Sign 108
Sign 108
Sign 108
108
December 2008
High quality meta-analyses, systematic reviews of RCTs, or RCTs with a very low risk of bias
Well conducted meta-analyses, systematic reviews, or RCTs with a low risk of bias
1 -
Expert opinion
GRADES OF RECOMMENDATION
Note: The grade of recommendation relates to the strength of the evidence on which the
recommendation is based. It does not reflect the clinical importance of the recommendation.
A At least one meta-analysis, systematic review, or RCT rated as 1++,
and directly applicable to the target population; or
A body of evidence consisting principally of studies rated as 1+,
directly applicable to the target population, and demonstrating overall consistency of results
B
A body of evidence including studies rated as 2++,
directly applicable to the target population, and demonstrating overall consistency of results; or
C
A body of evidence including studies rated as 2+,
directly applicable to the target population and demonstrating overall consistency of results; or
Evidence level 3 or 4; or
December 2008
Management of patients with stroke or TIA: assessment, investigation, immediate management and secondary prevention
CONTENTS
Contents
1
Introduction........................................................................................................................ 1
1.1
1.2
1.3
Definitions........................................................................................................................... 2
1.4
Statement of intent............................................................................................................... 3
2 Key recommendations......................................................................................................... 4
2.1
2.2
In-hospital care..................................................................................................................... 4
2.3
2.4
2.5
2.6
Carotid intervention............................................................................................................. 5
2.7
Provision of information....................................................................................................... 5
3.1
Systems of care..................................................................................................................... 6
3.2
Pre-hospital.......................................................................................................................... 7
3.3
In-hospital............................................................................................................................ 7
4.1
Clinical assessment.............................................................................................................. 10
4.2
4.3
Carotid evaluation................................................................................................................ 12
4.4
Cardiac imaging................................................................................................................... 14
4.5
Diagnostic tests.................................................................................................................... 15
5.1
Thrombolysis....................................................................................................................... 16
5.2
Antiplatelet agents................................................................................................................ 17
5.3
Anticoagulants..................................................................................................................... 18
5.4
Neuroprotectants.................................................................................................................. 20
5.5
5.6
Decompressive surgery........................................................................................................ 21
5.7
Mechanical reperfusion........................................................................................................ 22
5.8
6.1
Haematoma evacuation........................................................................................................ 24
6.2
Thrombolysis....................................................................................................................... 24
6.3
Haemostatic therapies.......................................................................................................... 25
6.4
7.2
Physiological monitoring...................................................................................................... 28
8.2
Physiological intervention.................................................................................................... 28
Management
ofpain
patients
with stroke
or cancer
TIA: assessment, investigation, immediate management and secondary prevention
Control of
in adults
with
Antiplatelet agents................................................................................................................ 34
9.2
Statins.................................................................................................................................. 35
9.3
Anticoagulants..................................................................................................................... 36
9.4
Antihypertensives................................................................................................................. 37
9.5
9.6
Carotid endarterectomy........................................................................................................ 38
9.7
10.2
Antiplatelet agents................................................................................................................ 40
10.3
Anticoagulants..................................................................................................................... 40
10.4
Statins.................................................................................................................................. 41
11 Carotid intervention............................................................................................................ 42
11.1
Carotid endarterectomy........................................................................................................ 42
11.2
11.3
12.2
12.3
12.4
12.5
Vitamin supplements............................................................................................................ 48
12.6
Weight reduction................................................................................................................. 48
12.7
Smoking............................................................................................................................... 48
12.8
Alcohol................................................................................................................................ 48
12.9
Exercise................................................................................................................................ 49
13 Provision of information...................................................................................................... 50
13.1
13.2
14
14.1
14.2
14.3
Additional advice to NHSScotland from NHS Quality Improvement Scotland and the
Scottish Medicines Consortium............................................................................................ 56
15
15.1
15.2
15.3
Introduction......................................................................................................................... 60
16.2
16.3
Abbreviations....................................................................................................................................... 63
Annexes ............................................................................................................................................ 66
References........................................................................................................................................... 94
1 INTRODUCTION
Introduction
overall objectives
This guideline replaces SIGN 13 Management of patients with stroke I: Assessment, investigation,
immediate management and secondary prevention and SIGN 14 Management of patients with
stroke II: Management of carotid stenosis and carotid endarterectomy, which were published
in 1997.4,5
This guideline takes account of advances in both stroke treatment and imaging. The guideline
uses an updated evidence base to support recommendations for all aspects of acute stroke care
including the management of carotid stenosis.
The guideline complements SIGN 78 Management of patients with stroke: Identification and
management of dysphagia and SIGN 64 Management of patients with stroke: Rehabilitation,
prevention and management of complications, and discharge planning.6,7 As stroke shares risk
factors with cardiovascular disease, primary prevention of stroke has been covered in SIGN
97 Risk estimation and the prevention of cardiovascular disease8 and is not discussed in this
guideline.
The guideline follows the patient pathway from the onset of a suspected stroke and covers
management of suspected stroke by non-stroke specialist practitioners, and clinical and
radiological assessment. Treatment, monitoring and prevention of recurrent stroke in patients
with ischaemic stroke, transient ischaemic attack (TIA), primary intracerebral haemorrhage
(PICH) and asymptomatic carotid disease are also covered. There is also a section addressing the
information and support needs of patients and carers. Management of patients with subarachnoid
haemorrhage has not been addressed.
The guideline development group has based the recommendations in this guideline on answers
to a series of key questions (see Annex 1).
Management of patients with stroke or TIA: assessment, investigation, immediate management and secondary prevention
1.3
definitions
The definitions of some terms vary from one study to another and these outlines are not
rigid.
Stroke
Minor stroke
Disabling stroke
Cryptogenic stroke
1 INTRODUCTION
Patient version
A patient version of this guideline has been developed in collaboration with Chest, Heart &
Stroke Scotland and is available from the SIGN website, www.sign.ac.uk.
1.4.2
Management of patients with stroke or TIA: assessment, investigation, immediate management and secondary prevention
2 Key recommendations
The following recommendations were highlighted by the guideline development group as being
clinically very important. They are the key clinical recommendations that should be prioritised
for implementation. The clinical importance of these recommendations is not dependent on
the strength of the supporting evidence.
2.1
2.3
All patients with suspected stroke should have brain imaging immediately on
presentation.
All patients with non-disabling acute stroke syndrome/TIA in the carotid territory who
are potential candidates for carotid surgery should have carotid imaging.
2.4
2.4.1
Thrombolysis
A
2.4.2
Decompressive surgery
A
Patients admitted with stroke within four and a half hours of definite onset of symptoms,
who are considered suitable, should be treated with 0.9 mg/kg (up to maximum 90 mg)
intravenous rt-PA.
For individuals aged up to 60 years who suffer an acute MCA territory ischaemic stroke
complicated by massive cerebral oedema, surgical decompression by hemicraniectomy
should be offered within 48 hours of stroke onset.
2 KEY RECOMMENDATIONS
Low-dose aspirin (75 mg daily) and dipyridamole (200 mg modified release twice daily)
should be prescribed after ischaemic stroke or TIA for secondary prevention of vascular
events.
2.5.2 statins
A
A statin should be prescribed to patients who have had an ischaemic stroke, irrespective
of cholesterol level.
Statin therapy after haemorrhagic stroke is not routinely recommended unless the risk
of further vascular events outweighs the risk of further haemorrhage.
All patients with carotid artery territory stroke (without severe disability, mRS2)
or transient ischaemic attack should be considered for carotid endarterectomy as soon
as possible after the index event.
Carotid endarterectomy (on the internal carotid artery ipsilateral to the cerebrovascular
event) should be considered in all:
male patients with a carotid artery stenosis of 50-99% (by NASCET method)
female patients with a carotid artery stenosis of 70-99%.
For all patients, carotid endarterectomy should be performed as soon as the patient is
stable and fit for surgery, ideally within two weeks of event.
Management of patients with stroke or TIA: assessment, investigation, immediate management and secondary prevention
3.1
systems of care
There is a paucity of evidence describing the best systems of care to allow efficient and
rapid assessment and treatment of patients with suspected stroke. There is good evidence,
however, that early assessment, diagnosis and in-hospital treatment of patients with suspected
stroke reduces mortality and morbidity. The availability of effective acute treatment for stroke
necessitates rapid transfer to hospital (see sections 5, 6 and 7).
Two systematic reviews and one Health Technology Assessment (HTA) identified seven barriers
to timely assessment of patients with suspected stroke:11-13
Interventions reported in three systematic reviews and one small non-randomised study as attempts
to speed up presentation of patients with suspected stroke had more impact on in-hospital delays
than out-of-hospital delays.13-16 The range of interventions described to overcome barriers was
varied and included complex, multifaceted interventions, and the interventions may not be
applicable to every healthcare setting.13-16 There was no clear evidence that any intervention in
isolation improved clinical outcome, although multifaceted interventions may be more effective
than single interventions.13 The interventions included:
2++
2++
B
;;
2++
3.2
pre-hospital
2++
2+
Use of MASS was associated with an increase in diagnostic accuracy from 78% to 94%, a decrease
in door to doctor time from 43 to 25 minutes, a decrease in door to computerised tomography (CT)
time from 187 to 127 minutes, and an increase in advanced notification to the hospital from 13%
to 25% of patients.22 Paramedic assessment with MASS was associated with increased telephone
prenotification for acute treatment from 18% to 36%.22 Patients admitted after prenotification had
higher treatment priority (74% compared to 34%), earlier doctor assessment (15 minutes compared
to 31 minutes) and earlier CT scan (94 minutes compared to 144 minutes).22
No comparison of the assessment scales was identified.
C
Standard assessment scales such as FAST or MASS are recommended for pre-hospital
assessment to:
increase the accuracy of the initial stroke diagnosis
assist with more rapid diagnosis
speed up consideration for treatment
assist with more rapid referral to specialist services.
3.3 in-hospital
3.3.1 in-hospital assessment
When used by medical or emergency department staff, the ROSIER (recognition of stroke in the
emergency room) scale (see Annex 6) was superior to CPASS, LAPSS and FAST. In a study of
343 patients use of the ROSIER scale gave accurate diagnosis in 2-3 minutes.20 When internally
validated at a cut-off score greater than zero, the ROSIER scale had a diagnostic sensitivity of
92%, specificity of 86%, PPV=88%, and negative predictive value (NPV) of 91%. Prospective
validation in 173 consecutive patients referred with suspected stroke showed sensitivity of 93%
(89% to 97%), a specificity of 83% (95% CI 77% to 89%), PPV=90% (95% CI 85% to 95%),
and NPV=88% (95% CI 83% to 93%).20
C
2++
Management of patients with stroke or TIA: assessment, investigation, immediate management and secondary prevention
1+
There was insufficient evidence to assess whether acute stroke units with a short period of
admission, roving stroke teams or general neurology units resulted in improved clinical outcomes
for patients with suspected stroke.
A
;;
Patients with TIA requiring admission to hospital should be admitted directly to a stroke
unit staffed by a coordinated multidisciplinary team with a special interest in stroke
care.
Evidence from three studies of very early assessment and initiation of secondary prevention
therapy after TIA or minor stroke strongly suggests that early intervention (within 24 hours)
reduces the risk of early stroke recurrence, although the studies do not directly address the
question of admission.24-26 In a before and after study based on a community cohort, early
active management at a daily TIA clinic was associated with an 80% drop in the risk of stroke
recurrence.24 A study of a 24 hour access TIA clinic from which 74% of patients were sent
home the same day showed that stroke recurrence was less than expected.26
2+
Patients with TIA and minor stroke, who are at high risk of early recurrence, should
undergo specialist assessment and begin treatment promptly.
The routine implementation of care pathways for acute stroke management or stroke
rehabilitation is not recommended where a well organised multidisciplinary model of
care exists.
2+
2++
Management of patients with stroke or TIA: assessment, investigation, immediate management and secondary prevention
4.1
clinical assessment
2++
2+
The revised score ABCD2, which includes history of diabetes, has been extensively tested and
shown to be reliable (see Annex 7).34
C
The ABCD2 score should be used to identify patients who are at highest risk of recurrent
stroke to allow very rapid investigation and treatment.
2++
10
Impairment scales should be considered to help discussion of likely outcomes after stroke
with patients and carers.
;;
Patients in the acute phase of stroke should not be denied treatment based on an impairment
score.
;;
The use of impairment scales may be considered for audit and benchmarking.
2++
2+
4.2.2
Timing of imaging
An HTA explored the optimum timing of brain imaging for patients in the acute phase of
stroke.48 A decision analysis model was developed comparing a scan all patients within 48
hours pathway of care in acute stroke against alternative scan strategies. The most cost-effective
strategy, in terms of least overall cost and most quality adjusted life years (QALYs) after adjusting
for different age ranges, proportions of infarcts and accuracy of CT, was to scan all patients
immediately.
1++
A All patients with suspected stroke should have brain imaging immediately on
presentation.
