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Long-term management and secondary prevention

5.0 Introduction

From the moment a person has a stroke or TIA they are at substantial increased risk of further events; 26% within 5 years of a first stroke and 39% by 10 years (Mohan et al, 2011)....

5.1 A comprehensive and personalised approach

Ensuring the identification and modification of all risk factors, including lifestyle issues, should lead to more effective secondary prevention of stroke and other vascular events...

Recommendations
A

People with stroke or TIA should receive a comprehensive and personalised strategy for vascular prevention including medication and lifestyle factors, which should be implemented as soon as possible and should continue long-term. [2016]

B

People with stroke or TIA should receive information, advice and treatment for stroke, TIA and vascular risk factors which is:

  • given first in the hospital or clinic setting;
  • reinforced by all health professionals involved in their care;
  • provided in an appropriate format. [2016]
C

People with stroke or TIA should have their risk factors and secondary prevention reviewed and monitored at least once a year in primary care. [2016]

D

People with stroke or TIA who are receiving medication for secondary prevention should:

  • receive information about the reason for the medication, how and when to take it and common side effects;
  • receive verbal and written information about their medicines in an appropriate format;
  • be offered compliance aids such as large-print labels, non-childproof tops and dosette boxes according to their level of manual dexterity, cognitive impairment, personal preference and compatibility with safety in the home;
  • be aware of how to obtain further supplies of medication;
  • have their medication regularly reviewed;
  • have their capacity to take full responsibility for self-medication assessed (including cognition, manual dexterity and ability to swallow) by the multidisciplinary team as part of their rehabilitation prior to the transfer of their care out of hospital. [2016]
Sources, evidence to recommendations, implications

5.2 Identifying risk factors

The risk of recurrent vascular events may vary significantly between individuals according to underlying pathology, co-morbidities and lifestyle factors.  This guideline applies to...

Recommendations
A

People with stroke or TIA for whom secondary prevention is appropriate should be investigated for risk factors as soon as possible within 1 week of onset. [2016]

B

Provided they are eligible for any resultant intervention, people with stroke or TIA should be investigated for the following risk factors:

  • ipsilateral carotid artery stenosis;
  • atrial fibrillation;
  • structural cardiac disease. [2016]
C

People with evidence of non-symptomatic cerebral infarction on brain imaging (silent cerebral ischaemia) should have an individualised assessment of their vascular risk and secondary prevention. [2016]

Sources, evidence to recommendations, implications

5.3 Carotid artery stenosis

Atheroma and stenosis of the carotid arteries is commonly associated with stroke and TIA, and surgical or radiological interventions (endarterectomy or stenting) have been used to

...

Recommendations
A

Following stroke or TIA, the degree of carotid artery stenosis should be reported using the North American Symptomatic Carotid Endarterectomy Trial (NASCET) method. [2016]

B

People with non-disabling carotid artery territory stroke or TIA should be considered for carotid revascularisation, and if they agree with intervention:

  • they should have carotid imaging (duplex ultrasound, MR or CT angiography) performed urgently to assess the degree of stenosis;
  • if the initial test identifies a relevant severe stenosis (greater than or equal to 50%), a second or repeat non-invasive imaging investigation should be performed to confirm the degree of stenosis. This confirmatory test should be carried out urgently to avoid delaying any intervention. [2016]
C

People with non-disabling carotid artery territory stroke or TIA should be considered for carotid revascularisation if the symptomatic internal carotid artery has a stenosis of greater than or equal to 50%.  The decision to offer carotid revascularisation should be:

  • based on individualised risk estimates taking account of factors such as the time from the event, gender, age and the type of qualifying event;
  • supported by risk tables or web-based risk calculators (e.g. the Oxford University Stroke Prevention Research Unit calculator, https://www.ndcn.ox.ac.uk/divisions/cpsd/carotid-stenosis-tool-1). [2016]
D

People with non-disabling carotid artery territory stroke or TIA and a carotid stenosis of less than 50% should not be offered revascularisation of the carotid artery. [2016]

E

Carotid endarterectomy for people with symptomatic carotid stenosis should be:

  • the treatment of choice, particularly for people who are 70 years of age and over or for whom the intervention is planned within seven days of stroke or TIA;
  • performed in people who are neurologically stable and who are fit for surgery using either local or general anaesthetic according to the person’s preference;
  • performed as soon as possible and within 1 week of first presentation;
  • deferred for 72 hours in people treated with intravenous thrombolysis;
  • only undertaken by a specialist surgeon in a vascular centre where the outcomes of carotid surgery are routinely audited. [2016]
F

Carotid angioplasty and stenting should be considered for people with symptomatic carotid stenosis who are:

  • unsuitable for open surgery (e.g. high carotid bifurcation, symptomatic re-stenosis following endarterectomy, radiotherapy-associated carotid stenosis);

or

  • less than 70 years of age and who have a preference for carotid artery stenting.

The procedure should only be undertaken by an experienced operator in a vascular centre where the outcomes of carotid stenting are routinely audited. [2016]

G

People who have undergone carotid revascularisation should be reviewed post-operatively by a stroke physician to optimise medical aspects of vascular secondary prevention. [2016]

H

Patients with atrial fibrillation and symptomatic internal carotid artery stenosis should be managed for both conditions unless there are contraindications. [2016]

Sources, evidence to recommendations, implications

5.4 Blood pressure

Blood pressure (BP) is the pre-eminent treatable risk factor for first and recurrent stroke. It is estimated to cause about 50% of ischaemic strokes and is the principal risk facto...

