Ischemic stroke

Overview 
Theory 
Diagnosis 
Management 
Follow up 
Resources 

Please note that formulations/routes and doses may differ between drug names and brands, drug formularies, or locations. Treatment recommendations are specific to patient groups: see disclaimer

ACUTE

without cerebral venous sinus thrombosis

presentation within 4.5 hours and no contraindication to intravenous thrombolysis

1st line – recombinant tissue plasminogen activator (r-tPA)

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1st line –

recombinant tissue plasminogen activator (r-tPA)

There are currently two formulations of r-tPA available for the management of ischemic stroke: alteplase and tenecteplase. Both are approved in the US and Europe for the management of acute ischemic stroke.

Tenecteplase is similar to alteplase but is more fibrin specific, more resistant to plasminogen activator inhibitor, and has a longer duration of action. Alteplase and tenecteplase promote thrombolysis, and thereby recanalization and reperfusion.

Early administration of intravenous alteplase or tenecteplase is recommended for appropriate patients who meet the defined criteria for thrombolysis.[135] Tenecteplase is at least as effective and safe as alteplase.[163][164][165][166][167][168][169]

Early initiation of intravenous thrombolysis (i.e., within 4.5 hours of onset of symptoms, if it is not contraindicated) is associated with improved functional outcomes.[170][171] In a retrospective cohort study of more than 61,000 patients aged 65 years or older with acute ischemic stroke, shorter door-to-needle times were associated with lower all-cause mortality and lower all-cause readmission at 1 year.[171] Trials of alteplase suggest that the ideal window of opportunity for thrombolysis for patients with acute ischemic stroke and no contraindications is up to 4.5 hours after the onset of neurologic symptoms.[135][172] For patients with severe acute stroke, goal time from emergency department arrival to initiation of intravenous thrombolysis (if indicated) is 60 minutes.[130][173]

The American Heart Association/American Stroke Association (AHA/ASA) recommend alteplase with 4.5 hours of known onset of stroke symptoms and recommend to consider tenecteplase as an alternative to alteplase in patients with minor neurologic impairment and no major intracranial occlusion.[135] This is based on guidelines that were published before the approval of tenecteplase in the US and you should consult local protocols for choice of thrombolytic agent. Although benefit with tenecteplase has been shown in patients presenting within 4.5 hours of onset, caution should be exercised in patients with minor stroke (NIHSS score 0-5) presenting between 4.5 and 12 hours from stroke onset.[169][174]

In Europe, alteplase is approved for use between 4.5 and 9 hours of known onset or within 9 hours of the midpoint of sleep in patients who have woken with symptoms with computed tomography (CT) or magnetic resonance imaging (MRI) core/perfusion mismatch.[175][176] In Europe, tenecteplase is recommended for use within 4.5 hours of known onset of acute ischemic stroke.[163][175][176]

Orolingual edema is a rare but potentially serious complication.

Blood glucose should be normalized before initiating alteplase treatment.[135] Administration should not be delayed by additional tests unless a specific contraindication is suspected and must be ruled out.

In the frequent situation where the onset of symptoms was not witnessed, the time of onset must be presumed to be the time at which the patient was last witnessed to be well.

The AHA/ASA state that the eligibility recommendations for treating with intravenous alteplase are:[135]

(1) Within 4.5 hours of stroke symptom onset or patient last known well or at baseline state: patients with severe stroke symptoms or mild but disabling stroke symptoms; those without a history of both diabetes mellitus and stroke; those with a baseline National Institutes of Health Stroke Scale (NIHSS) score ≤25; those not taking any oral anticoagulants; those without imaging evidence of ischemic injury involving more than one third of the middle cerebral artery territory.

