Rationale and impact
- Initial management of suspected and confirmed transient ischaemic attack (aspirin)
- Initial management of suspected and confirmed transient ischaemic attack
- Imaging for people who have had a suspected TIA or acute non-disabling stroke
- Thrombectomy for people with acute ischaemic stroke
- Blood pressure control for people with acute intracerebral haemorrhage
- Optimal positioning for people with acute stroke
- Early mobilisation for people with acute stroke
- Decompressive hemicraniectomy for people with acute stroke
These sections briefly explain why the committee made the recommendations and how they might affect practice. They link to details of the evidence and a full description of the committee's discussion.
There was some evidence for a benefit of aspirin in the early management of confirmed transient ischaemic attack (TIA) or minor stroke in reducing the risk of stroke or recurrent stroke in secondary care in stroke services units. This is not directly applicable to the area of review, which was about TIA at first contact with a healthcare professional. However, in the committee's experience, the earlier that aspirin can be administered the better this will also be for patient outcomes in this group. The risk of haemorrhage in this group, and of other risks associated with administering aspirin (aspirin allergy or gastrointestinal bleed), is low. The recommendation was based largely on the knowledge and experience of the committee supported by the indirect evidence.
The recommendation represents a change from current practice. However, because of the low unit cost of aspirin, the committee did not expect the recommendation to result in a significant resource impact. General practices will need to ensure they have adequate supplies of aspirin to enable immediate administration.
Full details of the evidence and the committee's discussion are in evidence review A: aspirin.
Evidence showed that risk prediction scores (ABCD2 and ABCD3) used in isolation are poor at discriminating low and high risk of stroke after TIA. Adding imaging of the brain and carotid arteries to the risk scores (as is done in the ABCD2‑I and ABCD3‑I tools) modestly improves discrimination. However, appropriate imaging (including MRI) is not available in general practice or for paramedics, 2 of the key situations when these tools would be used. Arranging specialist assessment less urgently for some people based on a tool with poor discriminative ability for stroke risk has the potential for harm. Therefore, the committee agreed that risk scores should not be used.
The committee agreed, based on their clinical experience and the limited predictive performance of risk scores, that all cases of suspected TIA should be considered as potentially high risk for stroke. Also, because there is no reliable diagnostic test for TIA (the risk stratification tools are not diagnostic tests), it is important to urgently confirm or refute the diagnosis of a suspected TIA with specialist opinion. This is particularly so because in practice, a significant proportion of suspected TIA (30% to 50%) will have an alternative diagnosis (that is, TIA-mimic). Therefore, it was agreed that everyone who has had a suspected TIA should have specialist assessment and investigation within 24 hours of the onset of symptoms. The committee noted the results of an original cost–utility analysis, which was undertaken for this review question in the 2008 version of the stroke guideline (CG68). The analysis concluded that 'immediate assessment' had both better health outcomes and lower costs than 'assessment within a week' for the entire population of suspected TIA, without the use of a risk stratification tool.
The committee acknowledged that having a TIA (or suspected TIA) is a worrying time and most people would prefer to be assessed as soon as possible. Urgent specialist assessment should ensure that people at high risk of stroke are identified early. This would allow preventative treatment to begin, which should be introduced as soon as the diagnosis of TIA is confirmed.
The recommendations reflect current best practice of expert assessment in a TIA clinic within 24 hours, irrespective of risk stratification using clinical scoring systems. Although everyone with a suspected TIA should be seen within 24 hours, provision of daily TIA clinics is not universal. Therefore, some areas will need to set up daily TIA clinics to provide this best practice service.
The recommendations should not influence the absolute number of people who need to be subsequently assessed in a TIA clinic, but will result in all suspected TIAs being assessed with an equal degree of urgency. There are likely to be implementation challenges for some areas in providing an adequately responsive 7‑days-a-week TIA clinic (or a suitable alternative 7-day service) where they currently do not exist. However, services are already being encouraged to implement TIA clinics 7 days a week. The committee acknowledged that setting up responsive (7 days a week) services in trusts that do not currently offer daily clinics could require significant additional resource and this may result in a substantial resource impact for the NHS in England. However, preventing stroke is likely to result in cost savings later on.