Recommendations
A

People with stroke or TIA should have their blood pressure checked, and treatment should be initiated or increased as tolerated to consistently achieve a clinic systolic blood pressure below 130 mmHg, equivalent to a home systolic blood pressure below 125 mmHg. The exception is for people with severe bilateral carotid artery stenosis, for whom a systolic blood pressure target of 140–150 mmHg is appropriate.  Concern about potential adverse effects should not impede the initiation of treatment that prevents stroke, major cardiovascular events or mortality. [2023]

B

For people with stroke or TIA aged 55 or over, or of African or Caribbean origin at any age, antihypertensive treatment should be initiated with a long-acting dihydropyridine calcium-channel blocker or a thiazide-like diuretic.  If target blood pressure is not achieved, an angiotensin converting enzyme inhibitor or angiotensin II receptor blocker should be added. [2016]

C

For people with stroke or TIA not of African or Caribbean origin and younger than 55 years, antihypertensive treatment should be initiated with an angiotensin converting enzyme inhibitor or an angiotensin II receptor blocker. [2016]

D

People with stroke or TIA should have blood pressure-lowering treatment initiated prior to the transfer of care out of hospital or at 2 weeks, whichever is the soonest, or at the first clinic visit for people not admitted. [2016]

E

People with stroke or TIA should have their blood pressure-lowering treatment monitored frequently in primary care and increased to achieve target blood pressure as quickly and safely as tolerated.  People whose blood pressure remains above target despite treatment should be checked for medication adherence at each visit before escalation of treatment, and people who do not achieve their target blood pressure despite escalated treatment should be referred for a specialist opinion.  Once blood pressure is controlled to target, people taking antihypertensive treatment should be reviewed at least annually. [2023]

F

In people with stroke being treated with antihypertensive agents to reduce recurrent stroke risk, management guided by home or ambulatory BP monitoring should be considered, in order to improve treatment compliance and BP control. [2023]

G

People with stroke using home BP monitoring should use a validated device with an appropriate measurement cuff and a standardised method.  They (or where appropriate, their family/carer) should receive education on how to use the device, the implications of readings for management, and be provided with ongoing support, particularly if they have anxiety or cognitive and physical disability after stroke. [2023]

Sources, evidence to recommendations, implications

5.5 Lipid modification

Raised lipid levels, especially hypercholesterolaemia, are an important modifiable risk factor for cardiovascular events, especially myocardial infarction.  Lipid-lowering treatmen...

Recommendations
A

People with ischaemic stroke or TIA should be offered personalised advice and support on lifestyle factors to reduce cardiovascular risk, including diet, physical activity, weight reduction, alcohol moderation and smoking cessation. [2023]

B

People with ischaemic stroke or TIA should be offered treatment with a statin unless contraindicated or investigation of their stroke or TIA confirms no evidence of atherosclerosis.  Treatment should:

  • begin with a high-intensity statin such as atorvastatin 80 mg daily. A lower dose should be used if there is the potential for medication interactions or a high risk of adverse effects;
  • be with an alternative statin at the maximum tolerated dose if a high-intensity statin is unsuitable or not tolerated. [2023]
C

Lipid-lowering treatment for people with ischaemic stroke or TIA and evidence of atherosclerosis should aim to reduce fasting LDL-cholesterol to below 1.8 mmol/L (equivalent to a non-HDL-cholesterol of below 2.5 mmol/L in a non-fasting sample).  If this is not achieved at first review at 4-6 weeks, the prescriber should:

  • discuss adherence and tolerability;
  • optimise dietary and lifestyle measures through personalised advice and support;
  • consider increasing to a higher dose of statin if this was not prescribed from the outset;
  • consider adding ezetimibe 10 mg daily;
  • consider the use of additional agents such as injectables (inclisiran or monoclonal antibodies to PCSK9) or bempedoic acid (for statin-intolerant people taking ezetimibe monotherapy);
  • continue to escalate lipid-lowering therapy (in combination if necessary) at regular intervals in order to reduce LDL-cholesterol to below 1.8 mmol/L. [2023]
D

People with ischaemic stroke or TIA in whom investigation confirms no evidence of atherosclerosis should be assessed for lipid-lowering therapy on the basis of their overall cardiovascular risk. [2023]

E

People with intracerebral haemorrhage should be assessed for lipid-lowering therapy on the basis of their overall cardiovascular risk and the underlying cause of the haemorrhage. [2023]

F

In people with ischaemic stroke or TIA below 60 years of age with very high cholesterol (below 30 years with total cholesterol above 7.5 mmol/L or 30 years or older with total cholesterol concentration above 9.0 mmol/L) consider a diagnosis of familial hypercholesterolaemia. [2023]

G

In people with ischaemic stroke or TIA of presumed atherosclerotic cause below 60 years of age, consider the measurement of lipoprotein(a) and specialist referral if raised above 200 nmol/L. [2023]

Sources, evidence to recommendations, implications

5.6 Antiplatelet treatment

Antiplatelet treatment is one of the most important interventions for reducing the risk of recurrent vascular events including stroke.  Most long-term evidence relates to aspirin, ...

Recommendations
A

For long-term prevention of vascular events in people with ischaemic stroke or TIA without paroxysmal or permanent atrial fibrillation:

  • clopidogrel 75 mg daily should be the standard antithrombotic treatment;
  • aspirin 75 mg daily should be used for those who are unable to tolerate clopidogrel;

if a patient has a recurrent cardiovascular event on clopidogrel, clopidogrel resistance may be considered.