4.2.3
Modality of imaging
The modality used to image an acute stroke syndrome is determined by patient factors, the
purpose of the imaging and the accuracy of the modality for the suspected stroke syndrome at
the time from ictus at which the patient presents.
CT is widely available, practical, quick and easy to use in ill patients. CT is highly sensitive to
haemorrhage in patients in the hyperacute stage. In patients with ischaemic stroke, particularly
those presenting with mild neurological deficits, CT imaging is often normal in the first few
hours. The accuracy of CT for ischaemic stroke delineation improves after six hours and in
the first few days but it remains less accurate than magnetic resonance imaging (MRI) in
determining site and extent of ischaemic damage, particularly for small lesions and lesions in
the posterior fossa. CT accuracy is reduced beyond one week after the stroke event. In particular,
the discrimination between haemorrhagic and ischaemic stroke origin is impaired as blood
products are absorbed.49,50
2++
2-
Evidence is emerging that MRI may be superior to CT,51 although MRI may be contraindicated
in up to a fifth of patients because they are too ill, confused, dysphasic, have an intraocular or
intracerebral metallic foreign body or have a pacemaker.52
2++
4
MRI with diffusion weighted imaging for ischaemia and gradient echo sequences to detect
haemorrhage is superior to CT scanning for accurate determination of the cause of stroke
syndrome at all time points after presentation, particularly in the first few hours for ischaemia.51
MRI also exhibits less variability in interpretation than CT for ischaemia, including site and
extent. MRI is more sensitive at detecting haemorrhage at this stage.51
2++
MRI with diffusion weighted and gradient echo sequences is recommended (where
available and practical) for the diagnosis of acute stroke syndromes in patients who:
are not severely ill, especially where either neurological deficit is mild and the
clinical likelihood is that the lesion is small or lies in the posterior fossa or
present late (after one week).
The advantages and disadvantages of using CT and MRI are summarised in Annex 8.
11
Management of patients with stroke or TIA: assessment, investigation, immediate management and secondary prevention
4.2.4
4.2.5
2+
4.2.6 teleradiology
Teleradiology links allow electronic transfer of brain images to a remote reader and have been
widely used for several years. One small observational study demonstrated its validity and
reliability compared to reading hard copies on a view box.55
;;
4.3
carotid evaluation
4.3.1 carotid imaging in Patients with carotid territory TIA or Stroke and/or
retinal event
A good quality meta-analysis showed that the most cost-effective diagnostic strategies for carotid
stenosis are those that offer surgery to a larger proportion of patients quickly after the warning
TIA/minor stroke.56 The benefit of performing carotid endarterectomy (CEA) diminishes with time
from the event (see section 11), reinforcing the need for early assessment. The nearer to the time
of stroke/TIA, the less important the actual degree of stenosis is in predicting benefit from CEA.
The time of highest risk for recurrence of stroke/TIA is in the first hours or days after the primary
warning event as stroke related to carotid bifurcation disease relates to stability of the plaque. TIA
carries at least as high a risk of subsequent disabling stroke as minor stroke and its investigation
and treatment should be treated with equivalent urgency. Cost-effectiveness modelling shows
the best strategy is to offer surgery to a larger proportion of patients earlier than is currently the
case in Scotland.56
12
1+
A systematic review found that Doppler ultrasound, computed tomography angiography (CTA),
magnetic resonance angiography (MRA) or contrast-enhanced MRA (CE-MRA) all have high
sensitivities and specificities for diagnosing 70-99% carotid artery stenosis (by the NASCET method,
see Annex 9) in patients with ipsilateral carotid territory ischaemic symptoms.57 Data were too
limited to provide reliable estimates of accuracy for patients with 50-69% stenosis.57 Non-invasive
imaging avoids potential complications of invasive arteriography, but there is consistent evidence
that imaging tests which produce angiographic images have better reproducibility, lower interobserver variation and higher accuracy in assessing/quantifying carotid disease than ultrasound
techniques.57 Of the non-invasive options contrast-enhanced magnetic resonance angiography
(CE-MRA) is the most accurate modality (see Table 1).57 Ultrasound has high sensitivity for detecting
carotid bifurcation disease and a normal ultrasound excludes disease. The poor specificity of
ultrasound for degree of disease when present, high inter-observer variability and insensitivity
for disease at other sites in the extracranial vasculature means that when an initial carotid duplex
examination is abnormal secondary corroborative imaging is required.57
1+
Table 1 Sensitivity and specificity of non-invasive imaging for patients with 70-99% carotid
artery stenosis (by the NASCET method)57
Imaging
modality
Sensitivity
95% CI
Specificity
95% CI
CE-MRA
0.94
0.88-0.97
0.93
0.89-0.96
Doppler
ultrasound
0.89
0.85-0.92
0.84
0.77-0.89
MRA
0.88
0.82-0.89
0.84
0.76-0.97
CTA
0.77
0.68-0.84
0.95
0.91-0.97
All patients with non-disabling acute stroke syndrome/TIA in the carotid territory who
are potential candidates for carotid surgery should have carotid imaging.
;;
;; Duplex ultrasound criteria for grading of carotid disease should be standardised and
regularly audited against another modalities and surgical findings.
Criteria for carotid duplex reporting are shown in Annex 10.
13
Management of patients with stroke or TIA: assessment, investigation, immediate management and secondary prevention
Patients undergoing cardiac surgery who are asymptomatic for stroke or TIA should not
be screened for carotid disease.
4.4
cardiac imaging
An HTA assessed clinical and cost effectiveness of echocardiography in stroke. The metaanalysis confirmed that there is insufficient evidence to make recommendations on the use of
echocardiography in all patients with stroke.62
In the absence of significant carotid disease echocardiography may identify intracardiac thrombus
in stroke patients with atrial fibrillation or evidence of recent myocardial infarction. The distinction
between trans-thoracic and trans-oesophageal echocardiography is unclear. The latter has higher
accuracy for intracardiac thrombus, but may be associated with increased complications in patients
with acute stroke. It is also more expensive, reducing its ultimate cost effectiveness.
There is a lack of evidence to support the routine use of echocardiography to identify atrial septal
abnormalities, mitral valve disease or complex aortic atheroma in patients with stroke. Pick up
rates for cardiac imaging are higher in patients with a clinical suspicion of cardiac disease and
in those without other risk features for stroke. Echocardiography should be considered in those
patients with clinical findings and/or baseline investigations suggesting cardiac disease, and in
cases of cryptogenic stroke.62
No evidence was identified regarding either the use of simple chest radiography for cardiac
assessment or for the use of more sophisticated techniques such as cardiac CT and cardiac MRI
specifically in stroke patients. Evidence was also lacking to support routine cardiac imaging to
identify intracardiac thrombus, the prevalence of which is low in patients with stroke, particularly
those with documented carotid disease (those patients already found to have a potential source
of cerebral atheroembolism).62
Lack of good quality evidence to support cardiac imaging does not necessarily reflect lack of
benefit.
14
The routine use of echocardiography with contrast media for evaluation of patients
with stroke is not recommended.
;;
;;
The use of cardiac CT and MRI should be limited to secondary specialist investigations
for specific problem solving where other tests are inconclusive.
2++
2++
2++
4.5
diagnostic tests
There are good clinical arguments for performing standard haematological or biochemical tests
on patients with a stroke or TIA, although few studies were found on their use or their effect
on management or outcomes.
;;
Standard haematological and biochemical tests such as a full blood count, erythrocyte
sedimentation rate, blood glucose, renal biochemistry and cholesterol level should be
performed on patients with a stroke or TIA as a minimum.
2+
3
15
Management of patients with stroke or TIA: assessment, investigation, immediate management and secondary prevention
5.1
Thrombolysis
1++
Thrombolytic therapy with rt-PA (alteplase 0.9 mg/kg up to maximum 90 mg) administered
within four and a half hours of stroke onset according to protocols stated in the product licence
significantly reduces death and disability at 90 days.65,66
1++
The odds of a favourable outcome (full or nearly full recovery from stroke) are strongly related
to the time to treatment and are significantly greater the earlier that treatment is delivered. The
odds ratio (OR) for favourable outcome is 2.8 (95% CI 1.8 to 4.5) for 090 minutes, 1.6 (95%
CI 1.1 to 2.2) for 91180 minutes, and 1.4 (95% CI 1.1 to 1.9) for 181270 minutes in favour
of rt-PA treatment.67 Administration later than 4.5 hours is associated with an increased risk of
mortality and the risk:benefit ratio has not been established.67
1++
1++
2++
2-
Selection of patients for IV alteplase treatment based on MRI protocols (diffusion-perfusion mismatch
>20% and diffusion-weighted imaging lesion volume less than 120 ml) is associated with similar
proportions of favourable outcomes but reduced proportions of deaths and severe disability when
compared with patients selected by CT alone within the 0-3 hour time window.70-72 Selection by
the same MRI protocols was also associated with similar outcomes in the 3-6 hour window. All
RCTs of IV thrombolysis, however, selected patients on the basis of CT alone.66,67,72
2+
3
A
A
5.1.2
Patients admitted with stroke within four and a half hours of definite onset of symptoms,
who are considered suitable, should be treated with 0.9 mg/kg (up to maximum 90 mg)
intravenous rt-PA.
Onset to treatment time should be minimised.
Systems should be optimised to allow the earliest possible delivery of intravenous
rt-PA within the defined time window.
Streptokinase should not be used for treatment of patients in the acute phase of
stroke.
Intra-arterial thrombolysis
The volume of evidence for intra-arterial thrombolysis is small as relatively few patients are enrolled
in RCTs. Several agents have been examined including rt-PA, urokinase (UK) and recombinant
pro-urokinase (r-proUK). Urokinase and recombinant pro-urokinase are not currently available
in the United Kingdom.
A systematic review included 44 studies of intra-arterial thrombolysis for anterior circulation
stroke, only three of which were RCTs.73 Two of the RCTs compared intra-arterial r-proUK plus
heparin with placebo plus heparin (PROACT I and II, n=220). Thirty three of the studies were
case series of patients treated with urokinase (total n=835).
A further case series of IA urokinase reported a significantly better chance of favourable outcome
compared with matched historical controls.74 Reported recanalisation rates were higher than in
historical control series (around 65% with super-selective administration compared to around
20%), and symptomatic intracerebral haemorrhage rates were 4-10%.
16
2++
Basilar artery occlusive stroke has a high mortality (approximately 90%) without
recanalisation.73
2++
In a systematic review of case series of intravenous (n=76) and intra-arterial (n=344) treatment
recanalisation was reported more often with IA treatment but survival rates and favourable
outcomes were similar.75 Treatment was started within 12 hours of symptom onset in 73-77%
of patients, but within six hours in 29%.75 One RCT of IA urokinase included only 16 patients.
Four out of eight patients receiving UK had good outcome compared with only one out of
eight in the control group.76 Combined IA alteplase and treatment with the glycoprotein IIb/IIIa
inhibitor abciximab achieved higher recanalisation rates and a higher proportion of favourable
clinical outcomes compared to a historical control series receiving IA alteplase alone, with or
without stenting in either group.77
12+
2-
Recanalisation rates are known to be significantly poorer with certain sites of occlusion (for
example, carotid T occlusions) and reocclusion more common with others (for example, basilar
artery). Combined IV-IA treatment can be planned from the outset. Since recanalisation is the
major determinant of successful outcome in stroke patients treated with IV thrombolytic therapy,
and the majority of recanalisation occurs within two hours of drug administration, rescue IA
therapy is a logical development of treatment.70
One RCT comparing IV plus IA alteplase (IV 0.6 mg/kg plus IA maximum 20 mg) with placebo
plus IA alteplase, two retrospective and two prospective case series (n=63) were included in a
systematic review.73 A further prospective study of IV plus IA therapy reported a higher proportion
of favourable clinical outcomes than historical controls from published IV thrombolysis RCTs
with similar rates of symptomatic intracerebral haemorrhage.78
A prospective case series reported comparable outcomes in patients treated with standard IV
alteplase who recanalised (as defined by ultrasound) and those who failed to recanalise after
30 minutes of IV treatment who subsequently received IA alteplase.79
B
Intra-arterial thrombolysis may be considered for patients with proximal middle cerebral
artery occlusion or basilar artery occlusion that presents beyond four and a half
hours.
Treatment should be delivered within six hours of symptom onset in patients with
middle cerebral artery occlusion.
1+
2++
23
Aspirin 300 mg daily should be commenced within 48 hours of ischaemic stroke and
continued for at least 14 days.
;;
In patients with dysphagia aspirin (300 mg) should be administered rectally or by enteral
tube.
1++
17
Management of patients with stroke or TIA: assessment, investigation, immediate management and secondary prevention
Guidelines are available covering the identification and management of dysphagia following
stroke,7 and for administration of medication to patients with enteral feeding tubes or swallowing
difficulties.81
Standard protocols for IV and IA thrombolytic therapy presently advise avoidance of aspirin for
24 hours after thrombolytic drug treatment.80
Aspirin for preventing recurrent stroke is discussed in section 9.1.