The recommendation on offering measures for secondary prevention reflects current practice so no change is expected.
Full details of the evidence and the committee's discussion are in evidence review B: TIA prediction rules.
No evidence was identified from test-and-treat trials (which the committee considered would have been the most useful form of evidence to inform decision making). In these studies, different imaging strategies are performed on randomised groups followed by management on the basis of the results, to compare patient outcomes after different imaging strategies. Therefore, the committee used their knowledge and experience to conclude that clinical assessment is the best form of diagnosis at this point. The committee agreed that CT is most useful when there is a clinical suspicion of an alternative diagnosis that CT could detect. It should not be routinely performed for everyone with a suspected TIA because it rarely confirms a diagnosis in these patients.
Routine CT imaging is common in current practice and the committee agreed that this could waste resources, extend the length of stay in the emergency department, and expose people to unnecessary radiation.
The committee discussed the possible risks of not offering CT brain imaging to everyone with a suspected TIA. They agreed that, in the absence of clinical 'red flag' indicators (for example, headache, anticoagulation, head injury, repetitive stereotyped events), it is rare for a CT scan to reveal an alternative diagnosis needing a different referral pathway. Therefore, the number of referrals to TIA clinics should not increase greatly.
In a TIA clinic, not all people will need an MRI. Therefore, clinical assessment by a specialist in a TIA clinic is important for identifying people who may need MRI to determine the vascular territory of ischaemia (the region of the brain with loss of blood flow, supplied by either the anterior or posterior circulation). For example, this could be before a decision is made to refer for a carotid endarterectomy, or to detect alternative pathologies such as tumours, demyelinating disorders or convexity subarachnoid haemorrhage. There was uncertainty about whether urgent, routine MRI screening improves the outcomes for people with suspected TIA, and so the committee made a research recommendation in this area.
Not routinely offering CT brain imaging will be a change in practice for some providers (especially in the emergency department), whereas MRI use in the TIA clinic aligns broadly with current practice.
The committee was uncertain whether these recommendations will be cost saving overall. It will be a trade-off between a reduction in CT requests against a potential increase in MRI requests. The committee also highlighted that any increase in MRI requests may be small because the decision to perform an MRI will not generally be affected by the results of a previous CT scan.
The committee recognised that if there was an increase in MRI requests, this could be a challenge because access to high-quality MRI scanners is limited in some trusts. In addition, there are limits on the number of MRI slots per day, so there may be a need for dedicated MRI slots for people with suspected TIA.
Full details of the evidence and the committee's discussion are in evidence review C: TIA imaging.
Overall, the evidence across time-frames showed that thrombectomy, with or without thrombolysis, improved functional outcome as measured by the modified Rankin scale (mRS) in people last known to be well up to 24 hours previously, compared with usual care. There was also a potential benefit for improved quality of life. However, there was no clinical difference in mortality and there were low rates of symptomatic intracerebral haemorrhage. The committee noted there had been some procedural complications associated with thrombectomy, but agreed that these were outweighed by the benefits of improvement in functional outcome.
The committee looked at the results of 2 published cost–utility analyses with a UK NHS perspective. The first estimated that thrombectomy alongside intravenous thrombolysis (when appropriate) is cost effective compared with intravenous thrombolysis alone, when performed within 6 hours of stroke onset (that is, from when a person was last known to be well). The second demonstrated the cost effectiveness of thrombectomy therapy and best medical therapy compared with best medical therapy alone, when performed 6 to 24 hours after stroke onset. Therefore, the committee agreed to recommend thrombectomy up to 24 hours after stroke onset, together with intravenous thrombolysis if within the licensed time window, for people with appropriate clinical and radiological characteristics. Few people presenting between 6 and 24 hours after stroke onset received thrombolysis because this is outside the licensed time window. Therefore, the recommendation for those presenting beyond 6 hours is for thrombectomy alone.