The combination of aspirin and clopidogrel is not recommended for long-term prevention of vascular events unless there is another indication e.g. acute coronary syndrome, recent coronary stent. [2023]

B

People with ischaemic stroke with acute haemorrhagic transformation should be treated with long-term antiplatelet or anticoagulant therapy unless the prescriber considers that the risks outweigh the benefits. [2023]

C

Patients who have a spontaneous (non-traumatic) intracerebral haemorrhage (ICH) whilst taking an antithrombotic (antiplatelet or anticoagulant) medication for the prevention of occlusive vascular events may be considered for restarting antiplatelet treatment beyond 24 hours after ICH symptom onset. [2023]

D

Clinicians should consider the baseline risks of recurrent ICH and occlusive vascular events when making a decision about antiplatelet use after ICH outside randomised controlled trials. [2023]

E

Wherever possible, patients with spontaneous (non-traumatic) ICH and a co-existent indication for antithrombotic medication treatment should be encouraged to participate in randomised controlled trials of antithrombotic therapy. [2023]

Sources, evidence to recommendations, implications

5.7 Anticoagulation

Treatment with anticoagulation after TIA or ischaemic stroke is now usually restricted to long-term secondary prevention of cardioembolic stroke due to atrial fibrillation (AF), in...

Recommendations
A

For people with ischaemic stroke or TIA and paroxysmal, persistent or permanent atrial fibrillation (AF: valvular or non-valvular) or atrial flutter, oral anticoagulation should be the standard long-term treatment for stroke prevention.  Anticoagulant treatment:

  • should not be given if brain imaging has identified significant haemorrhage;
  • should not be commenced in people with severe hypertension (clinic blood pressure of 180/120 or higher), which should be treated first;
  • may be considered for patients with moderate-to-severe stroke from 5-14 days after onset. Wherever possible these patients should be offered participation in a trial of the timing of initiation of anticoagulation after stroke.  Aspirin 300 mg daily should be used in the meantime;
  • should be considered for patients with mild stroke earlier than 5 days if the prescriber considers the benefits to outweigh the risk of early intracranial haemorrhage. Aspirin 300 mg daily should be used in the meantime;
  • should be initiated within 14 days of onset of stroke in all those considered appropriate for secondary prevention;
  • should be initiated immediately after a TIA once brain imaging has excluded haemorrhage, using an agent with a rapid onset (e.g. DOAC in non-valvular AF or subcutaneous low molecular weight heparin while initiating a VKA for those with valvular AF);
  • should include measures to reduce bleeding risk, using a validated tool to identify modifiable risk factors. [2023]
B

First-line treatment for people with ischaemic stroke or TIA due to non valvular AF should be anticoagulation with a DOAC. [2023]

C

People with ischaemic stroke or TIA in sinus rhythm should not receive anticoagulation unless there is another indication. [2023]

D

People with ischaemic stroke or TIA due to valvular/rheumatic AF or with mechanical heart valve replacement, and those with contraindications or intolerance to DOAC treatment, should receive anticoagulation with adjusted-dose warfarin (target INR 2.5, range 2.0 to 3.0) with a target time in the therapeutic range of greater than 72%. [2023]

E

For people with cardioembolic TIA or stroke for whom treatment with anticoagulation is considered inappropriate because of a high risk of bleeding:

  • antiplatelet treatment should not be used as an alternative when there are absolute contraindications to anticoagulation (e.g. undiagnosed bleeding);
  • measures should be taken to reduce bleeding risk, using a validated tool to identify modifiable risk factors. If after intervention for relevant risk factors the bleeding risk is considered too high for anticoagulation, antiplatelet treatment should not be routinely used as an alternative;
  • a left atrial appendage occlusion device may be considered as an alternative, provided the short-term peri-procedural use of antiplatelet therapy is an acceptable risk. [2023]
F

People with cardioembolic TIA or stroke for whom treatment with anticoagulation is considered inappropriate for reasons other than the risk of bleeding may be considered for antiplatelet treatment to reduce the risk of recurrent vaso-occlusive disease. [2023]

G

People who initially present with recurrent TIA or stroke should receive the same antithrombotic treatment as those who have had a single event.  More intensive antiplatelet therapy or anticoagulation treatment should only be given as part of a clinical trial or in exceptional clinical circumstances. [2023]

Sources, evidence to recommendations, implications
Sources
A

EAFT Study Group, 1993; Miller et al, 2012; Paciaroni et al, 2015; Gioia et al, 2016; Klijn et al, 2019; Hindricks et al, 2020; Labovitz et al, 2021; Steffel et al, 2021; De Marchis et al, 2022; Guideline Development Group consensus

B

Guideline Development Group consensus

C

De Schryver et al, 2012; Guideline Development Group consensus

D

EAFT Study Group, 1993; Miller et al, 2012; Eikelboom et al, 2013; Ruff et al, 2014; Graham et al, 2015; Makam et al, 2018; Hirschl and Kundi, 2019; Hindricks et al, 2020; Shen et al, 2020; Steffel et al, 2021; Xu et al, 2021; Connolly et al, 2022

E

Reddy et al, 2013; NICE, 2021a; Guideline Development Group consensus

F

Benz et al, 2022

G

Guideline Development Group consensus

Evidence to recommendations

Anticoagulant treatment is not more effective than antiplatelet therapy in people with non-cardioembolic ischaemic stroke or TIA and carries a greater risk of bleeding (Mohr et al, 2001; Sandercock et al, 2009). Neither is there evidence of greater efficacy for anticoagulation in embolic stroke of uncertain source (ESUS; Hart et al, 2018; Diener et al, 2019). A Cochrane review found no evidence that early initiation of anticoagulation (within 2 weeks) in unselected patients with (all cause) ischaemic stroke reduced death or disability at or beyond 1 month. There was moderate grade evidence of large reductions in recurrent ischaemic stroke and pulmonary embolism with moderate increased rates of intracranial and extracranial bleeding (Wang et al, 2021b). [2023]