;;
1+
2-
Insufficient evidence exists to support the routine use of the combination of aspirin and
clopidogrel for treating patients in the acute phase of stroke.
5.3 anticoagulants
The administration of anticoagulants is contraindicated during the first 24 hours after IV
thrombolytic therapy.83 Although recanalisation may be more successful, the risk of haemorrhage
increases. Evidence on adjunctive anticoagulation is limited and neither the safety nor efficacy
has been established.83
18
1++
1++
In patients with atrial fibrillation, weight-adjusted high dose LMWH (dalteparin 100 iu/kg) was
not superior to aspirin in preventing early stroke recurrence and carried a significantly higher
risk of extracerebral haemorrhage.87
1+
Symptomatic and asymptomatic venous thromboembolic events are highly significantly reduced
by all heparin treatments. Deep vein thrombosis (DVT) is avoided in 281 patients for every
1,000 treated and pulmonary thromboembolisms (PTE) are avoided in four patients per 1,000
treated.84 LMWH and heparinoids are associated with a significantly greater reduction in DVT
than UFH without any additional hazard.86 Enoxaparin 40 mg once daily is superior to UFH
5,000 units twice daily and is not associated with any increase in bleeding complications or
difference in mortality.88
1++
1+
Warfarin
In one trial 100 patients received warfarin within two weeks of stroke onset and none had
haemorrhagic worsening.89 Large, disabling strokes were under-represented. An arbitrary time
limit of two weeks is recommended for delaying warfarin treatment for AF following acute
stroke.89
5.3.5
1++
1+
Fibrinogen-depleting agents
Fibrinogen-depleting agents did not reduce death or dependence when given within six hours
of stroke onset.90 There was no benefit from ancrod given within six hours of stroke onset, and
a significant increase in symptomatic and asymptomatic intracranial haemorrhage.91 When all
ancrod trial results are considered, no benefit on death or dependence was evident (OR=93;
95% CI 0.77 to 1.12, calculated from primary data).
A
1+
The routine use of anticoagulants (UFH, LMWH, heparinoids, oral anticoagulants, direct
thrombin inhibitors, fibrinogen-depleting agents) is not recommended for the treatment
of acute ischaemic stroke.
Anticoagulants are not recommended in patients with progressing stroke.
For patients in atrial fibrillation following stroke, anticoagulation with warfarin can be
introduced early in patients with minor stroke or TIA, but should be deferred for two
weeks after onset in those with major stroke.
19
Management of patients with stroke or TIA: assessment, investigation, immediate management and secondary prevention
5.4 Neuroprotectants
Many agents have been studied for a potential neuroprotective effect in patients with stroke.
There are systematic reviews of glutamate antagonists,92 calcium antagonists,93, 94 the free radical
scavenger tirilazad,95 vinca alkaloids,96 oral citicoline,97 the sodium antagonist lubeluzole,98
corticosteroids,99 methylxanthine derivatives (pentoxiffyline, propentofylline and pentofylline),100
aminophylline,101 and piracetam102 and phase III RCTs of the free radical spin trap NXY 059,103
5HT1a agonist repinotan,104 neutrophil chemotaxis inhibitors enlimomab105 and UK-279,276,106
magnesium,107 nalmefene,108 diazepam,109 chlomethiazole,110 cerebrolysin,111 and the free radical
scavenger edaravone.112
These agents have widely differing pharmacological actions. For the majority of agents, there was
no evidence of benefit or harm. The exceptions are:
Definite harm (increase in odds of death or dependence)
tirilazad (OR=1.23; 95% CI 1.01 to 1.50)95
enlimomab (adjusted p=0.004 for worse distribution of Rankin grade).105
1++
1+
Possible harm
1+
1++
1+
For other agents, there was insufficient evidence to define benefit or harm.
;;
5.5
Neuroprotectant agents should be used only within the context of randomised controlled
trials.
5.5.1 mannitol
A systematic review of mannitol in acute stroke included only one RCT of 77 patients, reported
in 1978.113 Temporary reduction in intracranial pressure (ICP) in patients with cerebral oedema
in massive middle cerebral artery (MCA) infarction (malignant MCA syndrome) was reported, but
there was no effect on clinical outcomes.
5.5.2
Hypertonic saline
Hypertonic saline (10%) reduced ICP (and elevated cerebral perfusion pressure) for up to
four hours after failure of mannitol in space occupying ischaemic stroke or ICH in eight
patients.114
20
1++
5.5.3 glycerol
A systematic review of 10 RCTs (n=945) of glycerol to reduce raised ICP showed a trend
towards reduced mortality within the treatment period (typically seven days, OR=0.78; 95%
CI 0.58 to 1.06), which was significant when analysis was restricted to five truly randomised
trials. 115 There was no reduction in mortality at the end of follow up.116 Only two trials reported
functional outcomes and there was no significant effect seen (OR=0.73; 95% CI 0.37 to 1.42).
A subsequent retrospective cohort study of 442 patients found no effect on mortality, and
significantly increased mortality when glycerol was co-administered with corticosteroids.115
1++
2+
23
CORTICOSTEROIDS
A systematic review of seven trials of corticosteroids in acute stroke showed no evidence of
benefit.99 In a small retrospective study of corticosteroids in acute stroke 30 day mortality was
increased.115
1++
2-
1++
1+
For individuals aged up to 60 years who suffer an acute MCA territory ischaemic stroke
complicated by massive cerebral oedema, surgical decompression by hemicraniectomy
should be offered within 48 hours of stroke onset.
It is uncertain whether selected patients older than 60 years will benefit from surgical
decompression.
21
Management of patients with stroke or TIA: assessment, investigation, immediate management and secondary prevention
Mechanical clot disruption (including clot maceration by guidewire, clot snaring and balloon
angioplasty) may achieve recanalisation in patients with persistent MCA or ICA occlusion after
standard IV or IA rt-PA.123,124 Immediate recanalisation was achieved in 38% of patients and
final recanalisation in 75% compared to rates of 6% and 72% for simple clot penetration by
microcatheter.123 Bleeding risks did not appear to be increased.
5.7.2
2+
2-
1+
22
1+
1-
Guidelines are available covering the identification and management of dysphagia following
stroke,7 and for administration of medication to patients with enteral feeding tubes or swallowing
difficulties.81
;;
Patients with ischaemic stroke on prior statin therapy should continue treatment, via a
nasogastric tube, if necessary.
23
Management of patients with stroke or TIA: assessment, investigation, immediate management and secondary prevention
6.1
haematoma evacuation
The evidence for haematoma evacuation and clot lysis for primary intracerebral haemorrhage
is inconsistent due to the small size and heterogeneous entry criteria of most RCTs in this area,
compounded by the very long time span over which these RCTs have been conducted.
Three systematic reviews of ICH evacuation each make different judgements on data from
RCTs.129-131 One systematic review of four RCTs (n=354) included data from an RCT conducted
in 1961, before use of CT to confirm diagnosis.130 A metaanalysis of seven RCTs and two quasirandomised trials (total n=1,258), also included data from non-randomised trials.131 There was a
non-significant trend towards reduced mortality (OR=0.84; 95% CI 0.67 to 1.07) and reduced
death or dependence (OR=0.82; 95% CI 0.63 to 1.06) for surgical intervention.91 One trial
contributed the greatest number of patients (1,033) to this systematic review, but covered a wide
range of interventions in a heterogeneous population over an extended time period.132
1++
1+
Other analyses from STICH (Surgical Treatment for IntraCerebral Haemorrhage) indicate an
extremely wide variation in the rate of surgical intervention by country.133 More than 75% of
surgical interventions were by craniotomy.
In the single RCT published since the 2006 systematic review, with intervention within eight hours
of onset, there was a non-significant reduction in death (48% versus 57%) and good functional
outcome was significantly more frequent (33% versus 9%).134
1+
1+
6.2 thrombolysis
Intraventricular haemorrhage (IVH) is an established independent risk factor for poor prognosis
in ICH. External ventricular drain (EVD) placement allows monitoring and intracranial pressure
management.136
24
A single RCT of patients with PICH and hydrocephalus requiring EVD, randomising to urokinase
(n=7) or placebo was identified.137 Intraventricular urokinase speeds up radiological resolution
of IVH clots. Treatment reduced the half-time of radiological resolution by a mean of 3.8 days,
from 8.5 in the placebo group to 4.7 in the urokinase treated group The trial was too small to
assess the effect on functional outcomes and mortality and did not have a non-surgical control
group for comparison.
1-
Case series identified by a systematic review report more favourable outcomes than historical
controls, where used, with IVH lysis either by rt-PA or urokinase administered either continuously
or intermittently via an external ventricular drain.136 There was no reported increase in risk of
haemorrhage or other adverse outcomes.
6.3
haemostatic therapies
RCTs of haemostatic therapy are justified on the basis of natural history studies that identify
the prognostic importance of early haematoma expansion in the first four hours after symptom
onset, and the association of expansion and larger haematoma volume with poor outcome.
A systematic review of four RCTs showed that, despite methodological limitations, recombinant
factor VIIa significantly reduced the risk of death or dependence within 90 days of PICH.138
1++
Preliminary results from a study of recombinant factor VIIa in acute haemorrhagic stroke
treatment showed reductions in haematoma volume growth similar to previous studies but
failed to show any benefits on death or dependency at 90 days with 20 mcg/kg or 80 mcg/kg
of factor VIIa compared to placebo.139
;;
6.4
6.4.1 corticosteroids
A systematic review of corticosteroids in primary intracerebral haemorrhage included five RCTs,
all of which used dexamethasone 4-12 mg for 2-16 days.140 Two trials conducted in the 1970s
did not confirm the diagnosis radiologically and in one, 28% of patients were found to have
had ischaemic stroke at autopsy.140
1++
At one month, dexamethasone had no significant effect on mortality (RR=1.14; 95% CI 0.91
to 1.42) or death or dependence (RR=0.95; 95% CI 0.83 to 1.09). A non-significantly higher
number of complications was reported in patients treated with dexamethasone.140
B
6.4.2 mannitol
One RCT compared IV mannitol infusions to placebo for control of raised ICP in spontaneous
primary intracerebral haemorrhage.141 Four-hourly infusions of 100 ml of 20% mannitol for
five days in patients with spontaneous supratentorial ICH did not affect one-month mortality
(16 out of 65 mannitol-treated patients compared to 16 out of 63 untreated patients, OR=0.96;
95% CI 0.40 to 2.31 as calculated by guideline development group) or three month death or
dependence on the Barthel Index (39 out of 65 patients compared to 34 out of 63, OR=1.28;
95% CI 0.60 to 2.74).
B
1+
Intravenous mannitol should not be used routinely for treatment of raised intracranial
pressure in patients with primary intracerebral haemorrhage.
25
Management of patients with stroke or TIA: assessment, investigation, immediate management and secondary prevention
1++
A case series reported the rate of ICH in patients with CVT at between 0% and 5.4%.143
Anticoagulation resulted in non-significant reductions in death or dependency at three months
and non-significant reductions in death from any cause.
;;
Anticoagulation with warfarin (target INR 2-3) should usually be continued for 6-12
months following the recommendations for treatment of deep vein thrombosis and
pulmonary thromboembolism.
7.1.2 thrombolysis
A Cochrane review of thrombolysis for cerebral venous thrombosis identified no RCTs.145
A retrospective non-randomised study of local urokinase suggested that thrombolysis in
cerebral venous thrombosis appears safe but its routine clinical use cannot be supported.146 It
may be indicated in selected cases where there is ongoing clinical deterioration despite other
therapy.142,147
2++
4
26
Dissections of the vertebral arteries are less well defined but occur in 1 to 1.5 per 100,000 per
year in a hospital population series.148 Multiple arteries are involved in 28% of patients and the
vertebral arteries in around 25%. The risk of recurrence of carotid dissection is around 1% per
annum. The subsequent risk of stroke was around 1% and the risk of TIA around 2% over a
follow-up period of 31 months in one case series.148
One long term follow-up study over six to seven years showed annual rates of ipsilateral stroke
of 0.7% and of any stroke of 1.4% for those left with permanent carotid stenosis or occlusion.
Following transient stenosis with complete or partial recovery (<50% stenosis), the annual rate
of ipsilateral stroke after treated carotid dissection was 0.3% and of any stroke was 0.6%.149
The most likely cause of stroke in cervical artery dissection is embolism from the dissection
flap but some cases may be due to haemodynamic compromise from the dissection itself.150 It
is important to be aware of the possibility of intracranial extension of the dissection resulting in
subarachnoid haemorrhage. This diagnosis should be excluded in the usual way if symptoms are
suggestive prior to initiating treatment with antiplatelets or anticoagulation.151
3
4
A Canadian multicentre prospective series of 116 patients (67 vertebral and 49 carotid dissections),
found a 15% risk of recurrent TIA, stroke or death at one year of follow up. The event rate for
patients on anticoagulation was not significantly different to those on aspirin.153
;;
;;
Further imaging of the cervical arteries may be required to assess healing or progression
of the vascular lesion.