The AHA/ASA further recommend that candidates for intravenous thrombolysis with alteplase should be: patients whose blood pressure can be lowered safely to <185/110 mmHg with antihypertensive agents; those with initial glucose levels >50 mg/dL; patients with early ischemic changes on noncontrast CT of mild to moderate extent (other than frank hypodensity); patients who have had antiplatelet monotherapy or combination therapy before stroke, provided the benefit of alteplase outweighs the possible increased risk of symptomatic intracerebral hemorrhage; patients with end-stage renal disease on hemodialysis and normal aPTT.[135]

Additional recommendations for treatment with intravenous thrombolysis can be found in the AHA/ASA guidelines.[135]

When treating a patient with major deficits, the likelihood of favorable outcome is reduced and there is increased risk of hemorrhage following thrombolysis.[135] Evidence shows that patients aged over 80 years derive as much benefit (reduced death or dependency, improved functional outcomes) from intravenous alteplase as do those aged under 80 years, especially if treated within 3 hours of stroke.[170][183][184]

These AHA/ASA guidelines on eligibility for alteplase were published before the approval of tenecteplase in the US. You should consult a specialist for guidance on eligibility criteria for tenecteplase.

Information on the benefits and risks of intravenous thrombolysis should be given to the patient, if competent, or to a surrogate decision-maker, if present. Verbal or written consent should be obtained if feasible. In the frequent situation where the patient is not competent to make medical decisions, and family or a surrogate decision-maker cannot be identified or approached in a timely manner, it is justifiable to proceed with intravenous thrombolysis in an otherwise eligible adult patient with a disabling ischemic stroke.[135] If a patient lacks decisional capacity, does not have a determinative advance directive (one that offers guidance in this usually unanticipated situation), and no authorized surrogate is available, interventions may be provided based on the ethical and common law presumption of consent; that is, the rationale that reasonable people would consent to treatment if they could be asked. The imminent risk of significant disability also justifies emergent treatment in these circumstances.[177] Severe baseline functional (cognitive and/or medical) disability may minimize the potential benefits of endovascular intervention.[175]

Decision-makers should be informed that intravenous thrombolysis treatment is associated with a better outcome in around 1 in 3 people treated, and with a worse outcome in around 3 in 100 people treated.[179] Overall, 1 in 8 people treated with intravenous thrombolysis have a complete or near-complete recovery who otherwise would have been disabled.[180] The absence of definitive evidence on the efficacy of thrombolysis and endovascular therapy in patients with premorbid disability or dementia results in difficult decisions about the use of these therapies. A pragmatic case-by-case approach is recommended in these patients.[181]

Primary options

alteplase: 0.9 mg/kg total dose intravenously, administer 10% of dose as a bolus, with the remaining 90% infused over 1 hour, maximum 90 mg total dose

tenecteplase: <60 kg body weight: 15 mg intravenously as a single dose; 60-69 kg body weight: 17.5 mg intravenously as a single dose; 70-79 kg body weight: 20 mg intravenously as a single dose; 80-89 kg body weight: 22.5 mg intravenously as a single dose; ≥90 kg body weight: 25 mg intravenously as a single dose

Plus – antiplatelet therapy

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Plus –

antiplatelet therapy

Treatment recommended for ALL patients in selected patient group

All ischemic stroke patients should receive aspirin.[135] Patients who are given intravenous thrombolysis should not usually start aspirin until 24 hours afterwards, and only then after a head CT shows the absence of intracranial hemorrhage.[135][185][277]

For patients with noncardioembolic ischemic stroke or transient ischemic attack (TIA), guidelines from the American Heart Association/American Stroke Association (AHA/ASA) recommend aspirin, clopidogrel, or the combination of aspirin plus extended-release dipyridamole for secondary prevention of ischemic stroke.[113] In patients with recent minor (NIHSS score ≤3) noncardioembolic ischemic stroke or high-risk TIA (ABCD2 score ≥4), the AHA/ASA recommend that dual antiplatelet therapy should be initiated early (ideally within 12-24 hours of symptom onset and at least within 7 days of onset) and continued for 21-90 days, followed by single antiplatelet therapy, to reduce the risk of recurrent ischemic stroke.[113][135][186][187] The dual antiplatelet therapy regimen of ticagrelor plus aspirin is approved in the US by the Food and Drug Administration (FDA) to reduce the risk for stroke in patients with acute ischemic stroke with a NIHSS score of ≤5 or high-risk TIA. In Europe, an application to the European Medicines Agency (EMA) to change the marketing authorization of ticagrelor to include the prevention of stroke in adults who have had a mild to moderate ischemic stroke or high-risk TIA was withdrawn in December 2021. Based on trial data and the company’s response to their questions, the EMA expressed concern that the benefits of short-term treatment with ticagrelor plus aspirin in preventing stroke in these patients did not clearly outweigh the risks of fatal and nonfatal bleeding.