Intracranial haemorrhage (including haemorrhagic transformation of the acute infarct) should be assessed by brain imaging and taken into account when deciding whether and when to commence anticoagulation. Less severe degrees of haemorrhagic transformation may not necessarily be a contraindication to anticoagulation, an issue that will be clarified by ongoing randomised trials. In the case of patients with moderate-large volume infarction such as occurs often with cardioembolic stroke, there is concern that anticoagulation may increase the risk of haemorrhagic transformation of the infarct, and a delay of an arbitrary 2-week period has been recommended in previous editions of this guideline. Observational data have suggested a lower rate of the composite outcome of recurrent stroke, bleeding or symptomatic ICH when anticoagulation is started between days 4 and 14 compared to within 4 days of AF-associated stroke (Paciaroni et al, 2015). Cohort studies suggest that commencing anticoagulation with a DOAC may be safe between days 4 and 14 in patients with small- or medium-sized infarcts, at least (Gioia et al, 2016; Labovitz et al, 2021). Pooled data analysis of over 2,500 patients in European and Japanese prospective cohort studies showed no increase in ICH when a DOAC was started earlier (within 5 days) rather than later in people with AF-associated stroke (De Marchis et al, 2022). Such observational studies are vulnerable to selection bias and confounding by indication, but they suggest that for patients with minor stroke (e.g. NIHSS 0-3) and a lower risk of haemorrhagic transformation it may be appropriate to commence treatment sooner, at the discretion of the treating clinician. Recent evidence from the TIMING randomised trial showed early initiation of anticoagulation with a DOAC in people with AF-related stroke was non-inferior to delayed initiation, with no ICH in either group (Oldgren et al, 2022), although the majority of strokes in both groups were mild (median NIHSS of 4 in both groups). Definitive guidance, particularly in relation to moderate-severe stroke, must await the findings from RCTs addressing the issue of early versus late initiation in people with AF-related stroke that have either recently completed (e.g. ELAN: NCT03148457) or are ongoing (e.g. OPTIMAS: NCT03759938), and a planned individual participant data meta-analysis. [2023]

There is strong evidence for the use of anticoagulation for long-term secondary prevention of stroke in people with permanent AF (Saxena & Koudstaal, 2004), and the 12% risk of recurrent stroke per year (EAFT Study Group, 1993) substantially alters the balance of risk and benefit in favour of anticoagulation in almost every instance. In people with relative contraindications to anticoagulation identified through the use of a validated tool (e.g. HAS-BLED; (Pisters et al, 2010) or MICON-ICH; Best et al., 2021) it may be possible to intervene to reduce the bleeding risk through control of blood pressure, medication review, treatment of other conditions and multidisciplinary input to reduce risk of falls and improve medication adherence. Falls are associated with higher risk of injury and bleeding but the risk is very unlikely to outweigh the benefits of anticoagulation for stroke prevention (Man-Son-Hing et al, 1999) The safety and benefit of DOACs over VKA is maintained in people with a history of falls in the available RCT evidence (Steffel et al, 2016; Rao et al, 2018). Single-centre data also suggest a reduced risk of traumatic brain injury in people with a history of falls on DOACs compared with VKA (Scotti et al. 2019). Other imaging biomarkers that may influence the balance of risk and benefit from anticoagulation in individual patients are considered in Section 5.21 Cerebral microbleeds. [2023]

DOACs are rapidly replacing VKAs for secondary stroke prevention in people with non-valvular AF. These medications have a rapid onset of action, have fewer interactions with other medications and foodstuffs, do not require coagulation monitoring and are more patient-friendly. Meta-analysis of the four primary DOAC trials, RE-LY (Connolly et al, 2009), ROCKET AF (Patel et al, 2011), ARISTOTLE (Granger et al, 2011) and ENGAGE AF-TIMI 48 (Giugliano et al, 2013) involving over 70,000 patients, has shown significantly greater stroke and thromboembolic prevention (RR 0.81, 95% CI 0.73 to 0.91; p<0.0001), with a substantially reduced risk of intracranial bleeding compared to warfarin (Ruff et al, 2014). No age interaction was observed for efficacy or safety with any DOAC with the exception of standard dose dabigatran and excess GI bleeding (Eikelboom et al, 2011; Graham et al, 2015). Subsequent meta-analyses with almost three million patient-years of observation have shown consistently better safety with DOACs compared to VKA (Hirschl & Kundi, 2019; Xu et al, 2021) and possibly better efficacy overall (Makam et al, 2018; Shen et al, 2020). [2023]

Given the high attributable risk of recurrent stroke in people with AF, unmodifiable relative contraindications (e.g. age, history of stroke) should not dissuade prescribers from the use of anticoagulation, as these patients are also at greatest of recurrent stroke (Olesen et al, 2011). Older people (aged 65 years or older) with AF have a reduced risk of stroke and thromboembolism on anticoagulant treatment compared to no treatment (relative risk 0.59, 95% CI 0.51 to 0.76, I2 = 12.3%), and with a DOAC rather than a VKA (Bai et al, 2018). If, despite addressing modifiable risk factors for bleeding, the bleeding risk is still considered to be too high to use an anticoagulant safely, then aspirin cannot be regarded as a safer alternative, particularly among older patients (Mant et al, 2007). A current NICE guideline does not recommend the routine use of aspirin in these circumstances aside from when there are other indications unrelated to AF (NICE, 2021c). However, a recent systematic review and meta-analysis of antiplatelet use in patients with AF not treated with anticoagulation (Benz et al, 2022) identified an increased risk of major bleeding and intracerebral haemorrhage, and a reduced risk of myocardial infarction compared to no treatment, suggesting that in selected patients with a low or normal risk of bleeding and a higher risk of vaso-occlusive disease (such as in secondary vascular prevention), antiplatelet treatment may still be appropriate. There may be an emerging role for very low dose edoxaban in achieving an acceptable balance of overall benefit and risk in such patients (Okumura et al, 2020). [2023]