The evidence for thrombectomy within 6 hours of symptom onset was from populations selected using computed tomographic angiography (CTA) or magnetic resonance angiography (MRA) to identify proximal anterior circulation occlusions. For thrombectomy undertaken between 6 and 24 hours after stroke onset, the evidence was based on more highly selected populations using CT perfusion, MRI diffusion and MRI perfusion imaging, in addition to identifying a proximal anterior circulation arterial occlusion. Because the effectiveness of thrombectomy is likely to be lower in a less selected population, the committee recommended that, in line with the evidence, imaging such as CT perfusion or diffusion-weighted MRI sequences is performed if presentation is 6 to 24 hours after stroke onset in people being considered for thrombectomy. This would ensure that there is vulnerable but salvageable brain tissue to be targeted for thrombectomy. Although benefit is still seen up to 24 hours after stroke, time is still critical. Therefore, the committee agreed that thrombectomy should be performed as soon as possible.
To help determine what clinical characteristics make this intervention suitable, it is important to consider the National Institutes of Health Stroke Scale (NIHSS) score and the person's overall functional capacity before the stroke. The committee agreed that it was not possible on the basis of the evidence reviewed to specify strict threshold criteria for eligibility based on pre-stroke functional status, clinical severity of stroke or the extent of established infarction on initial brain imaging. This is because there was variation in the trial entry criteria used in the studies and the committee agreed that these factors should be considered as part of the clinical judgement on an individual basis. However, because it was important to make a recommendation that can be implemented in practice, mRS and NIHSS eligibility thresholds were included to be consistent with the NHS England clinical commissioning policy on mechanical thrombectomy for acute ischaemic stroke.
No clinical- or cost-effectiveness evidence was identified for the population with posterior circulation stroke. The committee discussed that prognosis is usually very poor in basilar artery occlusion, with around an 80% mortality. As few as 2 to 5% of people with basilar artery occlusion make a full neurological recovery in the absence of interventions to achieve recanalisation or reperfusion. The committee agreed that the prevalent current practice is to consider intravenous thrombolysis and mechanical thrombectomy. Good outcomes can be achieved even up to 24 hours after stroke onset, which is important because diagnosis can be delayed in this population by a non-focal presentation, a reduced conscious level, or both.
The main risk of thrombectomy and thrombolysis in this population is intervening when there is established disabling ischaemic brain injury. For example, if a person with basilar artery occlusion has irreversible bilateral damage to the pons, they may be left with locked-in-syndrome with complete face and body paralysis but clear consciousness, even if the basilar artery is opened. The committee agreed that it is standard practice to perform brain imaging and look for established tissue damage in the brain regions affected by the arterial occlusion, particularly in the brainstem, before intervening. This reduces the number of people surviving with severe neurological disability. Appropriate CT perfusion imaging or diffusion-weighted MRI sequences should be performed to demonstrate that there is salvageable brain tissue and to seek evidence of established injury to functionally critical areas of the posterior circulation.
The outlook for this population without intervention is poor, but good outcomes can be achieved with intervention and there is supportive evidence from treating anterior stroke. Therefore, the committee agreed that thrombectomy, and thrombolysis within its licensed indications, should be considered for people with posterior circulation proximal occlusions and without evidence of irreversible infarction who were last known well up to 24 hours previously. This should be done as soon as possible after presentation because better outcomes are likely with earlier intervention.
The committee noted that in current practice, around 10% of people presenting with all strokes in the UK are eligible for endovascular therapy. More people are likely to be offered endovascular therapy as a result of these recommendations. The recommendation on thrombectomy together with thrombolysis within 6 hours of symptom onset is aligned with current best practice and the NHS England clinical commissioning policy on mechanical thrombectomy for acute ischaemic stroke. The recommendation for thrombectomy between 6 and 24 hours requires a change from current practice by most providers. Currently, the NHS England clinical commissioning policy states that mechanical thrombectomy will be commissioned when substantial salvageable brain tissue is identified up to 12 hours. However, this extension of the eligibility period up to 24 hours was supported by clinical- and cost-effectiveness evidence as discussed above. The recommendation to consider endovascular therapy for posterior circulation stroke reflects current best practice.