;;
Stenting may be considered if recurrent ischaemic events occur despite medical therapy
or where traumatic dissection has occurred with a high risk of stroke.
27
Management of patients with stroke or TIA: assessment, investigation, immediate management and secondary prevention
physiological monitoring
Little evidence was identified relating to intensity of physiological monitoring. The studies that have
been done looked at different individual components of physiological monitoring. Trials addressing
intensity tended to compare continuous monitoring with four to six times daily measurements
for a period of 48 to 72 hours. The patients included all had ischaemic strokes. The studies did
not address monitoring of conscious level or pulse rate as individual items. Patients who had
received thrombolysis were not included.
A prospective study of 268 patients with ischaemic stroke comparing continuous monitoring
(blood pressure, electrocardiogram, oxygen saturation, temperature) for 72 hours in a stroke
unit compared to routine care (less intense monitoring) showed that more intensive care led to
a 2.5 fold increase in the probability of a good outcome at discharge. This may be due to earlier
detection and correction of complications.157
2+
A small RCT (54 patients) compared a stroke care monitoring unit (SCMU) to conventional stroke
unit care. Monitoring for 48 hours was associated with a lower proportion of patients who died
or had a poor outcome at three months. The average length of stay was shorter for the SCMU (16
5 days versus 25 7 days).158
1+
Continuous or frequent physiological monitoring in the acute phase of stroke identifies adverse
physiological events that may require intervention.
;;
;;
Monitoring should be balanced against other important aspects of stroke unit care,
particularly early mobilisation and rehabilitation.
There are limited data available on the use of intravenous fluids in acute stroke. No studies were
identified to determine the most effective type or volume of infusion.
28
Data extrapolated from evidence in patients with hyperglycaemia support avoidance of dextrose
in the early post-stroke phase.160
1+
The available evidence consistently showed no benefit from haemodilution in the acute phase of
stroke, rather there was a modest trend towards harm, except in patients with polycythaemia.161
A meta-analysis of studies of haemodilution using plasma expanders (dextran, hydroxyethyl
starch and albumin) compared to standard fluid replacement therapy found no evidence of
benefit over standard regimens in terms of reducing mortality or improving functional outcome
in survivors.161
1++
Whilst not designed as an efficacy study, a study of the effects of hydroxyl ethyl starch showed
no benefit over crystalloid solution.162
1-
The use of standard IV saline infusion was associated with a significant fall in plasma glucose
within the first 24 hours after acute ischaemic stroke.160
1+
A small study of 34 stroke patients with dysphagia randomised to either intravenous or subcutaneous
fluid replacement therapy suggests that the latter will satisfactorily maintain plasma osmolality
within normal limits.163
2+
For patients in whom IV fluids are not appropriate, subcutaneous fluids can be used
to maintain plasma osmolality within the normal range.
2-
1++
Blood pressure elevation using either phenylephrine or dexamphetamine has been associated
with reduction in infarct size. A small study (45 patients) suggests that blood pressure elevation
with dexamphetamine may improve early outcome.167,168
1-
Small studies looking at surrogate markers of cerebral blood flow, such as SPECT, showed that
both perindopril or losartan given within 2-7 days of stroke onset do not lower cerebral blood
flow.169,170 One study of perfusion weighted MRI suggested that phenylephrine may reduce infarct
size.168 These interventions have not been tested in RCTs with clinical end points.
1+
Compared to placebo, candesartan given early after acute stroke appears to be associated
with a reduction in further events despite a lack of effect on blood pressure.171 The study was
underpowered and did not meet its primary end points, so no firm conclusions on BP lowering
can be made.171
1-
1++
Nimodipine has a negative effect on outcomes associated with a reduction in diastolic blood
pressure but not with lowering of systolic blood pressure.169
1+
Lisinopril appears to be safe in the acute phase of stroke but its clinical benefit is uncertain. Given
orally to patients with hypertension (140/90 mmHg), 5 mg within 24 hours of stroke onset
significantly lowered blood pressure within four hours of administration. No difference was found
in neurological or functional outcomes at 90 days.173
1+
29
Management of patients with stroke or TIA: assessment, investigation, immediate management and secondary prevention
Ongoing trials are exploring whether BP should be lowered acutely following stroke, and whether
antihypertensive therapy should be continued or stopped in the first few days after stroke.174,175
A
Blood pressure should not be actively managed as a routine in patients in the acute
phase of ischaemic stroke.
;;
;;
8.2.4 feeding
Oropharyngeal dysphagia affects a large proportion of patients in the acute phase of stroke.
Swallowing difficulties can result in serious complications such as aspiration pneumonia,
undernutrition, dehydration and missed medication. It is important that early screening for
symptoms of dysphagia is carried out on admission and before giving food, drink or administering
oral medications.
Guidelines are available on the identification and management of dysphagia following stroke,7
and for the administration of medication to patients with enteral feeding tubes or swallowing
difficulties.81
In patients who have difficulty taking food and oral medication safely due to a low consciousness
level and/or the presence of dysphagia, nutrition may be provided via a nasogastric (NG) tube
or a percutaneous gastrostomy (PEG) tube. There is no clear guidance on how quickly feeding
should be initiated and which feeding tube is more suitable.
30
1+
3
1+
A multicentre RCT investigated the timing and method of enteral feeding for patients with
dysphagia in the acute phase of stroke. There was no statistically significant difference between
early and delayed feeding on mortality and morbidity. Early tube feeding showed a non-significant
absolute risk reduction in death of 5.8% (95% CI -0.8 to 12.5; p=0.09).182 There was a borderline
statistically significant increase of 7.8% in the absolute risk of death or poor outcome in the use of
PEG compared with NG (95% CI 0.0 to 15.5; p= 0.05).182 An RCT investigating the routine use
of oral nutritional supplements recruited non-dysphagic patients who were adequately nourished
prior to their stroke.183 No significant difference was identified between the study groups, although
no evidence was identified for withholding the focused use of nutritional supplements in patients
recognised at risk through nutritional screening. 183
1++
1-
1++
Hyperbaric oxygen therapy for patients with acute ischaemic stroke is not recommended
outwith the setting of a clinical trial.
2+
A systematic review did not identify any evidence that either physical cooling or the use of
medication to lower temperature has an effect on outcome.189
1++
Three small trials studying the effect of paracetamol (166 patients in total) and ibuprofen (24) in
lowering temperature in patients with acute stroke showed the limitations of antipyretic medications
in achieving normothermia for patients with fever.190-192 Treatment with a daily dose of 6,000 mg
of paracetamol resulted in a small reduction in body temperature.191
1-
31
Management of patients with stroke or TIA: assessment, investigation, immediate management and secondary prevention
1-
Early mobilisation
A systematic review found good long term benefit from early neurological rehabilitation as part
of routine stroke care. Early mobilisation and early neurorehabilitation were not clearly defined.
Early was from one to three days and mobilisation was any physical activity of the body initiated
either by the patient or by the environment (for example, positioning in bed, sitting on the edge
of the bed, or standing up). Studies using comparisons between stroke units and general wards
showed that stroke units had better outcomes, although the practice of getting patients out of bed
within 24 hours in one of the studies may be confounding.193
A
1++
Early mobilisation, including positioning in bed, sitting on the edge of the bed, or standing
up should be considered for patients within the first three days after a stroke.
32
1++
1+
2+
3
1++
2+
2-
33
Management of patients with stroke or TIA: assessment, investigation, immediate management and secondary prevention
1++
Clopidogrel was more effective than aspirin alone in reducing the combined end point of ischaemic
stroke, myocardial infarction (MI) or vascular death (RRR=8.7%; 95% CI 0.3 to 16.5; p=0.043;
ARR=0.51%; NNT=196 to prevent one event over a year) except in the subgroup recruited with
prior stroke where there was no significant benefit of clopidogrel over aspirin (RRR=7.3%; 95%
CI -5.7 to 18.7; p=0.26; ARR=0.56%; NNT=179 to prevent one event over a year).207
1++
34
1++
1-
1++
1++
An RCT in 20,332 patients followed up for a mean of 2.5 years, compared aspirin 25 mg plus
dipyridamole extended release 200 mg twice daily with clopidogrel 75 mg with the primary
outcome of first recurrent stroke. The net risk of recurrent stroke did not differ between the two
groups (11.7% in the aspirin/dipyridamole group compared to 11.4% in the clopidogrel group;
95% CI 0.95 to 1.11).209
1+
1+
Low-dose aspirin (75 mg daily) and dipyridamole (200 mg modified release twice daily)
should be prescribed after ischaemic stroke or TIA for secondary prevention of vascular
events.
;;
;;
The combination of aspirin and clopidogrel is not recommended for long term secondary
prevention of ischaemic stroke or TIA.
9.1.2 triflusal
A meta-analysis showed no significant difference between aspirin and triflusal for secondary
prevention of serious vascular events, including ischaemic stroke and TIA.211 Two doses of
triflusal were used in the included trials (600 mg and 900 mg). The confidence intervals of the
meta-analysis were wide and cannot exclude the possibility that triflusal is significantly better or
worse than aspirin. Triflusal was associated with a significantly lower risk of minor and major
bleeding episodes but had a higher risk of non-haemorrhagic gastrointestinal episodes.211 A
significant number of patients discontinued the study medication early for reasons other than the
primary outcome.
1++
9.2
statins
There is consistent evidence from two systematic reviews212, 213 and a subsequent RCT214
that treatment with a statin significantly reduces the relative risk of ischaemic stroke by 21%
(OR=0.79; 95% CI 0.73 to 0.85) although stroke death is not significantly reduced (OR=0.91;
95% CI 0.76 to 1.10). The effect was seen without an associated increase in haemorrhagic stroke
(OR=0.90; 95% CI 0.65 to 1.22). The reduction in stroke risk is proportional to the lowering of
low density lipoprotein (LDL) cholesterol and occurs irrespective of baseline cholesterol level.215
Treatment with a statin also significantly reduces coronary events and all-cause mortality.215
1++
Atorvastatin at 80 mg daily given to patients with recent stroke or TIA reduced ischaemic stroke
and cardiovascular events after TIA or ischaemic stroke. Over a median follow up of 4.9 years
the absolute risk reduction in fatal or non-fatal stroke was 2.2% (95% CI 0.2 to 4.2%) giving an
NNT over five years of 45 to prevent one fatal or non-fatal stroke. There were more haemorrhagic
strokes in the atorvastatin group giving a hazard ratio of 1.66 (95% CI 1.08 to 2.55). The absolute
risk increase was 0.9% giving a number needed to harm (NNH) of 107 over five years.215
35
Management of patients with stroke or TIA: assessment, investigation, immediate management and secondary prevention
Simvastatin at 40 mg daily given to patients with prior cerebrovascular disease reduced the
incidence of any major vascular event (RRR=20%; 95% CI 8 to 29%; p=0.01), but did not
reduce the risk of subsequent stroke.215
1++
A systematic review pooled 8,832 individual patients with prior cerebrovascular disease treated
with a statin, including simvastatin (40 mg), atorvastatin (80 mg) and pravastatin (40 mg).216 The
overall relative risk reduction for any type of stroke in statin users was 0.88 (95% CI 0.78 to
0.99). The relative risk of ischaemic stroke is reduced to 0.8 (95% CI 0.70 to 0.92) but there is an
increased risk of haemorrhagic stroke with a hazard ratio of 1.73 (95% CI 1.19 to 2.50).
1++
A statin should be prescribed to patients who have had an ischaemic stroke, irrespective
of cholesterol level.
Atorvastatin (80 mg) should be considered for patients with TIA or ischaemic stroke.
A Other statins (such as simvastatin 40 mg) may also be considered as they reduce the
risk of major vascular events.
A
Statin therapy for prevention of further vascular events post-haemorrhagic stroke is not
recommended routinely unless the risk of further vascular events outweighs the risk of
further haemorrhage.
9.3 anticoagulants
9.3.1
1++
1+
36
1++
1+
1++
Despite the increased incidence of AF and the higher stroke risk in the elderly (>75 years)
anticoagulation is underused in this age group. One trial comparing dose-adjusted warfarin (INR
2.0-3.0) to aspirin 300 mg daily in a group of octogenarians found more adverse events in the
aspirin group (33% compared to 6%, p=0.002).221 Compared to aspirin 75 mg in patients aged
>75 years with AF, warfarin significantly reduced the risk of stroke, arterial embolism or other
ICH (21 events with warfarin, 48 events with aspirin; yearly risk 1.8% versus 3.8%; RRR=0.48
95%, CI 0.28 to 0.8; p= 0.003; ARR=2%; 95% CI 0.7 to 3.2; NNT=50 over one year).222 This
benefit takes into account any intracranial haemorrhages and occurs without any increase in the
risk of extracranial haemorrhage (1.4% warfarin, 1.6% aspirin per annum).