Antiplatelet therapy with aspirin or clopidogrel (either alone or with patent foramen ovale closure), is recommended for the secondary prevention of stroke in patients with cryptogenic ischemic stroke secondary to patent foramen ovale (PFO).[234] In patients with a high risk of paradoxical embolism (RoPE) score, closure of the PFO reduces stroke recurrence compared with medical treatment alone.[236][237][238][239]

All patients with previous stroke should be treated with an antithrombotic indefinitely if there is no bleeding contraindication, regardless of whether a PFO is present or if it is closed. For patients aged under 60 years, PFO closure plus antiplatelet therapy is likely to be of benefit for secondary stroke prevention compared with anticoagulant therapy.[235] PFO closure plus antiplatelet therapy is preferred to antiplatelet therapy alone if anticoagulation is contraindicated or declined.[235][240] See Patent foramen ovale.

In patients with a stroke or TIA caused by 50% to 99% stenosis of a major intracranial artery, aspirin is recommended in preference to warfarin to reduce the risk of recurrent ischemic stroke and vascular death.[24][113] In patients with recent stroke or TIA (within 30 days) attributable to severe stenosis (70% to 99%) of a major intracranial artery, the addition of clopidogrel to aspirin for up to 90 days is recommended to further reduce recurrent stroke risk in patients who have low risk of hemorrhagic transformation.[24][113] In patients with recent (within 24 hours) minor stroke or high-risk TIA and concomitant ipsilateral >30% stenosis of a major intracranial artery, the addition of ticagrelor to aspirin for up to 30 days might be considered to further reduce recurrent stroke risk.[113] Carotid artery endarterectomy (CEA) and carotid artery stenting (CAS) may be indicated in selected patients. See Carotid artery stenosis.

Some guidelines recommend CYP2C19 genotype testing to assess if clopidogrel is a suitable antiplatelet drug for people who have just had an ischemic stroke or a transient ischemic attack (TIA).[192] When interpreting test results, the prevalence of different CYP2C19 genotypes may vary between ethnic groups should be taken into account.

Consult specialist or local protocols for guidance on the choice of an appropriate antiplatelet regimen and doses.

Plus – high-intensity statin

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Plus –

high-intensity statin

Treatment recommended for ALL patients in selected patient group

Statin therapy with intensive lipid-lowering effects is recommended for patients with ischemic stroke or TIA, to lower the risk of stroke and cardiovascular events.[113][246] Statin treatment should not be started immediately. There is consensus that it is safe to start statins after 48 hours.[151] Statin treatment should be continued in people who are already receiving statins.[151]

There is evidence that the rate of recurrent cardiovascular events or stroke is lower in patients whose low density lipoprotein (LDL) is controlled to <70 mg/dL compared with those with LDL between 90 and 110 mg/dL.[24][247] Monitoring of liver enzymes is recommended for patients taking statins. Caution should be exercised when prescribing high-intensity statins to patients with a history of intracerebral hemorrhage.

In patients with ischemic stroke with no known coronary heart disease, no major cardiac sources of embolism, and LDL cholesterol (LDL-C) >100 mg/dL, atorvastatin is indicated to reduce risk of stroke recurrence.[113]

In patients with stroke or TIA and hyperlipidemia, adherence to changes in lifestyle and the effects of LDL-C–lowering drugs should be assessed by measurement of fasting lipids and appropriate safety indicators 4-12 weeks after statin initiation or dose adjustment. This assessment should be repeated every 3-12 months thereafter, based on need to assess adherence or safety.[113]

Primary options

atorvastatin: 40-80 mg orally once daily

Plus – supportive care

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Plus –

supportive care

Treatment recommended for ALL patients in selected patient group

Admission to a dedicated stroke unit, compared with admission to a general medical/surgical service, is associated with improved survival and less disability at 1 year.[263][264] [ ] Stroke units should have multidisciplinary teams, including physicians, nursing staff, and rehabilitation specialists with expertise in stroke. Improved supportive care, avoidance of complications such as infection, and earlier initiation of rehabilitation therapy are among the mechanisms by which stroke units are hypothesized to produce better outcomes.