Overall, the new recommendations are likely to have a substantial resource impact on the NHS. Thrombectomy is already performed in most neuroscience centres, but the recommendations will mean 24-hour access to appropriate staffing and imaging.
The committee discussed the possibility that the new recommendations could initially result in a large increase in referrals to centres that already have thrombectomy services. It also noted that there are likely to be additional costs incurred in transferring people to these centres. This will have implications for the spoke site for arranging transfers, for the ambulance service and at the hub site, where more people will be received. There may need to be networked arrangements for spoke sites around a thrombectomy 'hub' with fast image transfer, referral, eligibility assessment and responsive repatriation systems.
The positive implications for other aspects of stroke care help to address the balance in demand for resources. For example, it is expected that there will be a decrease in demand for decompressive hemicraniectomies and inpatient rehabilitation. There may also be a reduction in the need for long-term social care.
Full details of the evidence and the committee's discussion are in evidence review D: thrombectomy.
Good quality evidence from a large number of trial participants showed no clear harm associated with rapidly lowering blood pressure for the groups covered by the recommendation using a systolic blood pressure target of 130 to 140 mmHg within 1 hour of starting treatment compared with standard blood pressure lowering. Specifically, no clinically relevant increase in the risk of neurological deterioration caused by reduced blood flow to the brain or renal failure caused by rapidly lowering systolic blood pressure was found. The intervention achieved a good functional outcome (defined as an mRS score of 0 to 2), and the potential to improve quality of life, which was agreed to be clinically meaningful.
The committee noted that 1 trial used an even more aggressive blood pressure lowering strategy, with treatment started within 4.5 hours of symptom onset and a systolic blood pressure target of 110 to 139 mmHg. However, this was associated with an increased incidence of renal failure compared with standard treatment. Therefore, to avoid this risk of harm, the lower limit for the systolic blood pressure target has been defined as 130 mmHg. The mortality rate without intervention is thought to be around 40% at 1 month, and up to 60% of people who do survive have moderate or severe disability. Therefore, any intervention to reduce this is important. It is also important to standardise care in this area where much inconsistency is known to exist.
There was little or no evidence on people presenting beyond 6 hours or those with a systolic blood pressure over 220 mmHg. However, the committee agreed that guidance is needed on treating hypertension in these groups and that it is logical to extrapolate from the available data to these groups. Therefore, they used their knowledge and experience to make a recommendation to consider rapid systolic blood pressure reduction in these groups when clinically appropriate.
The committee made a recommendation to not offer rapid blood pressure lowering to specific groups that were excluded from the key clinical trial. This is because there is no evidence of whether this would be safe or beneficial.
The recommendations reflect current best practice but might require a change in some settings because practice is currently variable. Although there is variation in current practice, this protocol is already being widely implemented in most trusts. Therefore, it is not expected to result in a substantial resource impact to the NHS in England.
Full details of the evidence and the committee's discussion are in evidence review E: blood pressure (maintenance of homeostasis).
The evidence did not indicate any difference in outcomes between lying flat or with the head elevated. No cost-effectiveness evidence was identified and no cost difference between the 2 strategies is expected. Therefore, the committee used their knowledge and experience to recommend positioning people according to their preferences and individual requirements.
Optimal positioning is an important part of early acute stroke management and rehabilitation. In current practice, people are assessed in bed and optimal head positioning is determined based on clinical presentation, medical needs and patient comfort. The recommendation therefore reflects current practice in most hospitals and so the committee agreed that there should be little or no change.
Full details of the evidence and the committee's discussion are in evidence review G: head positioning.
Regarding the recommendation to mobilise people after having a stroke when their clinical condition permits, there was no clear evidence of benefit or harm for early mobilisation within the first 48 hours after symptom onset compared with standard care. Therefore, the committee made a recommendation based on their knowledge and experience. The committee agreed that early mobilisation may be appropriate in some cases where people need minimal assistance to mobilise, such as in those who have suffered a mild stroke, or are experiencing language and/or upper limb dysfunction alone.