A
Patients with ischaemic stroke or TIA who are in atrial fibrillation should be offered
warfarin with target INR 2.0-3.0.
1+
1-
No evidence was identified to support benefit from the routine use of aspirin in addition to
warfarin.
9.4
Antihypertensives
There is a well established link between blood pressure and stroke,223 and between blood pressure
treatment and reduction in stroke risk.224
Current guidelines for management of hypertension from the British Hypertension Society suggest
systolic BP should be treated to <140 mm Hg and diastolic BP to <85 mm Hg,225 with a target
of 130/80 mm Hg for patients with diabetes.226
While many studies have included small numbers of patients with previous stroke, there have
been relatively few studies looking at secondary prevention in patients presenting with ischaemic
or haemorrhagic stroke.
A systematic review identified seven RCTs looking at prevention of recurrent vascular events in
patients with previous stroke or TIA.227 Lowering BP or treating established hypertension reduced
stroke (OR=0.76; 95% CI 0.63 to 0.92), non-fatal stroke (OR=0.79, 95% CI 0.65 to 0.95),
myocardial infarction (OR=0.79; 95% CI 0.63 to 0.98) and total vascular events (OR=0.79; 95%
CI 0.66 to 0.95). No effect was seen on vascular or all-cause mortality. There was heterogeneity
in the studies due to the class of drugs used, with beta blockers having no discernible effect.
Reduction in stroke was related to the difference in systolic BP between treatment and control
groups (p=0.002).
One study of patients with a history of stroke (ischaemic or haemorrhagic) looked at blood
pressure lowering with perindopril (an ACE inhibitor) alone, perindopril in combination with
indapamide (a thiazide) or placebo. Patients unable to tolerate the combination were excluded
during run in. BP lowering with perindopril and indapamide in combination resulted in a
reduction in recurrent stroke and major vascular events. Five years of treatment resulted in one
less fatal or non-fatal vascular event for every 11 patients treated (95% CI 9 to 16). BP lowering
with a combination of perindopril and indapamide was shown to be safe in patients who have
had a stroke or TIA and who are either hypertensive or normotensive.228
In an open label study comparing eprosartan and nitrendipine for secondary prevention of
stroke/TIA both drugs achieved target BP reductions. The cerebrovascular and cardiovascular
end points were not significantly different.229
A
All patients with a previous stroke or TIA should be considered for treatment with an
ACE inhibitor (for example, perindopril) and thiazide (for example, indapamide)
regardless of blood pressure, unless contraindicated.
1++
1+
1+
37
Management of patients with stroke or TIA: assessment, investigation, immediate management and secondary prevention
9.5
2+
9.6
carotid endarterectomy
The role of carotid endarterectomy is discussed in section 11.
2++
A single RCT comparing anticoagulant and antiplatelet therapy in patients with cryptogenic stroke,
which included sub-analysis of patients with PFO (present in 39% of patients with cryptogenic
stroke), randomised patients between 30 and 85 years of age to either warfarin or aspirin.237 The
rate of recurrent stroke or death at two years was 14.3% in those with PFO, compared to 12.7%
without (OR=0.86; CI 0.41 to 1.80). There was no significant difference in event rates between
patients with cryptogenic stroke and PFO treated with aspirin (17.9%, n=56) and those treated
with warfarin (9.5%, n=42; hazard ratio, HR=0.52; 95% CI 0.16 to 1.67; p = 0.28). As this was
a substudy, it was not powered to demonstrate superiority of one therapy in patients with PFO.
1-
Although no RCTs of closure of PFO compared to medical therapy were identified, evidence
from a systematic review of case series suggests that percutaneous transcatheter closure of PFO
may reduce the risk of recurrent stroke more than medical therapy alone. The review identified
six studies (895 patients) looking at medical management of PFO, and 10 studies (1,355 patients)
looking at transcatheter closure.238 Medical therapy varied by type and dose (aspirin, warfarin and
clopidogrel). There was a trend towards an increased incidence of recurrent events with increasing
age. With medical therapy, the incidence of stroke or TIA after one year of follow up ranged from
3.812%. With transcatheter closure of PFO, TIA or stroke incidence was 0-4.9%. The incidence
of major or minor procedural complications was 1.45% and 7.9% respectively. Patients in the
medically treated groups were at higher prevalence of risk factors for atherosclerosis.
38
Patients with cryptogenic stroke and PFO should be treated with antiplatelet therapy
to reduce the risk of recurrence.
Transcatheter closure of PFO may be considered for patients with recurrent cryptogenic
stroke on optimal medical management.
39
Management of patients with stroke or TIA: assessment, investigation, immediate management and secondary prevention
1++
The use of aspirin following ICH is not recommended to prevent further vascular events
when the risk of recurrence is low.
The use of aspirin following ICH may be considered when there is a high risk of cardiac
ischaemic events.
2++
10.3 anticoagulants
No clinical trials were identified describing the use of anticoagulants after ICH. A decision analysis
based on assumptions of risk of recurrent ICH and the risks associated with aspirin and warfarin
therapy concluded that anticoagulation cannot be safely recommended for atrial fibrillation
following either a lobar or deep ICH unless an individual is at very high risk of ischaemic stroke.241
Aspirin may be a reasonable strategy for treating those with a prior deep ICH and an intermediate
or higher risk of ischaemic stroke.241
D
;;
40
10.4
statins
An RCT of statin therapy to prevent recurrent stroke included 4,731 patients, 93 of whom had
haemorrhagic stroke. Forty five patients were recruited to the treatment arm and received 80 mg
of atorvastatin and forty eight received placebo.214 Individual outcomes for these patients were not
reported and the numbers were too small to be meaningful. In the treatment group there were 218
ischaemic strokes and 55 haemorrhagic strokes compared to 278 ischaemic and 33 haemorrhagic
strokes in the placebo group. There were more haemorrhagic strokes in the atorvastatin group
giving a hazard ratio of 1.66 (95% CI 1.08 to 2.55). The absolute risk increase was 0.9% giving
an NNH of 107 over five years.
1++
There are risks and benefits of statin treatment in this population and the potential risk of
intracerebral haemorrhage should be considered (see section 9.2).
A
Statin therapy after haemorrhagic stroke is not routinely recommended unless the risk
of further vascular events outweighs the risk of further haemorrhage.
;;
In this group of patients, their overall vascular risk profile should be taken into
account when considering the risks and benefits of statin.
41
Management of patients with stroke or TIA: assessment, investigation, immediate management and secondary prevention
11 Carotid intervention
11.1 Carotid endarterectomy
11.1.1
1++
Subsequent studies also found no evidence to support the traditional view that endarterectomy
should be delayed in patients with minor stroke who are neurologically stable.244, 245 In patients
with 50-69% stenosis (by NASCET method) the only statistically significant benefit occurred if
surgery was performed within two weeks of the event (see Table 2).243
1+
Table 2 Number needed to treat to prevent one ipsilateral stroke at five years in patients with
50% stenosis by NASCET method243
Time of surgery post primary event
NNT
within 2 weeks
2 to 4 weeks
10
4 to 12 weeks
18
125
A systematic review of operative risk in relation to timing of surgery did not demonstrate an excess
risk from early surgery compared to late surgery in neurologically stable patients.246
1++
Published risks from carotid endarterectomy did not significantly change between 1985 and
2001,247 with a 1.4%-2.9% risk of death and a 4.2%-6.5% risk of death or stroke combined.
Reported complication rates were lower in studies where non-neurologists made the postoperative
assessment.
In patients with a progressing neurological deficit or stuttering stroke, there is a lack of evidence
about whether surgery should be performed as an emergency and no recommendation can be
made to support this.
Pooled analysis showed greater benefit of CEA in older patients (in patients with 50-99% stenosis
by NASCET method).243 The absolute risk reduction with surgery in terms of five-year cumulative
risk of ipsilateral carotid ischaemic stroke and any stroke or death within 30 days after surgery
was 19.2% (95% CI 10.2% to 28.2%) in those aged 75 or over, 8.6% (95% CI 4.2% to 13.0%)
in those aged 65-74 and 5.6% (95% CI 1.6% to 9.6%) in those less than 65 years of age. This is
despite an increase in postoperative mortality in older patients.248
Only 10% of patients in the analysis were over 75 years of age and very few were over 80
years.
42
1++
11 CAROTID INTERVENTION
Meta-analysis and subgroup analysis of pooled data show that women gain less benefit than men
from carotid endarterectomy (for patients with 50-99% stenosis).243, 248 The NNT to prevent one
stroke at five years is nine for men and 36 for women. There is clear benefit in women with 7099% stenosis but not in those with 50-69% stenosis.243 This is driven by a higher operative risk
in women243, 248 and more rapid reductions in risk of stroke recurrence on medical therapy with
time in women.243
A
All patients with carotid artery territory stroke (without severe disability, mRS2)
or transient ischaemic attack should be considered for carotid endarterectomy as soon
as possible after the index event.
Carotid endarterectomy (on the internal carotid artery ipsilateral to the cerebrovascular
event) should be considered in all:
male patients with a carotid artery stenosis of 50-99% (by NASCET method)
female patients with a carotid artery stenosis of 70-99%.
For all patients, carotid endarterectomy should be performed as soon as the patient is
stable and fit for surgery, ideally within two weeks of event.
All patients undergoing carotid endarterectomy should receive optimal medical therapy
in addition to surgery.
;;
1++
A proportion of patients who are severely disabled immediately following their stroke event
can make rapid recovery such that they meet the criteria used in the studies (mRS2).
;;
11.1.2
Patients who are severely disabled immediately following their stroke event should
be considered for carotid endarterectomy if they recover sufficiently to meet the criteria
for surgery.
1++
43
Management of patients with stroke or TIA: assessment, investigation, immediate management and secondary prevention
Table 3 Number of patients with asymptomatic carotid artery disease needed to treat with CEA
to prevent an unfavourable outcome within three years249
Outcome
NNT
59
36
49*
*not significant
A
;;
B
11.1.3
CEA should be considered for asymptomatic patients with high grade carotid stenosis
and no ipsilateral event for at least six months.
CEA may be of more benefit for patients who:
are <70 years of age
are male
have bilateral disease.
CEA should only be performed by operators with a low (<3%) perioperative stroke or
death rate.
11.1.4
Patch angioplasty should be used as the closure method in all carotid endarterectomies
performed by conventional methods.
44
1+
1++
11 CAROTID INTERVENTION
A meta-analysis of seven RCTs (554 operations) and 41 non-randomised controlled trials (25,622
operations) found no reliable evidence to guide the choice between local or general anaesthesia
for patients undergoing carotid surgery.252
A
1+
The choice of anaesthetic technique for patients undergoing surgery should be made by
the individual operator/anaesthetist.
A systematic review found no data to support or refute the use of routine shunting over selective
shunting in CEA. 253
11.2
;;
Angioplasty and stenting may be considered for patients with high risk of stroke
recurrence and a hostile surgical neck (for example, previous radical neck dissection
or radiotherapy).
1++
1++
Antiplatelet treatment is described in section 5.2 and antiplatelet therapy to prevent recurrent
stroke is discussed in section 9.1.
A
45
Management of patients with stroke or TIA: assessment, investigation, immediate management and secondary prevention
Responsibility
Advice
patient receives suggestions that will help him or her in the change process
Menu
Empathy
Self efficacy
;;
12.2
Patients should be encouraged to take responsibility for their own health and be supported
to identify, prioritise, and manage their risk factors.
46
Diets low in total and saturated fats should be recommended to all for the reduction
of cardiovascular risk.
1++
12.2.2
omega-3 fats
There is conflicting evidence from two systematic reviews on the benefits associated with
increased consumption of omega-3 fats for the prevention of cardiovascular or stroke disease.257,258
It is not clear that dietary or supplemental omega-3 fats change total mortality, cardiovascular
events or cancer in people with, or at risk of, cardiovascular disease.257
For secondary prevention most trials reported that fish oil significantly reduced all-cause
mortality, MI, cardiac and sudden death, and stroke. Effects on stroke were inconsistent, and
the evidence suggests that increased consumption of omega-3 fats from fish or fish oil, but not
of -linolenic acid (ALA, found in certain vegetable oils, such as flax seed, soybean, walnuts,
canola) may be beneficial. The review also stated that five cohort studies provided no evidence
to support the hypothesis that fish consumption reduces the risk of stroke.258
In view of this uncertain effect and in order to avoid conflicting dietary advice, no change is
recommended in the current dietary guidelines (two 140 g portions of fish, one of which should
be a fatty fish, per week).259
;;
1++
All individuals should eat at least two portions of fish per week, one of which should be
a fatty fish.
No evidence was identified to advise people to stop taking supplemental omega-3 fats.
12.3
1+
A Cochrane review of advice to reduce salt intake lasting at least six months also reported small
but significant benefits to blood pressure. Long term maintenance of low sodium diets was
difficult for individuals, even with considerable advice, support and encouragement.261
1+
The Food Standards Agency has recommended that adults should consume no more than 6 g
of salt per day (approximately equivalent to one teaspoonful).262
A
;;
People with hypertension should be advised to reduce their salt intake as much as
possible to lower blood pressure.