Supplemental oxygen should be provided only when blood oxygen saturation is <94%. Liberal use of oxygen is associated with increased mortality in acutely sick patients.[248][249] Patients with decreased level of consciousness or refractory hypoxemia may require intubation with mechanical ventilation.[135][250]

Tracheal intubation: animated demonstration

How to insert a tracheal tube in an adult using a laryngoscope.

Bag-valve-mask ventilation: animated demonstration

How to use bag-valve-mask apparatus to deliver ventilatory support to adults. Video demonstrates the two-person technique.

Management of arterial blood pressure (BP) in acute ischemic stroke remains controversial because of conflicting evidence and a lack of large controlled clinical trials.[135] Many patients with ischemic stroke have elevated BP at presentation. Lowering BP could reduce cerebral perfusion pressure and promote stroke extension.[135][254] However, American Heart Association/American Stroke Association (AHA/ASA) guidelines recommend early treatment of hypertension when required by comorbid conditions (e.g., concomitant acute coronary event, acute heart failure, aortic dissection, postfibrinolysis, sICH [symptomatic intracerebral hemorrhage]). Management in these situations should be individualized, but in general, initial BP reduction by 15% is a reasonable goal.[135] In patients with BP of ≥220/120 mmHg who did not receive intravenous thrombolytic or endovascular treatment and have no comorbid conditions requiring acute antihypertensive treatment, it may be reasonable to lower BP by 15% during the first 24 hours after onset of stroke to improve outcomes.[135][212] In patients with BP <220/120 mmHg who do not receive intravenous thrombolysis or endovascular treatment and do not have a comorbid condition requiring emergent antihypertensive treatment, initiating or reinitiating treatment of hypertension within the first 48-72 hours after an ischemic stroke is not effective to prevent death or disability.[212] BP should be maintained below 180/105 mmHg for at least the first 24 hours after initiating thrombolytic therapy to avoid complications.[172][180][212] In patients who undergo endovascular thrombectomy, it is reasonable to maintain blood pressure at ≤180/105 mmHg during and for 24 hours after the procedure to improve long-term functional outcomes and prevent death.[212] In patients undergoing successful brain reperfusion with thrombolysis or endovascular thrombectomy for a large vessel occlusion, lowering systolic BP <140 mmHg within the first 24-72 hours after reperfusion can worsen long-term functional outcome.[212]

Hypoglycemia can cause brain injury and should be avoided. One randomized trial found that in acute ischemic stroke patients with hyperglycemia, aggressive control of glucose levels with intravenous insulin did not result in a significant difference in favorable functional outcome at 90 days compared with standard glucose control, but it was associated with severe hypoglycemia in more patients (2.6%).[257] Hypoglycemia can be well controlled with frequent subcutaneous insulin injections based on a sliding scale.[258]

Hyperglycemia has been associated with poor outcome and risk of hemorrhagic transformation of ischemic stroke.[135][157][158][159] Treatment of significantly elevated blood glucose is recommended since evidence indicates that persistent in-hospital hyperglycemia during the first 24 hours after acute ischemic stroke is associated with worse outcomes than normoglycemia.[135]

Fever may be associated with poor stroke outcome.[135][259] Treatment of fever is, therefore, reasonable, although not yet shown to be effective by controlled trials.[135][260][261][262]

Plus – swallowing assessment

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Plus –

swallowing assessment

Treatment recommended for ALL patients in selected patient group

Swallowing impairment is common in stroke and is associated with an increased risk of aspiration pneumonia and death.[265][266] Guidelines support the use of a bedside swallow test before eating or drinking but do not provide specifics on test administration and interpretation.[135]

A reasonable approach is to withhold oral intake if there is coughing or a wet voice after swallowing a small cup of water.

Patients who cannot take nutrition orally should receive fluids and enteral feeding by nasogastric, nasoduodenal, or percutaneous gastrostomy tube. [ ]