Regarding the recommendation not to offer high-intensity mobilisation within the first 24 hours of symptom onset, a published within-trial cost-effectiveness analysis from the Australian hospital perspective was identified. However, the treatment effect for the health outcome mRS 0 to 2 used in the study differed from the treatment effect calculated in the clinical review. Because the cost-effectiveness evidence was incompatible with the results of the clinical review, the committee chose to make a recommendation based on the clinical evidence for mortality. The evidence suggested clinical harm associated with high-intensity mobilisation within the first 24 hours after acute stroke. However, based on their clinical experience they discussed that this harm was most relevant to those who need help to sit out of bed, stand or walk. Therefore, they limited the recommendation to this group because they did not want to prevent appropriate early mobilisation in people who are independently mobile after having a stroke.
The committee was confident that making these recommendations would not have a resource impact, because there was no indication that mobilising later and with a lower intensity leads to a longer length of stay. The committee noted that people will still be assessed and mobilised and there are unlikely to be differences in staff costs. In current practice, mobilisation strategies differ according to stroke severity and the clinical condition of the person with stroke. The strategy may also be impacted by the availability of different types of specialist seating. The recommendations may change current practice in stroke units where there is an 'as soon as possible' focus on mobilisation. They will encourage healthcare professionals to consider the intensity of very early mobilisation and advice on intensity of activities to people discharged from hospital early after a stroke.
Full details of the evidence and the committee's discussion are in evidence review F: very early mobilisation.
The evidence showed that surgery improved mortality rates and, to a lesser extent, functional outcomes as measured by the mRS. The benefit on mortality was seen in all age groups considered, although the benefit for functional outcome was smaller in people aged over 60 years than in people under 60 years. Based on this, and to ensure that people over 60 have similar opportunities for the surgery as younger people, the committee removed the previous age cut-off for considering surgery. The committee also acknowledged that although surgery results in more people surviving and better functional outcome than without surgery, many still have overall poor functional outcome and their quality of life may be low. The acceptability of this trade-off was agreed to be a very individual judgement. Some people may choose not to have surgery if there is a risk of severe disability, whereas others may wish to go ahead based on mortality benefit alone. Therefore, the committee highlighted the need for careful discussion about risks and benefits between clinicians and family members or carers. They noted that patients would not be able to be involved at the time because of the severity of the stroke, so the family or carers would be responsible for making the decision. In deciding whether to opt for surgery, considerations should include pre-stroke functional status, because surgery would not be appropriate for people with severe disability before stroke.
The committee noted that although some of the trials included people who had surgery as long as 96 hours after symptom onset, the benefits in terms of reduced mortality and improved functional outcome were largely driven by studies that only allowed surgery up to a maximum of 48 hours after onset. Therefore, it agreed to retain the reference to surgery being performed within 48 hours of onset from the original recommendations. The committee also reviewed the criteria used to determine eligibility for hemicraniectomy from NICE's stroke guideline published in 2008. It was agreed that these were still appropriate and reflect the populations included in the studies used to inform the new recommendations.
The committee agreed that although the cost effectiveness of decompressive hemicraniectomy remains uncertain, it should be considered for some people because of the clear mortality benefit and the improved functional outcomes. Shared decision making between physicians, surgeons, families and carers is important given the high likelihood of residual moderate or severe disability after surgery.
In current practice, around 5% of people on the stroke unit are referred for decompressive hemicraniectomy. Decompressive hemicraniectomy is currently considered for those aged under 60.
This recommendation will require a change from current practice by all providers. The guidance will also require healthcare professionals to take into account people's pre-stroke functional status and to have a discussion about the risks and benefits.
The committee believed that including people over 60 years would not necessarily lead to significantly more people undergoing surgery because informed discussion of the outcomes might reduce its uptake in this population. In addition, increasing the population eligible for endovascular therapy and its provision is likely to decrease the population referred for decompressive hemicraniectomy. The committee therefore did not anticipate a substantial resource impact to result from this recommendation.
Full details of the evidence and the committee's discussion are in evidence review H: surgery (decompressive hemicraniectomy).