Bearing in mind that participants in all the original comparative trials of DOACs with warfarin had to be eligible for both treatments, the trials do not provide evidence regarding the safety or efficacy of DOACs in people for whom the bleeding risk is considered to be too high to safely use warfarin. However, such patients were included in the AVERROES trial comparing apixaban with aspirin (Connolly et al, 2011), and very low dose edoxaban (15 mg OD) in a high-risk elderly Japanese population appears to be effective and relatively safe (Okumura et al, 2020). [2023]

For selected patients with AF who cannot be treated with anticoagulation, it may be appropriate to consider a left atrial appendage occlusion device if the short-term use of antiplatelets/anticoagulation required following the procedure can be tolerated. In the PROTECT AF trial percutaneous left atrial appendage occlusion with a filter device (Watchman) was non-inferior to warfarin for stroke prevention in people with non-valvular AF (Holmes et al, 2009; Reddy et al, 2013). Device implantation was accompanied by warfarin anticoagulation for the first 45 days. No trials have compared left atrial appendage occlusion with DOAC treatment. [2023]

For people with mechanical heart valves or rheumatic heart disease-associated AF, VKA remains the anticoagulant of choice as DOACs have been shown to be inferior in these situations (Eikelboom et al, 2013; Connolly et al, 2022). There is evidence that combining antiplatelet medication with warfarin reduces the risk of thromboembolic complications, but with an increased risk of bleeding (Little & Massel, 2003; Dentali et al, 2007). Apart from some high-risk patients with mechanical heart valves and patients in AF requiring antiplatelet therapy after coronary stenting, there is no evidence that combining antiplatelet medication with warfarin is beneficial, but there is clear evidence of harm (Hart et al, 2005). [2023]

Implications

This guideline is likely to lead to an increase in the prescribing of DOACs, which are expensive but considered cost-effective by NICE and SMC, particularly when used for secondary prevention where the attributable risk of stroke is several times higher than in primary prevention.  Management of patients with TIA or ischaemic stroke in association with AF requires an interdisciplinary team approach to stroke prevention with close collaboration between stroke physicians/neurologists, cardiologists, general practitioners, pharmacists, specialist nurses. [2023]

5.8 Other risk factors

In about a quarter of people with stroke, and more commonly in younger age groups, no cause is evident on initial investigation.  Other causes that should be considered include par...

5.9 Paroxysmal atrial fibrillation

All forms of atrial fibrillation (AF) represent a potentially significant risk for stroke.  AF may be intermittent and not immediately evident.  It can be classified as paroxysmal ...

Recommendations
A

Patients with ischaemic stroke or TIA not already diagnosed with atrial fibrillation or flutter should undergo an initial period of cardiac monitoring for a minimum of 24 hours if they are appropriate for anticoagulation. [2023]

B

Patients with ischaemic stroke or TIA, in whom no other cause of stroke has been found after comprehensive neurovascular investigation (stroke of undetermined aetiology or ‘cryptogenic’ stroke) and in whom a cardioembolic cause is suspected, should be considered for more prolonged sequential or continuous cardiac rhythm monitoring with an external patch, wearable recorder or implantable loop recorder if they are appropriate for anticoagulation. [2023]

Sources, evidence to recommendations, implications

5.10 Patent foramen ovale

A patent foramen ovale (PFO) may predispose people to a TIA or stroke by acting as a conduit for paradoxical embolism of thrombus, fat or air from the venous into the arterial circ...

Recommendations
A

People with ischaemic stroke or TIA and a PFO should receive optimal secondary prevention treatment, including antiplatelet therapy, treatment for high blood pressure, lipid-lowering therapy and lifestyle modification.  Anticoagulation is not recommended unless there is another recognised indication. [2023]

B

Selected people below the age of 60 with ischaemic stroke or TIA of otherwise undetermined aetiology, in association with a PFO and a right-to-left shunt or an atrial septal aneurysm, should be considered for endovascular PFO device closure within six months of the index event to prevent recurrent stroke.  This decision should be made after careful consideration of the benefits and risks by a multidisciplinary team including the patient’s physician and the cardiologist performing the procedure.  The balance of risk and benefit from the procedure, including the risk of atrial fibrillation and other recognised peri-procedural complications should be fully considered and explained to the person with stroke. [2023]

C

People older than 60 years with ischaemic stroke or TIA of otherwise undetermined aetiology and a PFO should preferably be offered closure in the context of a clinical trial or prospective registry. [2023]

Sources, evidence to recommendations, implications

5.11 Other cardioembolism

Between 20-30% of ischaemic strokes can be attributed to cardioembolism (Sandercock et al, 1989; Kolominsky-Rabas et al, 2001), with the majority of these accounted for by AF. A va...

Recommendations
A

People with stroke or TIA should be investigated with transthoracic echocardiography if the detection of a structural cardiac abnormality would prompt a change of management and if they have:

  • clinical or ECG findings suggestive of structural cardiac disease that would require assessment in its own right, or
  • unexplained stroke or TIA, especially if other brain imaging features suggestive of cardioembolism are present. [2016]
Sources, evidence to recommendations, implications

5.12 Vertebral artery disease

Stroke in the vertebrobasilar territory accounts for 20% of all strokes and is more often associated with corresponding large artery stenosis than is the case for carotid territory...