Consider – mechanical thrombectomy

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Consider –

mechanical thrombectomy

Treatment recommended for SOME patients in selected patient group

Endovascular interventions include mechanical clot-removing devices, such as stent retrievers, and intra-arterial thrombolysis. Initiation of endovascular interventions should be carried out as early as possible.[135] Intravenous thrombolysis within 4.5 hours of symptom onset plus mechanical thrombectomy within 6 hours of symptom onset is the standard of care to treat strokes caused by large vessel occlusion (LVO) in patients meeting eligibility criteria.[135][195]Sacks D, Baxter B, Campbell BCV, et al. Multisociety consensus quality improvement revised consensus statement for endovascular therapy of acute ischemic stroke: from the American Association of Neurological Surgeons (AANS), American Society of Neuroradiology (ASNR), Cardiovascular and Interventional Radiology Society of Europe (CIRSE), Canadian Interventional Radiology Association (CIRA), Congress of Neurological Surgeons (CNS), European Society of Minimally Invasive Neurological Therapy (ESMINT), European Society of Neuroradiology (ESNR), European Stroke Organization (ESO), Society for Cardiovascular Angiography and Interventions (SCAI), Society of Interventional Radiology (SIR), Society of NeuroInterventional Surgery (SNIS), and World Stroke Organization (WSO). J Vasc Interv Radiol. 2018 Apr;29(4):441-53.[196] Clinical trials and registry data have proven the efficacy of this approach.[197][198][199][200] The risk of complications with sequelae for patients from mechanical thrombectomy has been estimated to be around 15%; such complications need to be minimized and effectively managed to maximize the benefits of thrombectomy.[201]

The American Heart Association/American Stroke Association (AHA/ASA) guidelines state that patients who are eligible for alteplase should be treated with alteplase even if they are potential candidates for endovascular therapy with a stent retriever.[135] Observing patients for a clinical response to intravenous alteplase prior to use of endovascular therapy should not be performed.[135]

The AHA/ASA guidelines suggest that patients meeting all of the following criteria can be treated with a stent retriever: have a prestroke Modified Rankin Disability Scale score 0-1; have causative occlusion of the internal carotid artery or proximal middle cerebral artery (M1); age ≥18 years; have a National Institutes of Health Stroke Scale score ≥6; have an Alberta Stroke Program Early CT score (ASPECTS) ≥6; and can begin endovascular therapy (groin puncture) within 6 hours of symptom onset.[135]

Endovascular thrombectomy with stent assisted retriever may also be considered for patients who are ages <18 years, or have a Modified Rankin Disability Scale score >1, if initiated within 6 hours of symptom onset, but the potential benefits are unclear as there is a lack of evidence in these patients.[135][178]

The role of thrombectomy alone without intravenous thrombolysis (e.g., where there are contraindications for thrombolysis) has not yet been ascertained if a stroke from a large vessel occlusion has been identified within 4.5 hours of onset. Randomized controlled trials of direct endovascular thrombectomy ≤4.5 hours of stroke onset have not demonstrated noninferiority to bridging therapy (intravenous thrombolysis before endovascular thrombectomy) for functional independence.[202][203][204]

The AHA/ASA recommend the use of stent retrievers over intra-arterial thrombolysis and other mechanical thrombectomy devices (e.g., concentric retrievers) as first-line endovascular therapy for acute ischemic stroke; however, devices other than stent retrievers may be reasonable in some circumstances.[135]

Proximal balloon guide catheter or a large bore distal catheter, rather than a cervical guide catheter alone, in conjunction with stent retrievers may also be useful in certain carefully selected patients.[135] An adjunctive intervention (e.g., intra-arterial thrombolysis) may also be useful to achieve acceptable reperfusion, if used within 6 hours of symptom onset. However, there are no intra-arterial thrombolytic interventions approved for use in stroke.

For patients who otherwise meet criteria for mechanical thrombectomy, noninvasive vessel imaging of the intracranial arteries is recommended during the initial imaging evaluation.[135] Noncontrast CT should be the predominant imaging modality for patient selection since it is fast and readily available. Endovascular thrombectomy is associated with improved functional outcome and lower mortality in patients with acute ischemic stroke from large vessel occlusion with established large infarct identified using noncontrast CT.[205][207][219] Expert consensus opinion from the American College of Radiology recommends against using endovascular intervention when there is evidence of a large irreversible infarction in the territory of the index vessel since the likelihood of procedure-related harm due to reperfusion resulting in hemorrhagic transformation may be higher than in those with smaller baseline infarction.[178] However, recent data from six internationally conducted trials suggest thrombectomy may be useful in selected patients with large ischemic strokes (i.e., Alberta Stroke Program Early CT score [ASPECTS] of 0-5 on noncontrast CT or MRI-DWI).[205][206][219][221][222][223] These trials were conducted in patients ages 18-85 years with acute ischemic stroke from a large vessel occlusion and large core infarctions who received intra-arterial thrombectomy from <6 to 24 hours of onset. Results from all trials showed improved functional outcome and slightly increased intracranial hemorrhage but no difference in mortality.