All individuals should aim to consume less than 6 g of salt per day.
47
Management of patients with stroke or TIA: assessment, investigation, immediate management and secondary prevention
2++
Many observational studies of fruit consumption correlate with healthy behaviours and lifestyle in
general, for example smoking less, exercising more and having a higher level of education.
C
12.5
vitamin supplements
An association between hyperhomocysteinaemia and vascular disease including stroke has been
demonstrated in epidemiological studies.264 There is a twofold greater risk of stroke associated
with hyperhomocysteinaemia.
A trial of vitamin B12 and folate in patients with stroke found that lowering total homocysteine
by 2 mmol/L (027 mg/L) with high-dose B-multivitamin therapy did not prevent recurrent stroke
in patients with recent ischaemic stroke.265
1++
1+
12.6
weight reduction
One systematic review of RCTs of diet to reduce weight, which evaluated the effect on blood
pressure, was identified. Only small numbers of patients were included in the trials (six trials
including 361 participants).267 Dietary interventions to reduce weight were moderately effective
at reducing blood pressure. Diets producing weight loss in the range of 3% to 9% body weight
were partially associated with blood pressure reductions of about 3 mm Hg systolic and diastolic.
The review was underpowered to detect differences in morbidity or mortality outcomes.
B
12.7
Patients and individuals at risk of cardiovascular disease, who are overweight, should
be targeted with interventions designed to reduce weight, and to maintain this
reduction.
smoking
Tobacco smoking is strongly and dose-dependently associated with all cardiovascular events,
including coronary heart disease (CHD), stroke, peripheral arterial disease (PAD) and cardiovascular
death.268,269 Smoking cessation reduces these risks substantially, although the decrease is dependent
on the duration of cessation.270,271
B
All people who smoke should be advised to stop and offered support to help facilitate
this in order to minimise cardiovascular and general health risks.
12.8 alcohol
;;
48
1+
When giving advice to patients with stroke, the current general advice of no more than
two to three units of alcohol per day for women and no more than three to four units of
alcohol per day for men, with at least two drink-free days per week for both men and
women, should be recommended.272,273
2++
4
12.9
exercise
Physical activity is an important aspect of lifestyle that patients at risk of recurrent stroke can
modify.274 A meta-analysis of epidemiological data from large observational studies looking at
primary prevention (not stroke specific) indicated that physical activity may reduce the risk of
stroke.274 Increased occupational activity was associated with a lower risk of ischaemic stroke
compared to a moderate or inactive occupation. Overall moderate occupational activity gave a 15%
lower risk in total stroke compared to inactive people. The majority of these studies were carried
out at least six months, and in some cases up to 12 years post stroke and involved participants who
were ambulatory. It may be reasonable to extrapolate this information to secondary prevention.
2+
There may be many reasons why older people do not participate in physical activities.275
lack of interest
lack of access to a car
shortness of breath
joint pain
dislike of going out alone
perceived lack of fitness
lack of energy
doubting that exercise can lengthen life.
A systematic review of physical fitness training after stroke identified 12 trials (289 patients) with
an intervention to improve either muscle strength with or without cardiorespiratory fitness.276
Many of the trials had participants who volunteered and were ambulatory. Trial quality was
varied and outcome measures were very diverse. The benefits of physical fitness training
appeared to be short term only. Consequently, few conclusions can be drawn about the impact
of physical fitness training. A second systematic review of the same data showed no evidence
of effect rather than evidence of no effect.277 Individual studies showed an increase in quality
of life and reduction in the level of impairment. Secondary prevention was not an outcome but
positive effects from cardiovascular training on gait speed, stair climbing, human activity profile,
motor function, workload and exercise time were reported. A study comparing three 40 minute
sessions of treadmill training a week for six months with a programme of common components of
conventional rehabilitation showed that treadmill training was superior at improving cardiovascular
fitness.278 In a small study (13 participants) patients in a water-based programme of three one hour
sessions per week for eight weeks showed significant improvement in cardiovascular fitness over
the control group at least one year post stroke.279
1++
1+
An observational study of 25 patients one to 12 years post stroke taking part in an exercise group
demonstrated that improvement in balance and functional activity could be acquired well after
the initial stroke episode and improvement was retained at least one month after the programme
stopped.280 The benefits of physical exercise, in terms of function and quality of life, tend to be
lost after the formal programme of exercise stops.281,282
Nationally recognised recommendations state that all adults should accumulate 30 minutes
of moderate activity on most days of the week.283 National guidance is available on the most
effective way to promote physical activity.284,285
`B
49
Management of patients with stroke or TIA: assessment, investigation, immediate management and secondary prevention
13 Provision of information
This section reflects the issues likely to be of most concern to patients and their carers. These
points are provided for use by health professionals when discussing the acute phase of stroke with
patients and carers and in guiding the production of locally produced information materials.
1++
One study showed that younger patients required more medical information as well as having
questions concerning exercise and post-stroke sexual activities. Women ranked receiving
information on post-stroke management higher than men.287 Carers information requirements
also differ with age and sex.288 Female relatives place more importance on information. Relatives
with higher educational level place less importance on counselling.
In hospital 77% of patients and carers wanted information on preventing further strokes, 65%
on where to obtain further information, 65% on causes of stroke, 61% on risk factors for stroke,
60% on recovery, 54% on what a stroke is and 53% on stroke-related medications.289 Seventy
five per cent of carers wanted information on the emotional or psychological effects of stroke.289
At six months the most frequently desired topic by both patients and carers was prevention
of further strokes (67% of people surveyed), where to obtain more information (33%) and the
cognitive effects of stroke (33%).289
In one study patients were given a guide on discharge, which they could use as a reference
tool. Patients and carers suggested topics for the guide. The patients were all younger with few
disabilities and had healthy carers. The study showed that 59% of patients and caregivers wanted
to receive information once or twice, 22% three to six times or more frequently,19-59% would
like to receive information within 24 hours and 22% on day one to two weeks after the event.
The preferred information was medical information about the course of the disease, its cause,
consequences and treatment (see Table 5).290 At six months patients and carers still require
information and in a self reporting study some people may have forgotten between discharge
and six months that they had received information.289 A questionnaire of knowledge of stroke
showed that family members do not retain information offered concluding that information
should be given frequently.291
50
In one study 119 out of 252 patients responded to a questionnaire about the usefulness of a
patient-held record. Twenty seven per cent had lost it, only 59% read it and two thirds said that
they had difficulty in getting staff to record in it. Half of patients thought it was more trouble
than benefit.292
2+
Material given to patients and carers may not be suitable. One study showed that the readability
and accessibility of material was equivalent to 11th grade (UK equivalent of fourth year at
secondary school, age 15). The average ability of the carers was 9th grade (second year at
secondary school, age 13) and the patients 7-8th grade (primary 7-first year at secondary school,
age 11-12).289
13 PROVISION OF INFORMATION
Table 5 The five most important issues identified by patients and carers looking for
information290
Issue
Medical Information
Consequences of stroke
Experiences of other patients and caregivers
Home recovery
Advice for the partner and the social circle
D
Healthcare professionals should take a patients age, gender, educational status and
communication support needs into account when assessing their need for
information.
;;
Relatives needs are reported as information, counselling (communication and support) and
accessibility to staff.288 They often find the first three days of hospitalisation very emotional and
tiring. In this period most relatives focus on the patient and their illness rather than their own
needs.288 Carers may have to adapt to altered or additional roles (for example, driving) and their
relationship with the patient may change.293
Carers can feel that they lack knowledge and are unable to help or cope. They often require
information that they feel may not have been provided to them by staff. The carers burden is
lessened when they are able to care for the person with stroke in hospital.293,294
A systematic review of intervention studies for caregivers of people after a stroke studied four
types of support programmes targeted at caregivers problems and needs:
1++
Counselling programmes appeared to have most positive outcomes in terms of health related
quality of life, satisfaction, confidence and knowledge, problem solving skills, emotional state,
burden and caregiver preparedness. The aim of counselling was to teach caregivers coping
strategies to reduce stress. Counselling was more effective than education alone. Up to three
years after counselling confidence and knowledge about patient care and use of active coping
strategies were increased. Counselling is a time consuming intervention with around about
eight hours of individual counselling given. More research is required taking into account the
needs of caregivers.295
51
Management of patients with stroke or TIA: assessment, investigation, immediate management and secondary prevention
Training care givers in basic skills reduces the burden of care and improves quality of life for
patients and carers.296 Three to five 30-40 minute sessions of training defined by the needs of
the patient were effective. The type of training offered in the study is shown in Table 6. At three
and 12 months patients whose caregivers had received training reported significantly improved
quality of life and mood outcomes and burden of care was reduced and quality of life and
mood outcomes were improved in caregivers. The study was biased towards middle class, fit
participants and may not be applicable to all patients with stroke and their carers. There were
no data on which type of training was most useful. The study was in the rehabilitation setting
but the results may be extrapolated to the acute setting.
Table 6 Caregiver training provided by healthcare professionals296
Instruction on common stroke-related problems
positioning
prevention of bed sores
continence
nutrition
gait facilitation
advice on benefits and local services
Hands on training tailored to the needs of the patient
moving and handling
activities of daily living and communication
mobilisation
;;
Healthcare professionals should discuss the caring role and its implications with
relatives.
Healthcare professionals should actively involve carers and find out what support they
need.
;;
Carers should be given advice about where to seek support (for example, GP, voluntary
organisations, etc).
D
;;
13.2
52
1++
13 PROVISION OF INFORMATION
Connect
16-18 Marshalsea Road, London, SE1 1HL
Tel: 020 7367 0840
www.ukconnect.org
Works to promote effective services, new opportunities and a better quality of life for people
living with aphasia. Useful publications for people with aphasia and carers of people with
aphasia are available.
Different Strokes (Scotland)
53 Elmore Avenue, Glasgow, G44 5BH
Tel: 0141 569 3200
www.differentstrokes.co.uk Email: [email protected]
Helps stroke survivors of working age to optimise their recovery, take control of their own lives
and regain as much independence as possible by providing a national network of weekly exercise
classes, practical, easy to use information, newsletters, interactive website and StrokeLine
telephone service.
DIPEX. Personal experiences of health and illness
www.dipex.org/stroke
The High Blood Pressure Foundation
Department of Medical Sciences, Western General Hospital, Crewe Road South,
Edinburgh, EH4 2XU
Tel: 0131 332 9211
Speakability
1 Royal Street, London SE1 7LL
Helpline: 080 8808 9572
www.speakability.org.uk
Offers impartial information and support for people with aphasia and their carers through its
helpline, website and training courses, and distributes its own fact sheets, low-cost publications
and videos.
The Stroke Association
Links House, 15 Links Place, Edinburgh EH6 7EZ
Tel: 0131 555 7240 Fax: 0131 555 7259 National Stroke Helpline: 0845 30 33 100
www.stroke.org.uk Email: [email protected]
Funds research into prevention, treatment and better methods of rehabilitation, and helps
stroke patients and their families directly through its Rehabilitation and Support Services. It
also produces publications including patient leaflets, Stroke News (a quarterly magazine) and
information for health professionals.
strokeinfoplus
www.strokeinfoplus.scot.nhs.uk
Provides access to stroke patient leaflets, and information on stroke support groups, social
security benefits, medicines and treatment, and the evidence and clinical trials on which
treatment is based.
13.2.2
53
Management of patients with stroke or TIA: assessment, investigation, immediate management and secondary prevention
54
14.1
14.2
14.2.1
14.2.2
55
Management of patients with stroke or TIA: assessment, investigation, immediate management and secondary prevention
56
15.1.1
15.1.2
15.2
15.2.1
15.2.2
57
Management of patients with stroke or TIA: assessment, investigation, immediate management and secondary prevention
15.2.3
15.2.4
early surgical evacuation (for example, six hour time window) versus conservative
treatment
minimally invasive surgery including aspiration via burr hole or stereotaxy, with and without
instillation of thrombolytic drugs, versus medical therapy and/or craniotomy
standardised medical management of patients in both arms of future trials.
15.2.7
58
15.2.8
Carotid intervention
An RCT of surgical interventions, such as CEA in patients with carotid disease who are
asymptomatic for TIA/stroke and are scheduled for cardiac surgery.
15.2.9
Provision of information
What information patients and carers need, how patients and carers are given information
(verbal, written etc) and in what format (easy access etc).
15.3
59
Management of patients with stroke or TIA: assessment, investigation, immediate management and secondary prevention
60
Mr Peter Stonebridge
Mr Paul Teenan
Mrs Amanda Wong
The membership of the guideline development group was confirmed following consultation
with the member organisations of SIGN. All members of the guideline development group
made declarations of interest and further details of these are available on request from the
SIGN Executive.
Guideline development and literature review expertise, support and facilitation were provided
by the SIGN Executive.