Recommendations
A

People with ischaemic stroke or TIA and symptomatic vertebral artery stenosis should receive optimal secondary prevention including antithrombotic therapy, blood pressure treatment, lipid-lowering therapy and lifestyle modification.  Angioplasty and stenting of the vertebral artery should only be offered in the context of a clinical trial. [2016]

Sources, evidence to recommendations, implications

5.13 Intracranial artery stenosis

In Western populations, atherosclerotic stenosis of the large intracranial arteries is found in about 40% of patients with ischaemic stroke and is likely to be causative in about 7...

Recommendations
A

People with ischaemic stroke or TIA due to severe symptomatic intracranial stenosis should be offered dual antiplatelet therapy with aspirin and clopidogrel for the first three months in addition to optimal secondary prevention including blood pressure treatment, lipid-lowering therapy and lifestyle modification.  Endovascular or surgical intervention should only be offered in the context of a clinical trial. [2016]

Sources, evidence to recommendations, implications

5.14 Oral contraception and hormone replacement therapy

The observation that stroke tends to affect women at a later age than men raises the possibility that female sex hormones, and specifically oestrogens, might protect against vascul...

5.14.1 Oral contraception

Recommendations
A

Premenopausal women with stroke and TIA should not be offered the combined oral contraceptive pill.  Alternative hormonal (progestogen-only) and non-hormonal contraceptive methods should be considered instead. [2016]

Sources, evidence to recommendations, implications

5.14.2 Hormone replacement therapy

Recommendations
A

Post-menopausal women with ischaemic stroke or TIA who wish to start or continue hormone replacement therapy should receive advice based on the overall balance of risk and benefit, taking account of the woman’s preferences. [2016]

B

Post-menopausal women with ischaemic stroke or TIA should not be offered hormone replacement therapy for secondary vascular prevention. [2016]

Sources, evidence to recommendations, implications

5.15 Obstructive sleep apnoea

There is a prevalence of obstructive sleep apnoea (OSA) of between 30 and 70% in people with ischaemic or haemorrhagic stroke, depending upon the diagnostic criteria used (Johnson ...

Recommendations
A

People with stroke or TIA should be screened for obstructive sleep apnoea with a valid clinical screening tool.  People who screen positive who are suspected of having sleep apnoea should be referred for specialist respiratory/sleep medicine assessment. [2016]

Sources, evidence to recommendations, implications

5.16 Antiphospholipid syndrome

Antiphospholipid syndrome (APS) is an autoimmune disorder which may occur with or without associated rheumatic disease, particularly systemic lupus erythematosus. Patients with APS...

Recommendations
A

People with ischaemic stroke or TIA in whom other conditions such as atrial fibrillation and large or small vessel atherosclerotic disease have been excluded should be investigated for antiphospholipid syndrome (with IgG and IgM anticardiolipin ELISA and lupus anticoagulant), particularly if the person:

  • is under 50 years of age;
  • has any autoimmune rheumatic disease, particularly systemic lupus erythematosus;
  • has a history of one or more venous thromboses;
  • has a history of recurrent first trimester pregnancy loss or at least one late pregnancy loss (second or third trimester). [2016]
B

People with antiphospholipid syndrome who have an ischaemic stroke or TIA:

  • should be managed acutely in the same way as people without antiphospholipid syndrome;
  • should have decisions on long-term secondary prevention made on an individual basis in conjunction with appropriate specialists including haematology and/or rheumatology. [2016]
Sources, evidence to recommendations, implications

5.17 Insulin resistance

Insulin resistance is a component of the metabolic syndrome in which a diminished target cell response to insulin results in a compensatory increase in insulin secretion to maintai...

Recommendations
A

People with stroke or TIA should not receive pioglitazone for secondary vascular prevention. [2016]

Sources, evidence to recommendations, implications

5.18 Fabry disease

Fabry disease is a multi-system disorder in which reduced activity of the enzyme α-galactosidase leads to the accumulation of glycolipid in various organs damaging tissues, particu...

Recommendations
A

Young people with stroke or TIA should be investigated for Fabry disease if they have suggestive clinical features such as acroparesthesias, angiokeratomas, sweating abnormalities, corneal opacities, unexplained renal insufficiency or a family history suggesting the condition. [2016]

B

People with stroke or TIA and a diagnosis of Fabry disease should receive optimal secondary prevention and be referred to specialist genetic and metabolic services for advice on other aspects of care including the provision of enzyme replacement therapy. [2016]

Sources, evidence to recommendations, implications

5.19 Cerebral Amyloid Angiopathy

Sporadic cerebral amyloid angiopathy (CAA), a common age-related cerebral small vessel disease, is an important cause of lobar intracerebral haemorrhage (ICH), particularly in olde...

