid endarterectomy to prevent one stroke 
(NNT 26).8 Hence, in comparison, MT is one of the most effective treatment innovations of this decade. 
 
This treatment, which offers fresh hope that clinicians will be able to reverse the effects of a stroke in some of the most serious cases, was adopted by the Department of Health in April 2017, to be rolled out to the rest of the National Health Service (NHS) in the UK in due course.
 

Stroke diagnostic pathway and patient selection

A neurological examination is performed on all patients with suspected hyperacute stroke. National Institutes of Health Stroke Scale (NIHSS) score is performed at the time of admission by the stroke team. Patients presenting with NIHSS ≥6 and within six hours of symptom onset for anterior circulation stroke or 12 hours for posterior circulation strokes are considered for mechanical thrombectomy.  
 
As per the NCCCC guidelines,9 plain CT of the brain is performed immediately to exclude patients with contraindications to treatment, such as acute haemorrhage or significant established ischaemia. For middle cerebral artery territory symptoms, the Alberta Stroke Program Early CT Score (ASPECTS) is performed to assess the degree of established ischaemia. Patients with a lack of extensive early ischaemic change (those with ASPECTS more than 5 on plain CT) are selected.8
 
If there are no contraindications to treatment, then a CT angiogram is performed from aortic arch to the vertex. This helps to delineate the vascular anatomy and assess the patency of the intracranial arterial system, as well as the degree of collateral supply. In patients with uncertain time of symptom onset, brain perfusion imaging (CT or MRI) may be employed.8 The decision to proceed with mechanical thrombectomy is made in conjunction with a stroke physician considering the patient’s clinical condition, age and co-morbidities. 
 

Neuro-interventional pathway

Once the decision is made to proceed with mechanical thrombectomy, patients are consented and taken to interventional theatre. Intravenous tissue plasminogen activator (TPA) is given as a bridging therapy, which is then followed by intra-arterial thrombolysis and mechanical thrombectomy. MT is performed under general anaesthesia or conscious sedation. In our institution, we use a Philips Allura Xper FD20/20 biplane X-ray system for image guidance, as it enables FAST acquisition and 3D planning of the Circle of Willis.
 
Arterial access is gained by using Seldinger catheterisation of the right common femoral artery. A target vessel diagnostic angiography is performed to localise the level of occlusion.The main two basic thrombectomy techniques involve the use of suction with a pump and/or a stentriever as described below. 
  1. Suction is performed using a large bore (5F or 6F) catheter, which is engaged with the thrombus and suction is applied either directly with a syringe or a suction pump. 
  2. A stentriever is a retrievable stent, which is deployed across the thrombus and then pulled back to remove the thrombus. The most common stentrievers used are the Solitaire™ FR Revascularization Device (Covidien, ev3 Neurovascular, USA) and the Trevo Pro (Stryker Neurovascular, Kalamazoo, MI).
 
The precise mechanical thrombectomy technique is tailored for each patient based on the following factors:  
  1. Vascular tortuosity of the aortic arch, internal carotid artery (ICA) or vertebrobasilar artery (VBA) 
  2. The level of occlusion – This may occur at the internal carotid artery (ICA), vertebral artery (VB), basilar artery (BA), middle cerebral artery (MCA, 1st segment M1) or posterior cerebral artery (PCA, 1st segment P1)
 
Length of the thrombus – This can be measured from the CT angiogram. 
 
Using these criteria, a number of techniques of performing mechanical thrombectomy are described8 and summarised in Figure 1. 
 
Figure 1: Summary of mechanical thrombectomy techniques
 

Basic stentriever technique

Figure 2 shows the basic method for this technique. 
 
Figure 2: Basic stentriever technique.
Figure 2 Basic stentriever technique. A, B) AP and lateral views of pre-procedural catheter angiogram showing MCA occlusion in a patient with straight cervical ICA; C) Microcatheter advanced across the thrombus; D) Stentriever positioned across the thrombus; E,F) AP and lateral post-procedure catheter angiogram showing complete revascularisation. 
 
A 6F or 8F guide catheter is introduced to the arch of aorta under fluoroscopic guidance and then placed into the target vessel ICA or VBA.10
 
A micro catheter is then negotiated across the thrombus by tracking over a guidewire. The stentriever device is then passed through the microcatheter so that it is positioned across the thrombus. Next, the device is unsheathed and concurrently deployed by withdrawal of the microcatheter, straddling the thrombus. After placing the device within the thrombus for 3–5 minutes, the device is then pulled back in its expanded state along with continuous aspiration from a 50ml syringe via the guide catheter. 
 