16.2.1
Patient Involvement
In addition to the identification of relevant patient issues from a broad literature search, SIGN
involves patients and carers throughout the guideline development process in several ways.
SIGN recruits a minimum of two patient representatives to guideline development groups
by inviting nominations from the relevant umbrella, national and/or local patient focused
organisations in Scotland. Where organisations are unable to nominate, patient representatives
are sought via other means, for example, from consultation with health board public involvement
staff.
Further patient and public participation in guideline development was achieved by involving
patients, carers and voluntary organisation representatives at the National Open Meeting (see
section 16.3.1). Patient representatives were invited to take part in the peer review stage of
the guideline and specific guidance for lay reviewers was circulated. Members of the SIGN
patient network were also invited to comment on the draft guideline section on provision of
information.
16.2.2 acknowledgements
SIGN is grateful to the following former members of the guideline development group.
Dr Niall Campbell
Dr Judith Keighley
Ms Avril Kerr
Dr Hamish MacRitchie
Dr Ron MacWalter
Ms Claire Ritchie
61
Management of patients with stroke or TIA: assessment, investigation, immediate management and secondary prevention
16.3
62
ABBREVIATIONS
Abbreviations
ABCD/ABCD2
ACE
AF
atrial fibrillation
ALA
-linolenic acid
ARR
BI
Barthel index
BNF
BP
blood pressure
CABG
CaNS
CAS
CCB
CC
common carotid
CCA
CEA
carotid endarterectomy
CE-MRA
contrast-enhanced MRA
CHARISMA
CHD
CI
confidence interval
CPASS
CT
computerised tomography
CTA
CVT
DVT
DWI
EDV
ECG
electrocardiogram
ECST
ESPRIT
EVD
FAST
FASTER
FAM
FES
first-ever-in-a-lifetime stroke
63
Management of patients with stroke or TIA: assessment, investigation, immediate management and secondary prevention
64
FIM
FRAMES
GCS
GKI
glucose/potassium/insulin
GP
general practitioner
HR
hazard ratio
HTA
IA
intra-arterial
ICA
ICH
intracerebral haemorrhage
ICP
intracranial pressure
INR
iu
international units
IV
intravenous
IVH
intraventricular haemorrhage
LAA
LAMS
LAPSS
LDL
LMWH
MASS
MATCH
MCA
MCN
MERCI
MI
myocardial infarction
MRA
MRI
mRS
MTA
NASCET
NEED
NG
nasogastric
NICE
NIHSS
NNH
NNT
NPV
ABBREVIATIONS
OGTT
OR
odds ratio
PAD
PEG
percutaneous gastrostomy
PET
PFO
PICH
PPI
PPV
PROACT
PSV
PTE
pulmonary thromboembolism
QALY
RCT
ROSIER
r-proUK
recombinant pro-urokinase
RR
relative risk
RRR
rt-PA
SCMU
SMC
SPECT
SSS
STICH
SWI
TCD
transcranial Doppler
TCCS
TIA
UFH
unfractionated heparin
UK
urokinase
WHO
65
Management of patients with stroke or TIA: assessment, investigation, immediate management and secondary prevention
Annex 1
Key questions used to develop the guideline
MANAGEMENT OF SUSPECTED STROKE OR TIA
Key question
See guideline
section
3.1, 3.3.4
2. In patients with symptoms suggestive of acute stroke or TIA does the use
of a standard assessment scale/method/tool compared to a standard history
and examination, improve:
a. accuracy, sensitivity, specificity of diagnosis
b. speed of referral to specialist services
c. time to diagnosis and treatment?
Consider: ambulance service, accident and emergency, nursing, primary care
and general practice
3.2, 3.3.1
3. In patients with suspected stroke or TIA which form of hospital care
reduces death or dependency?
a. general ward vs home
b. stroke unit vs home
c. stroke unit vs general ward
d. stroke team vs general ward
e. acute stroke unit vs general ward
f. neurology unit vs general ward.
Consider: medical receiving units, acute medical units and high dependency
units
3.3.2
3.3.3
66
ANNEXES
See guideline
section
6. In patients with suspected stroke or TIA does the use of assessment tools
identify those at low risk of:
a. early stroke recurrence
b. significant dependency
c. requiring hyper acute treatment such as thrombolysis
d. cerebral haemorrhage?
Consider: ambulance service, Accident and Emergency, nursing, primary care
and general practice
4.1.1-4.1.3
7. In patients with likely acute stroke or TIA what is the evidence that brain
imaging (CT, MRI) results in change of management, is cost effectiveness
and reduces disability or death?
4.2.2
Consider: no imaging, early, late (<3, <6, <14, <48 hours, <1 week, >1
week
8. In patients with likely acute stroke or TIA what is the evidence that
brain imaging within 3, 6, 24, 48, >48 hours results in a change of
management, increased diagnostic accuracy in terms of differentiation
of infarct from haemorrhage (sensitivity and specificity for infarct AND
haemorrhage)?
4.2.3
4.2.4
67
Management of patients with stroke or TIA: assessment, investigation, immediate management and secondary prevention
12. In patients with carotid territory TIA or stroke and/or retinal event
(including amaurosis fugax, transient monocular blindness and retinal
artery occlusion) does carotid imaging improve accuracy of diagnosis for
carotid disease on the symptomatic side (sensitivity, specificity, accuracy,
NPV & PPV) for the following outcomes?
a. plaque burden
b. plaque composition
c. plaque morphology
d. stenosis degree
e. stenosis extent
f. tandem disease (ipsilateral at site other than carotid bifurcation/carotid
bulb/internal carotid origin).
Consider:
a. ultrasound (greyscale)
b. duplex/Doppler ultrasound
c. contrast-enhanced ultrasound
d. CT angiography
e. MR angiography
f. contrast-enhanced MR angiography
g. angiography/arteriography
h. rotational angiography/arteriography.
13. In patients scheduled for cardiac surgery and who are asymptomatic
for TIA/stroke which modality of carotid imaging is most effective for
improving the outcomes of recurrent stroke/dependency/death?
a. duplex ultrasound
b. CT angiography
c. MR angiography
d. contrast-enhanced MR angiography
e. angiography/arteriography
f. rotational angiography.
Consider:
4.3.2
68
a. trans-thoracic echo
b. trans-oesophageal echo (TOE, TEE)
c. contrast-enhanced echo
d. trans-cranial Doppler
e. cardiac CT
f. cardiac MRI.
4.4
ANNEXES
15. In patients with confirmed stroke or TIA which diagnostic tests change
4.5
management/treatment?
a. thrombophilia screen (anti-thrombin, protein C, protein S, APC
resistance, Factor V Leiden genotyping, prothrombin 20210
mutation)
b. auto-antibody screen
c. rheumatoid factor
d. anti-nuclear factor
e. ANCA
f. anti-DNA
g. anti-cardiolipin antibodies
h. lupus anticoagulant
i. genetic testing
j. coagulation screen
k. serum protein electrophoresis
l. immunoglobulin levels
m.homocysteine levels
n. syphilis serology
o. sickle cell screen.
TREATMENT OF ISCHAEMIC STROKE
Key question
See guideline
section
16. Which therapeutic interventions in acute ischaemic stroke patients reduce 5.1-5.7
death or dependence, compared with placebo/standard management?
a. thrombolysis (IV) vs placebo
b. thrombolysis (IA) vs IV thrombolysis or vs placebo
c. general (anterior circulation)
d. basilar artery occlusion
e. antiplatelet agents vs control/placebo
f. heparin (UF or LMWT): heparin vs control or UF vs LMWT
g. neuroprotectants vs placebo
h. r educing raised ICP (positioning, hyperventilation, mannitol,
hypertonic saline, glycerol vs control)
i. decompressive surgery
j. hemicraniectomy vs control
k. post fossa decompression vs control
l. post fossa decompression vs EVD
m.EVD vs control
n. mechanical reperfusion vs control
clot retrieval
transcranial Doppler plus thrombolysis vs thrombolysis only
microbubbles.
17. In patients with acute ischaemic stroke, does temporary withdrawal of
intervention reduce death or dependence?
Consider:
5.8
69
Management of patients with stroke or TIA: assessment, investigation, immediate management and secondary prevention
See guideline
section
6.1-6.4
18. Which interventions reduce death or dependence in patients with PICH
(primary intracerebral haemorrhage)?
a. haematoma evacuation, immediate vs delayed vs none
b. neuroprotective agents vs placebo
c. thrombolysis vs placebo
d. recombinant factor VIIa vs placebo
e. acute blood pressure lowering vs no blood pressure lowering
f. vitamin K or fresh frozen plasma or concentrated clotting factors vs
placebo
g. interventions to reduce raised intracranial pressure (mannitol etc vs
placebo.
OTHER CAUSES OF STROKE
Key question
See guideline
section
19. In patients with cerebral venous sinus thrombosis which interventions
reduce death or dependence vs control?
a. anticoagulation (warfarin or heparin) vs placebo
b. anticoagulation vs antiplatelet agents
c. antiplatelet agents vs placebo
d. thrombolysis vs above therapies.
7.1
7.2
70
Key question
See guideline
section
21. In patients with acute stroke does the intensity (more vs less) of
physiological monitoring (heart rate, blood pressure, temperature, oxygen
saturation) in conjunction with a management protocol reduce death and
dependence?
a. blood glucose
b. blood pressure
c. temperature
d. oxygen saturation.
8.1
ANNEXES
22. In patients with acute stroke, which interventions vs control reduces death 8.2
or dependence?
a. intravenous fluids
- IV fluids vs oral fluids
- saline vs other (dextrose, Ringers, Hartmanns)
- high vs standard volume (>2 litres/24 hours vs <2 litres/24
hours)
b. blood pressure management
- active lowering vs control
- active elevating (sympathomimetic agents or plasma expanders
vs control)
- withdrawing antihypertensive drugs vs continuing
c. lowering blood glucose (insulin vs control)
d. f eeding (early vs deferred feeding, NG, PEG, supplementary
feeding)
e. s upplementary oxygen therapy vs standard, normobaric vs
hyperbaric
f. management of pyrexia (antipyretics vs control)
g. early mobilisation
h. active positioning
i. induction of hypothermia vs control.
71
Management of patients with stroke or TIA: assessment, investigation, immediate management and secondary prevention
See guideline
section
23. In patients with ischaemic stroke (or TIA) which therapies are proven to
9.1-9.5, 11.1,
reduce the incidence of recurrent stroke or cardiovascular events (non12.2.5
fatal MI, vascular death, non-fatal recurrent stroke)?
a. antiplatelet agents
- aspirin vs placebo, vs others in list, high dose>300mg vs low
dose (<300mg ), immediate vs deferred), aspirin vs aspirin plus
dipyridamole
- clopidogrel vs placebo, vs aspirin, vs aspirin plus clopidogrel, vs
dipyridamole plus aspirin
- dipyridamole vs placebo, vs aspirin, vs aspirin plus dipyridamole,
standard vs modified release
- triflusal vs aspirin
- combinations of these.
b. statins
- statins vs placebo
- statin vs statin (different drugs)
- statin vs other lipid-lowering interventions (fibrates, ezetemibe,
nicotinamide, cholestyramine, surgical)
- immediate vs delayed statin therapy.
- statin treatment to cholesterol target vs treatment irrespective of
cholesterol level.
c. anticoagulation
- in patients in AF. Warfarin vs placebo, warfarin vs aspirin or
clopidogrel/aspirin, or warfarin plus aspirin. Immediate vs
delayed.
- which INR?
- other stroke aetiologies (warfarin vs placebo, warfarin vs aspirin,
warfarin vs clopidogrel or combinations)
d. antihypertensives
- specific agents vs placebo
- specific agents vs each other, and also combinations.
- immediate v deferred treatment
- blood pressure target vs treatment irrespective of blood pressure
e. vitamins, minerals, dietary supplements/nutraceuticals vs placebo
f. carotid endarterectomy
g. atrial appendage occlusion.
24. In patients with patent foramen ovale and cryptogenic stroke, which
interventions reduce recurrent stroke or cardiovascular events?
a. antiplatelet vs warfarin
b. closure vs medical therapy (antiplatelets or warfarin).
72
9.7
ANNEXES
See guideline
section
25. In patients with PICH what interventions prevent recurrent vascular events
(recurrent stroke or cardiovascular events (non-fatal MI, vascular death,
non-fatal recurrent stroke)?
a. blood pressure reduction
b. antiplatelet agents
c. anticoagulation
d. statins.
10.1-10.4
26. In patients with haemorrhagic transformation of an ischaemic infarction does withdrawal
of antiplatelet agent (aspirin/clopidogrel/dipyridamole) or anticoagulant (warfarin, heparin)
affect death or disability?
CAROTID INTERVENTION
Key question
See guideline
section
27. In patients with carotid territory TIA or stroke and/or retinal event
(including amaurosis fugax, transient monocular blindness and retinal
artery occlusion) does carotid intervention reduce recurrent stroke/
dependency/death?
a. surgical carotid endarterectomy
b. carotid angioplasty and stent
c. carotid angioplasty and stent with cerebral protection.