Consider – anticoagulation

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Consider –

anticoagulation

Treatment recommended for SOME patients in selected patient group

Anticoagulation is an option for the secondary prevention of stroke in specific patient groups with cryptogenic ischemic stroke secondary to nonvalvular atrial fibrillation or patent foramen ovale (PFO).[234] All patients with previous stroke should be treated with an antithrombotic indefinitely if there is no bleeding contraindication, regardless of whether a PFO is present or if it is closed. For patients aged under 60 years, PFO closure plus antiplatelet therapy is likely to be of benefit for secondary stroke prevention compared with anticoagulant therapy.[235] PFO closure plus antiplatelet therapy is preferred to antiplatelet therapy alone if anticoagulation is contraindicated or declined.[235][240] PFO closure may be indicated in some patients. See Patent foramen ovale.

Consider – VTE prophylaxis + early mobilization

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Consider –

VTE prophylaxis + early mobilization

Treatment recommended for SOME patients in selected patient group

Venous thromboembolism (VTE) is the cause of about 10% of stroke deaths.[267]

Intermittent pneumatic compression of the legs is recommended to reduce the risk of deep vein thrombosis (DVT)/VTE in nonambulatory stroke patients.[135][268][269] Elastic compression stockings are not recommended.[135][268]

The benefits of prophylactic subcutaneous heparin in patients with acute ischemic stroke are not well established; it decreases the rate of DVT and pulmonary embolism, but is also associated with a significant increase in the rate of hemorrhage, with no significant effect on mortality or functional status at final follow-up.[135]

Guidelines note that there may be a subgroup of patients for whom the benefits of reducing the risk of VTE with heparin outweigh the increased risk of intracranial and extracranial bleeding.[135][268] There is no prediction tool to identify these patients, but patients considered to be at particularly high risk of VTE include those with complete paralysis of the leg, previous VTE, dehydration, or comorbidities (such as malignancy or sepsis), or current or recent smokers.[135][268]

Early mobilization is recommended for stroke patients, but very early, intense mobilization (e.g., multiple out-of-bed sessions) within 24 hours of stroke onset should not be performed.[135][270] Early mobilization may decrease risk of VTE by reducing venous stasis, but this has not been demonstrated in controlled trials.[268] See Venous thromboembolism prophylaxis.

presentation after 4.5 hours, or not otherwise eligible for or contraindication to intravenous thrombolysis

1st line – antiplatelet therapy

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1st line –

antiplatelet therapy

Guidelines recommend that ischemic stroke patients receive aspirin, whether or not they are eligible for intravenous thrombolysis.[135]

In patients with recent minor (National Institutes of Health Stroke Scale [NIHSS] score ≤3) noncardioembolic ischemic stroke or high-risk TIA (ABCD2 score ≥4), guidelines from the American Heart Association/American Stroke Association (AHA/ASA) recommend that dual antiplatelet therapy (aspirin plus clopidogrel) should be initiated early (ideally within 12-24 hours of symptom onset and at least within 7 days of onset) and continued for 21-90 days, followed by single antiplatelet therapy, to reduce the risk of recurrent ischemic stroke.[113][135][186][187]

The dual antiplatelet therapy regimen of ticagrelor plus aspirin is approved in the US by the Food and Drug Administration (FDA) to reduce the risk for stroke in patients with acute ischemic stroke with a NIHSS score of ≤5 or high-risk TIA. In Europe, an application to the European Medicines Agency (EMA) to change the marketing authorization of ticagrelor to include the prevention of stroke in adults who have had a mild to moderate ischemic stroke or high-risk TIA was withdrawn in December 2021. Based on trial data and the company’s response to their questions, the EMA expressed concern that the benefits of short-term treatment with ticagrelor plus aspirin in preventing stroke in these patients did not clearly outweigh the risks of fatal and nonfatal bleeding. For patients with an acute ischemic stroke and an NIHSS score of <5, the use of ticagrelor plus aspirin for 30 days reduced recurrent ischemic events in a randomized, placebo-controlled, double-blind trial. However, severe bleeding was more frequent with ticagrelor plus aspirin than with aspirin alone.[191] In Chinese patients with minor stroke and high risk-TIA (NIHSS score <3) who are carriers of CYP2C19 loss-of-function allele, the use of ticagrelor plus aspirin modestly reduced the risk of stroke at 90 days compared with clopidogrel plus aspirin. The combination treatment was for 21 days followed by either ticagrelor or clopidogrel alone for up to 90 days.[193]