Up to five passes using this technique may be performed if initially unsuccessful.11 An improved final recanalisation success rate using Thrombolysis in Cerebral infarction (TICI) score of 2b–3 is often achieved using this combined stentriever–aspiration mechanical thrombectomy.12
 

Use of anaesthesia during the procedure 

The use of general versus local anaesthesia or conscious sedation currently varies.. General anaesthesia reduces subject distress and movement, and it can make the technical aspects easier; by contrast, conscious sedation allows continuous neurological monitoring for complications, and it avoids any potential hazard of general anaesthetic agents. Two studies presented at the 3rd European Stroke Organisation Conference (ESOC) in 2017 (GOLIATH and ANSTROKE) both suggested that general anaesthesia and conscious sedation are equally safe.7 Thus, either approach currently seems reasonable and the decision can be made on the level of local anaesthetic expertise available and the clinical stability of the patient, which may point to direction of either of these approaches.
 

Procedure limitations and potential complications

Despite their superiority in improving clinical outcomes in patients with acute ischaemic strokes, stent retrievers are not without complications. Although the stent retriever devices are generally safe,13 complications of endovascular procedures can result from direct device-related vascular injury, vascular access and the use of radiological contrast media. The most common complications include the vessel perforation,14–16 which occurred in 1.6% patients in the 5% positive endovascular trials (range 0.9%–4.9%); symptomatic intracranial haemorrhage (3.6%–9.3%); subarachnoid haemorrhage (0.6%–4.9%); arterial dissection (0.6%–3.9%); emboli to new territories (1.0%–8.6% in randomised controlled trials); vasospasm; and vascular access site complications (including dissection, pseudoaneurysm, retroperitoneal haematoma and infection).
 
Another side effect of using stents in the treatment of acute ischaemic stroke is acute in-stent thrombosis in cases where the stent is permanently left in place following successful recanalisation. In that case, a half-systemic loading dose of a factor IIb/IIIa inhibitor, such as eptifibatide or abciximab, may be delivered intra-arterially via the guide catheter.17 Techniques requiring a larger 8F system have slightly increased risk of arterial injury especially in elderly patients with atherosclerotic vessels.18
 
The overall procedural complication rate from recent randomised controlled trials is in the range of 15%, but it must be emphasised that many do not adversely affect clinical outcome. Stent retriever detachment19–21 is an uncommon complication (about 2%–3% with first-generation Solitaire FR device, but anecdotally much lower with latest versions). The key strategy to minimise complications is for thrombectomy to be only performed in high-volume centres by trained physicians competent in intracranial endovascular procedures. 
 
In the event of a complication, there should be immediate availability of neurocritical care and neurosurgical support, which are essential and prove life-saving.
 

Social benefit and cost effectiveness

The only data on cost effectiveness of mechanical thrombectomy were published by the National Institute for Health and Care Excellence (NICE) in March 2016.5 The data showed that patients undergoing mechanical thrombectomy had good clinical outcomes, with 50% of patients alive and independent with no significant disability (mRS<2). It also showed mortality rates of 17 compared with 50% 1-year mortality previously for such a subset of patients.5 The median hospital stay for patients undergoing MT in the study was 14 days, less than a sixth of the previous figure of 60–90 days. More than 90% of patients were discharged home, compared with the previous situation in which >70% would go to a nursing home because of significant impairment, and 23% of patients undergoing MT were discharged home within one week.6
 
Patients with severe strokes have a prolonged hospital stay of 60–90 days, which costs £31,500 per patient.5 The community cost for disabled stroke patient ranges between £28,600/year to £68,000/year.5 NICE data showed that offering the procedure could achieve savings of £2.4 million a year as a result of reduced time in hospital and savings from ongoing social care costs.5 An estimated £440 million annual savings could be generated to the NHS and social care once full national implementation of mechanical thrombectomy takes place.5
 
Following the adoption of this procedure by the Department of Health, it has now been fully-funded through specialised commissioning by NHS England and the agreed funding level is £12,500 per patient, which includes the hyperacute costs of the intervention. This will help all the UK Tertiary Neurosciences centres to build an infrastructure to develop and safely deliver this service. This intervention has the potential to save millions of pounds to the NHS if fully implemented on a large UK scale.
 

Further developments and new guidelines

In the new American Acute Ischemic Stroke Guidelines, the time window for mechanical thrombectomy has been increased to 24 hours if patients meet DAWN or DEFUSE-3 criteria, where advanced imaging plays a major role.22
 
The DAWN trial used clinical imaging mismatch (a combination of NIHSS score and imaging findings on CTP or DW-MRI) as eligibility criteria to select patients with large anterior circulation vessel occlusion for treatment with mechanical thrombectomy between 6 and 24 hours from last known normal.23 This trial demonstrated an overall benefit in function outcome at 90 days in the treatment group (mRS score 0–2, 49% versus 13%; adjusted difference, 33%; 95% CI 21–44; posterior probability of superiority >0.999).22,23  The DEFUSE 3 trial used perfusion-core mismatch and maximum core size as imaging criteria to select patients with large anterior circulation occlusion 6–16 hours from last seen well for MT.24 This trial showed a benefit in functional outcome at 90 days in the treated group (mRS score 0–2, 44.6% versus 16.7%; RR, 2.67; 95% CI 1.60–4.48; p<0.0001).22,24
 

Conclusions

Mechanical thrombectomy with modern stentriever devices achieves superior clinical outcome in acute stroke patients compared with medical therapy alone. This has revolutionised acute stroke care and is considered as one of the top innovations of the decade. However, its development is still in the early phases and for full-fledged implementation, there is a requirement of further investment to help develop care pathways, workforce, technological investment for diagnostic and therapeutic execution and improved infrastructure for patient transfer services including ambulance services and in-hospital pathways.
 