Recommendations
A

Patients with lobar ICH associated with probable CAA should be considered for blood pressure lowering to below a long-term target of 130/80 mmHg.  Wherever possible patients should be offered participation in a randomised trial of blood pressure-lowering treatment. [2023]

B

Patients with lobar ICH associated with probable CAA may be considered for antiplatelet therapy for the secondary prevention of vaso-occlusive events, but wherever possible patients should be offered participation in a randomised trial.  If participation in a randomised trial is not possible then clinicians should make an individualised decision based on estimates of the future risks of recurrent ICH and vaso-occlusive events. [2023]

C

Patients with lobar ICH associated with probable CAA and AF may be considered for oral anticoagulation for stroke prevention, but wherever possible patients should be offered participation in a randomised trial.  If participation in a randomised trial is not possible then clinicians should make an individualised decision based on estimates of the future risks of recurrent ICH and vaso-occlusive events. [2023]

D

Patients with lobar ICH associated with probable CAA and AF may be considered for a left atrial appendage occlusion (LAAO) device, but wherever possible patients should be offered participation in a randomised trial.  If participation in a randomised trial is not possible then LAAO may be considered based on an estimation of the future risks of recurrent ICH and vaso-occlusive events. [2023]

Sources, evidence to recommendations, implications

5.20 CADASIL

CADASIL (cerebral autosomal dominant arteriopathy with subcortical infarcts and leucoencephalopathy) is caused by mutations in the NOTCH3 gene, and is the most common single gene d...

Recommendations
A

People with clinical and radiological features that are suggestive of CADASIL should only be offered genetic testing after appropriate counselling and discussion.  Predictive testing in other family members should be performed by a specialist clinical genetics service after appropriate counselling. [2023]

B

People with CADASIL should be considered for intensive cardiovascular risk factor management, particularly with respect to blood pressure management (target to below 130/80 mmHg) and smoking cessation advice.  They should also be considered for active management of other risk factors including lipid lowering treatment (including with statins), and diabetes mellitus, and offered lifestyle advice (including regarding obesity and exercise). [2023]

C

People with CADASIL and ischaemic stroke or TIA may be considered for antiplatelet therapy; cerebral microbleeds are not a contraindication. [2023]

Sources, evidence to recommendations, implications

5.21 Cerebral microbleeds

Cerebral microbleeds are small haemosiderin deposits detected by blood-sensitive MRI scans including T2-weighted gradient recalled echo and susceptibility-weighted imaging (SWI), T...

Recommendations
A

In patients with ischaemic stroke or TIA requiring antiplatelet or anticoagulant treatment, the presence of cerebral microbleeds (regardless of number or distribution) need not preclude antithrombotic medication use. [2023]

B

In patients with recent ischaemic stroke or TIA treated with antithrombotic (i.e. antiplatelet or anticoagulant) medication, the use of a validated risk score (such as the MICON-ICH score) may be considered for predicting the risk of symptomatic intracranial haemorrhage to allow the mitigation of bleeding risk, including assertive management of modifiable factors (e.g. hypertension, alcohol intake and review of concurrent medication). [2023]

Sources, evidence to recommendations, implications

5.22 Lifestyle measures

The evidence for lifestyle interventions relates mainly to the primary prevention of vascular events; little high quality research has studied the secondary prevention of stroke or...

5.23 Physical activity

People who have sustained a stroke often become physically deconditioned, with low cardiorespiratory fitness, muscle strength and muscle power (Smith et al, 2012; Saunders et al, 2...

Recommendations
A

People with stroke or TIA should participate in physical activity for fitness unless there are contraindications.  Exercise prescription should be individualised, and reflect treatment goals and activity recommendations. [2016]

B

People with stroke or TIA should aim to be active every day and minimise the amount of time spent sitting for long periods. [2016]

C

People with stroke should be offered cardiorespiratory training or mixed training regardless of age, time since having the stroke, and severity of impairment.

  • Facilities and equipment to support high-intensity (greater than 70% peak heart rate) cardiorespiratory fitness training (such as bodyweight support treadmills, or static or recumbent cycles) should be available;
  • The dose of training should be at least 30-40 minutes, 3 to 5 times a week for 10-20 weeks;
  • Programmes of mixed training (medium intensity cardiorespiratory [40%-60% of heart rate reserve] and strength training [50-70% of one-repetition maximum]) such as circuit training classes should also be available at least 3 days per week for 20 weeks;
  • The choice of programme should be guided by patients’ goals and preferences and delivery of the programme individualised to their level of impairment and goals. [2023]
D

People with stroke or TIA who are at risk of falls should engage in additional physical activity which incorporates balance and co-ordination, at least twice per week. [2016]

E

Physical activity programmes for people with stroke or TIA should be tailored to the individual after appropriate assessment, starting with low-intensity physical activity and gradually increasing to moderate levels. [2016]

F

Physical activity programmes for people with stroke or TIA may be delivered by therapists, fitness instructors or other appropriately trained people, supported by interagency working where possible.  When delivered outside statutory health services, physical fitness training should be delivered by professionals with appropriate education and training in stroke and exercise (e.g. Chartered Institute for the Management of Sport and Physical Activity [CIMSPA]-endorsed exercise professionals or clinical exercise physiologists). [2023]

G

Stroke rehabilitation services should build links with community-based exercise facilities (such as support groups, gyms, leisure centres or exercise referral schemes) to support people with stroke to transition to ongoing physical activity on completion of an exercise programme. [2023]

H

Stroke services should consider working with other established rehabilitation services, such cardiac or pulmonary rehabilitation, to develop exercise-based programmes and ensure access to equipment and screening protocols. [2023]

Sources, evidence to recommendations, implications

5.24 Smoking cessation

About 1 in 5 adults in the UK and Ireland are smokers (Department of Health (Ireland), 2021; Office of National Statistics, 2022). Each year, an estimated 454,700 hospital admissio...

Recommendations
A

People with stroke or TIA who smoke should be advised to stop immediately.  Smoking cessation should be promoted in an individualised prevention plan using interventions which may include pharmacotherapy, psychosocial support and referral to statutory stop smoking services. [2016]

Sources, evidence to recommendations, implications

5.25 Nutrition (secondary prevention)

Long-term adherence to cardioprotective diets, when combined with other lifestyle modifications, may reduce stroke recurrence (Appel et al, 1997; Appel et al, 2003; Fung et al, 200...