11.1.1, 11.2
28. Patients with carotid disease who are asymptomatic in that (ipsilateral)
carotid territory does carotid intervention reduce recurrent stroke/
dependency/death?
a. surgical carotid endarterectomy
b. carotid angioplasty and stent
c. carotid angioplasty and stent with cerebral protection.
11.1.2, 11.2
29. In patients scheduled for cardiac surgery with carotid disease and who are 11.1.3
asymptomatic for TIA/stroke which carotid intervention reduces recurrent
stroke/dependency/death?
a. surgical carotid endarterectomy
b. carotid angioplasty and stent
c. carotid angioplasty and stent with cerebral protection.
Consider:
a. coronary artery bypass grafting (CABG)
b.valve replacement (aortic and/or mitral valves, with/without CABG)
c. left ventricular aneurysmectomy (with/without CABG)
d. thoracic aortic aneurysm repair.
30. In patients undergoing surgical carotid endarterectomy which carotid
surgery techniques reduces recurrent stroke/dependency/death?
a. local versus general anaesthetic
b. shunt or no shunt
c. patch or no patch
d. monitor with transcranial Doppler vs none
e. monitor with EEG vs none
f. monitor with infra-red spectroscopy vs none.
11.1.4
73
Management of patients with stroke or TIA: assessment, investigation, immediate management and secondary prevention
11.3
32. In patients presenting with stroke, TIA, crescendo TIA or stuttering
stroke and/or retinal events (amaurosis fugax, transient monocular
blindness and retinal artery occlusion) and carotid disease suitable for
intervention does early intervention reduce recurrent stroke/dependency/
death compared to delayed intervention or late intervention?
PROVISION OF INFORMATION
Key question
See guideline
section
33. What evidence is there for when and how patients with suspected stroke/
TIA and carers should be offered information?
12.1.1
12.1.1
12.1.1
36. What practical information can be given to carers about the day-to-day
living of a patient with acute stroke?
12.1.2
Consider: clothing, food and drink, eating, texture, dysphagia, impact of stroke
on lifestyle, mood, personality.
37. What early and ongoing support do carers need to help them cope with
caring for a patient with stroke?
12.1.2
12.2.1
74
12.2.2-12.2.8
ANNEXES
40. What are the best ways of motivating people to continue exercising after
discharge and are there any exercise programmes that link physiotherapist
led exercise and gym?
12.2.9
75
Management of patients with stroke or TIA: assessment, investigation, immediate management and secondary prevention
Annex 2
NIH stroke scale
The NIH stroke scale (NIHSS) is a 15-item neurologic examination stroke scale used to evaluate
the effect of acute cerebral infarction on the levels of consciousness, language, neglect, visualfield loss, extra-ocular movement, motor strength, ataxia, dysarthria, and sensory loss. A trained
observer rates the patents ability to answer questions and perform activities. Ratings for each
item are scored with 3 to 5 grades with 0 as normal, and there is an allowance for untestable
items. The single patient assessment requires less than 10 minutes to complete.
A free educational website presented by the International Electronic Education Network
provides tutorials, assessment and accreditation on the use of the NIHSS. The target audiences
for this programme are first responders, physicians, neurologists, nurses, clinical raters and
medical students (www.nihstrokescale.org).
76
ANNEXES
Annex 2 (continued)
77
Management of patients with stroke or TIA: assessment, investigation, immediate management and secondary prevention
Annex 2 (continued)
78
ANNEXES
Annex 2 (continued)
79
Management of patients with stroke or TIA: assessment, investigation, immediate management and secondary prevention
Annex 2 (continued)
80
ANNEXES
Annex 2 (continued)
81
Management of patients with stroke or TIA: assessment, investigation, immediate management and secondary prevention
Annex 2 (continued)
82
ANNEXES
Annex 2 (continued)
83
Management of patients with stroke or TIA: assessment, investigation, immediate management and secondary prevention
Annex 2 (continued)
84
ANNEXES
Annex 2 (continued)
85
Management of patients with stroke or TIA: assessment, investigation, immediate management and secondary prevention
Annex 3
Modified Rankin score298
A record of the functional outcome after an event based upon the extent of any disability
or disabling symptoms experienced by the patient following the event, measured using the
modified Rankin score (mRS) tool.
86
Score
Symptoms
Description
No symptoms
No significant disabling
symptoms
Slight disability
Moderate disability
Moderate/severe disability
Severe disability
Dead
Score of 6
ANNEXES
Annex 4
Face arm speech test (FAST) and instructions
Adapted from Harbison et al and reproduced by kind permission of Lippincott, Williams and
Wilkins, Baltimore18
STROKE (FACE ARM SPEECH TEST)
SPEECH IMPAIRMENT YES
NO
NO
AFFECTED SIDE L
NO
AFFECTED SIDE L
FACIAL MOVEMENTS
Ask patient to smile or show teeth
- Look for NEW lack of symmetry - Tick the YES box if there is an unequal smile or
grimace or obvious facial asymmetry
- Note which side does not move well, and mark on the form whether it is the
patient's right or left side
ARM MOVEMENTS
- Lift the patient's arms together to 90 if sitting, 45 if supine and ask them to hold the
position for 5 seconds then let go
- Does one arm drift down or fall rapidly?
- If one arm drifts down or falls, note whether it is the patient's left or right arm
SPEECH
If the patient attempts a conversation
- Look for NEW disturbance of speech
- Check with companion
- Look for slurred speech
- Look for word-finding difficulties. This can be confirmed by asking the patient to
name commonplace objects that may be nearby, such as a cup, chair, table
keys, pen
- If there is a severe visual disturbance, place an object in the patient's hand and ask
him/her to name it
87
Management of patients with stroke or TIA: assessment, investigation, immediate management and secondary prevention
Annex 5
MASS Test
Adapted from Bray et al and reproduced by kind permission of S. Karger AG, Basel.22
Assessment
History items
Age>45 years
Absent history of seizure or epilepsy
At baseline not wheelchair bound or bedridden
Blood glucose level between 2.8 and 22.2 mmol/L
Physical assessment items (normal and abnormal outcomes)
Facial droop
Patient smiles or shows teeth
(both sides move equally, one side does not move)
Arm drift
Patient closes eyes and extends both arms out for 10 seconds
(both arms move/both arms do not move, one arm does not move/one arm drifts
compared to the other)
Hand grip
Place a hand in each hand of the patient and ask him/her to squeeze hands
(both grip equally/not at all, unilateral weak/no grip)
Speech
Repeats a sentence
(normal, slurred/incorrect words, unable to speak)
88
ANNEXES
Annex 6
ROSIER scale proforma
Reprinted from Lancet Neurology, 4 (11), Azlisham Mohd Nor, John Davis, Bas Sen, Dean
Shipsey, Stephen J Louw, Alexander G Dyker, Michelle Davis, Gary A Ford. The Recognition
of Stroke in the Emergency Room (ROSIER) scale: development and validation of a stroke
recognition instrument, 72734, Copyright (2005), with permission from Elsevier.20
ASSESSMENT
Date
Time
SYMPTOM ONSET
Date
Time
GCS
E= M=
V=
BP
*BM
*If BM<3.5mmol/L treat urgently and reassess once blood glucose normal
Has there been loss of consciousness or syncope? Y (1)
N (0)
Y (1)
N (0)
N (0)
II.
N (0)
III.
N (0)
IV.
N (0)
V.
N (0)
*Total Score________(2 to + 5)
Provisional diagnosis
Stroke
Non-stroke (specify)_______________________________
89
Management of patients with stroke or TIA: assessment, investigation, immediate management and secondary prevention
Annex 7
ABCD/ABCD2
Reprinted from The Lancet, 366 (9479), Rothwell PM, Giles MF, Flossmann E, Lovelock CE,
Redgrave JN, Warlow CP, Mehta Z. A, A simple score (ABCD) to identify individuals at high
early risk of stroke after transient ischaemic attack, 29-36, Copyright (2005), with permission
from Elsevier.34, 299
Risk factor
Category
Score
Age of patient
Age60
Age<60
1
0
Blood pressure at
assessment
1
0
Clinical features
at presentation
Unilateral weakness
Speech disturbance (no weakness)
Other
2
1
0
Duration of TIA
symptoms
60 minutes
10-59 minutes
<10 minutes
2
1
0
Diabetes
1
TOTAL
90
/7
ANNEXES
Annex 8
Brain imaging for stroke
The choice of imaging of the brain in the acute phase of stroke is between CT and MRI (see
section 4.2.3). It is difficult to recommend which modality to use exclusively, as this will depend
upon individual patient circumstances. The strengths and weaknesses of both modalities are
shown in the table below to help inform choice. For the purposes of this table CT brain imaging
is unenhanced (without contrast) and MRI while also unenhanced is assumed to include diffusion
weighted imaging (DWI) and some form of susceptibility weighted imaging (SWI) sequences.
CT
MRI
Geographic availability
Increasing availability in
Scotland but still mainly
confined to the larger centres.
Out-of-hours availability
Sensitivity for
haemorrhage
The high sensitivity of CT for haemorrhage, its rapid acquisition and applicability in unwell
patients allows diagnostic decision making in many of those presenting with acute stroke
syndrome, especially where a substantial territory of brain is likely to be involved. For patients
presenting at later time points (days) MRI has advantage in differentiating haemorrhage from
ischaemia. Patients presenting with limited or unusual neurology (NIHSS 3), especially
brainstem syndromes, may also be better served by MRI as the first imaging investigation.
MRI is also useful after initial negative CT scan, where there is diagnostic doubt or the
definitive depiction of ischaemic damage will aid future management.
91
Management of patients with stroke or TIA: assessment, investigation, immediate management and secondary prevention
Annex 9
Carotid stenosis
A misconception engendered by the concentration on stenosis measurement is that stenosis
causes stroke when in fact it is not stenosis in itself (luminal narrowing impeding blood flow)
that is the main cause of stroke, rather in the context of carotid disease stroke is usually caused
by atheroembolism. At the time of the North American Symptomatic Carotid Endarterectomy
Trial (NASCET) the only imaging methodology available to visualise carotid atheromatous disease
burden was conventional selective carotid angiography using cut film. The sole means by which
these images could be analysed for disease quantification was to measure stenosis. In NASCET
the stenosis was measured with the luminal diameter of the normal appearing internal carotid
artery distal to the site of stenosis as the denominator. A potential limitation of this is that at
higher grades of narrowing when the normal vessel beyond a stenosis becomes depressurised
this intrinsically affects the calculation. As a small vessel the potential errors in measurement
of the internal carotid are relatively greater than in a larger artery such as the common carotid.
The European Carotid Surgery Trial also used angiographic measurement but did not demand
selective arteriograms and used a different method for stenosis calculation using the perceived
normal diameter of the vessel at the site of disease (usually the carotid bulb) as the denominator.
This normal diameter is not actually delineated on arteriography and it is likely that this
measurement was judged by extrapolation of the common carotid artery diameter proximal to
the disease. It has been proposed that the denominator should be the common carotid artery,
unaffected by post-stenotic pressure phenomena and better inter-observer diameter estimation,
however, the NASCET criterion has become the accepted standard.
The figure below shows a comparison of the methods used to measure carotid stenosis as assessed
by diameter reduction shown on angiography. There is also a diagrammatic representation
of ulcerated plaque for which simple stenosis assessment would underestimate the degree of
pathology and potential for atheroembolism.
Picture of bifurcation with different denominators illustrated
A
C
92
ANNEXES
Annex 10
Carotid Duplex Reporting
The degree of internal carotid artery stenosis as found with carotid duplex ultrasound should
be reported in broad categories. Attempts to grade carotid stenosis to more precise degrees by
ultrasound are inappropriate. The grade of stenosis reported should be based on a combination
of parameters and not just one variable. The report should state the velocity measurements
and also the gray-scale and colour Doppler findings. A degree of stenosis >50% should be
corroborated by a second imaging modality.300
Degree of stenosis ICA PSV
(%)
(cm/sec)
Plaque estimate
(%)
ICA/CCA PSV
ratio
ICA EDV
(cm/sec)
Normal
<125
None
<2.0
<40
<50
>125
<50
<2.0
<40
50-69
125-230
50
2.0-4.0
40-100
>230
50
>4.0
>100
Near occlusion
High, low or
undetectable
Visible
Variable
Variable
Total occlusion
Undetectable
Visible, no
detectable lumen
Not applicable
Not
applicable
ICA internal carotid artery, PSV peak systolic velocity, CCA common carotid artery
EDV end diastolic velocity
Reprinted from Grant EG, Benson CB, Moneta GL, et al. Carotid artery stenosis: gray-scale
and Doppler US diagnosis-society of radiologists in ultrasound consensus conference.
Radiology 2003;229:340-346 with permission from The Radiological Society of North
America (RSNA)300
93
Management of patients with stroke or TIA: assessment, investigation, immediate management and secondary prevention
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