References

1 World Health Organization. The top 10 causes of death. www.who.int/mediacentre/factsheets/fs310/en/ (accessed April 2018). 
2 Feigin VL et al. Global and regional burden of stroke during 1990–2010: findings from the Global Burden of Disease Study 2010. Lancet 2013;383(9913):245–54.
3 Townsend N et al. Coronary heart disease statistics; 2012 edition. London: British Heart Foundation:57.
4 Bhatia R 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;41:2254–8.
5 National Institute for Health and Clinical Excellence. Mechanical thrombectomy for large vessel occlusion stroke: improving clinical outcomes and reducing cost. Quality and productivity case study. March 2016. www.nice.org.uk/savingsandproductivityandlocalpracticeresource?id=2599 (accessed April 2018).
6 Goyal M et al. Endovascular thrombectomy after large-vessel ischaemic stroke: a meta-analysis of individual patient data from five randomised trials. www.mrclean-trial.org/docs/Goyal_ HERMESmetaanalyse_2016 Lancet.pdf (accessed April 2018).
7 Evans M et al. Revolution in acute ischaemic stroke care: a practical guide to mechanical thrombectomy. Pract Neurol 2017;17(4):252–65.
8 Nayak S et al. Mechanical thrombectomy in acute ischaemic stroke: a review of the different techniques. Clin Radiol 2018;73(5):428–38. 
9 Stroke: national clinical guideline for diagnosis and initial management of acute stroke and transient ischaemic attack (TIA). London: Royal College of Physicians; 2008.
10 Dorn F et al. Endovascular treatment of acute intracerebral artery occlusions with the solitaire stent: single-centre experience with 108 recanalization procedures. Cerebrovasc Dis 2012;34(1):70–7.
11 Zaidat OO et al. Recommendations on angiographic revascularization grading standards for acute ischemic stroke: a consensus statement. Stroke 2013;44(9):2650–63.
12 Eesa M et al. Manual aspiration thrombectomy through balloon-tipped guide catheter for rapid clot burden reduction in endovascular therapy for ICA L/T occlusion. Neuroradiology 2012;54(11):1261–5.
13 Campbell BC et al Safety and efficacy of Solitaire stent thrombectomy: individual patient data meta-analysis of randomized trials. Stroke 2016;47:798–806. 
14 Gascou G et al. Stent retrievers in acute ischemic stroke: complications and failures during the perioperative period AJNR Am J Neuroradiol 2014;35:734–40. 
15 Leishangthem L, Satti SR. Vessel perforation during withdrawal of Trevo ProVue stent retriever during mechanical thrombectomy for acute ischemic stroke J Neurosurg 2014;121:995–8. 
16 Mokin M et al. Vessel perforation during stent retriever thrombectomy for acute ischemic stroke: technical details and clinical outcomes. J Neurointerv Surg 2016:neurintsurg-2016-012707. 
17 Schneider DJ. Anti-platelet therapy: glycoprotein IIb-IIIa antagonists. Br J Clin Pharmacol 2011;72(4):672–82. 
18 Arai D et al. Histological examination of vascular damage caused by stent retriever thrombectomy devices. J Neurointerv Surg 2016;8(10):992–5. 
19 Ahmad N et al. Mechanical thrombectomy for ischaemic stroke: the first UK case series. PLoS One 2013;8(12):e82218.
20 Akpinar S, Yilmaz G. Spontaneous Solitaire™ AB thrombectomy stent detachment during stroke treatment. Cardiovasc Intervent Radiol 2015;38:475–8. 
21 Kim ST et al. Unexpected detachment of Solitaire stents during mechanical thrombectomy. J Korean Neurosurg Soc 2014;56:463–8.
22 Powers WJ et al. Guidelines for the early management of patients with acute ischemic stroke. A guideline for healthcare professionals 2018. http://stroke.ahajournals.org/content/49/3/e46 (accessed April 2018).
23 Nogueira RG et al. Thrombectomy 6 to 24 hours after stroke with a mismatch between deficit and infarct. N Engl J Med 2018;378(1):11–21. 
24 Albers GW et al. Thrombectomy for stroke at 6 to 16 hours with selection by perfusion imaging. N Engl J Med 2018;378(8):708–18.

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