Recommendations
A

People with stroke or TIA should be advised to eat an optimum diet that includes:

  • five or more portions of fruit and vegetables per day from a variety of sources;
  • two portions of oily fish per week (salmon, trout, herring, pilchards, sardines, fresh tuna). [2016]
B

People with stroke or TIA should be advised to reduce and replace saturated fats in their diet with polyunsaturated or monounsaturated fats by:

  • using low-fat dairy products;
  • replacing butter, ghee and lard with products based on vegetable and plant oils;
  • limiting red meat intake, especially fatty cuts and processed meat. [2016]
C

People with stroke or TIA who are overweight or obese should be offered advice and support to aid weight loss including adopting a healthy diet, limiting alcohol intake to 2 units a day or less and taking regular exercise.  Targeting weight reduction in isolation is not recommended. [2016]

D

People with stroke or TIA should be advised to reduce their salt intake by:

  • not adding salt to food at the table;
  • using little or no salt in cooking;
  • avoiding high-salt foods, e.g. processed meat such as ham and salami, cheese, stock cubes, pre-prepared soups and savoury snacks such as crisps and salted nuts. [2016]
E

People with stroke or TIA who drink alcohol should be advised to limit their intake to 14 units a week, spread over at least three days. [2016]

F

Unless advised to do so for other medical conditions, people with stroke or TIA should not routinely supplement their diet with:

  • B vitamins or folate;
  • vitamins A, C, E or selenium;
  • calcium with or without vitamin D. [2016]
Sources, evidence to recommendations, implications

5.26 Life after stroke

Stroke research has tended to concentrate on the acute and early phases of recovery yet for about half of those who survive, life after stroke involves some permanent impairment an...

5.27 Further rehabilitation

Following discharge from rehabilitation, many people with stroke experience a discontinuity in their care (Hartford et al, 2019) whilst still adjusting to life after stroke. In add...

Recommendations
A

People with stroke, including those living in a care home, should be offered a structured, holistic review of their individual needs by a healthcare professional with appropriate knowledge and skills, using an appropriate mode of communication (e.g. face-to-face, by telephone or online).

  • This review should cover physical, neuropsychological and social needs, seek to identify what matters most to the person, and be undertaken at 6 months after stroke, or earlier if requested by the person with stroke.
  • At this 6-month review, the reviewer should discuss with the person with stroke who would be best placed to undertake the next review at 1 year post-stroke (or at another point in time, depending on the person’s needs), as well as the agreed mode of communication.
  • This review should be offered annually thereafter (or at another point in time, if requested by the person with stroke), for as long as a need for ongoing review continues and on request thereafter. [2023]
B

People with stroke who have further needs identified at a 6-month or subsequent review should be considered for intervention or referral for health or social care assessment if:

  • new health or social care needs are identified;
  • existing health or social care needs have escalated;
  • further rehabilitation goals related to specific physical, psychological, vocational, family or social needs can be identified and agreed;
  • risk factors or co-morbidities are identified that would lead to deterioration if no action were taken. [2023]
C

People with stroke who have further needs identified at a 6-month or subsequent review that do not require health or social care input should be provided with information about or referred to other appropriate services to address their needs (e.g. community-based support groups provided by voluntary or statutory services).  Healthcare professionals should discuss with the person if they could facilitate the transition with their agreement (e.g. by providing relevant information to the service, or by a scheduling a joint session). [2023]

D

Healthcare professionals providing 6-month or subsequent reviews of people with stroke should maintain an up-to-date overview of appropriate health and social care services, and other service providers (e.g. community support groups and local councils) to facilitate transitions to other services as required. [2023]

E

People with stroke should be provided with the contact details of a named healthcare professional (e.g. a stroke co-ordinator or key worker) who can provide further information, support and advice, as and when needed. [2023]

F

People with stroke should be supported to develop their own self-management plan, based on their individual needs, goals, preferences and circumstances. [2023]

G

People with stroke who are unable to undertake their own self-management should be referred in a timely manner to appropriate health, social care, or other voluntary or statutory services depending on their needs. [2023]

Sources, evidence to recommendations, implications

5.28 Social integration and participation

Helping people with stroke to integrate back into the community in the way that they want is a key goal of healthcare; engagement in community activity is associated with improved ...

Recommendations
A

As part of their self-management plan, people with stroke should be supported to identify social and leisure activities that they wish to participate in, taking into account their cognitive and practical skills.  Healthcare professionals should:

  • advise the person with stroke and their family/carers about the benefits of participating in social and leisure activities;
  • identify and help them to overcome any barriers to participation (e.g. low self-confidence or lack of transport). [2016]
B

People with stroke should be provided with information and referral to statutory and voluntary community organisations that can support the person in social participation. [2016]

C

People with stroke whose social behaviour is causing distress to themselves or others should be assessed by an appropriately trained healthcare professional to determine the underlying cause and advise on management.  Following the assessment:

  • the nature of the problem and its cause should be explained to family/carers, other people in social contact and the rehabilitation team;
  • the person should be helped to learn the best way to interact without causing distress;
  • those involved in social interactions should be trained in how to respond to inappropriate or distressing behaviour;
  • psychosocial management approaches should be considered;
  • antipsychotic medicines may be indicated if other causes have been excluded and the person is at risk of harm to themselves or others. The balance of risk and benefit from antipsychotic medication should be carefully considered.  Treatment should be started with a low dose and increased slowly according to symptoms, and should be short-term (e.g. one week) or intermittent and withdrawn slowly. [2016]
Sources, evidence to recommendations, implications