Antiplatelet therapy with aspirin or clopidogrel (either alone or with patent foramen ovale [PFO] closure) is recommended for the secondary prevention of stroke in patients with cryptogenic ischemic stroke secondary to PFO.[235] All patients with previous stroke should be treated with an antithrombotic indefinitely if there is no bleeding contraindication, regardless of whether a PFO is present or if it is closed. For patients aged under 60 years, PFO closure plus antiplatelet therapy is likely to be of benefit for secondary stroke prevention compared with anticoagulant therapy.[235] PFO closure plus antiplatelet therapy is preferred to antiplatelet therapy alone if anticoagulation is contraindicated or declined.[235][240] See Patent foramen ovale.

Consult specialist or local protocols for guidance on the choice of an appropriate antiplatelet regimen and doses.

Plus – high-intensity statin

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Plus –

high-intensity statin

Treatment recommended for ALL patients in selected patient group

Primary options

atorvastatin: 40-80 mg orally once daily

Plus – supportive care

Back

Plus –

supportive care

Treatment recommended for ALL patients in selected patient group

Tracheal intubation: animated demonstration

How to insert a tracheal tube in an adult using a laryngoscope.

Bag-valve-mask ventilation: animated demonstration

How to use bag-valve-mask apparatus to deliver ventilatory support to adults. Video demonstrates the two-person technique.

Management of arterial blood pressure (BP) in acute ischemic stroke remains controversial because of conflicting evidence and a lack of large controlled clinical trials.[135] Many patients with ischemic stroke have elevated BP at presentation. Lowering BP could reduce cerebral perfusion pressure and promote stroke extension.[135][254] However, American Heart Association/American Stroke Association (AHA/ASA) guidelines recommend early treatment of hypertension when required by comorbid conditions (e.g., concomitant acute coronary event, acute heart failure, aortic dissection, postfibrinolysis, sICH [symptomatic intracerebral hemorrhage]). Management in these situations should be individualized, but in general, initial BP reduction by 15% is a reasonable goal.[135] In patients with BP of ≥220/120 mmHg who did not receive intravenous thrombolytic or endovascular treatment and have no comorbid conditions requiring acute antihypertensive treatment, it may be reasonable to lower BP by 15% during the first 24 hours after onset of stroke to improve outcomes.[135][212] In patients with BP <220/120 mmHg who do not receive intravenous thrombolysis or endovascular treatment and do not have a comorbid condition requiring emergent antihypertensive treatment, initiating or reinitiating treatment of hypertension within the first 48-72 hours after an ischemic stroke is not effective to prevent death or disability.[212] In patients who undergo endovascular thrombectomy, it is reasonable to maintain BP at ≤180/105 mmHg during and for 24 hours after the procedure to improve long-term functional outcomes and prevent death.[212] Lowering systolic BP <140 mmHg within the first 24-72 hours after reperfusion via endovascular thrombectomy can worsen long-term functional outcome.[212]

Fever may be associated with poor stroke outcome.[135][259] Treatment of fever is, therefore, reasonable, although not yet shown to be effective by controlled trials.[135][260][261][262]

Plus – swallowing assessment

Back

Plus –

swallowing assessment

Treatment recommended for ALL patients in selected patient group

A reasonable approach is to withhold oral intake if there is coughing or a wet voice after swallowing a small cup of water.

Patients who cannot take nutrition orally should receive fluids and enteral feeding by nasogastric, nasoduodenal, or percutaneous gastrostomy tube. [ ]

Consider – mechanical thrombectomy

Back

Consider –

mechanical thrombectomy

Treatment recommended for SOME patients in selected patient group

Endovascular interventions include mechanical clot-removing devices, such as stent retrievers, and intra-arterial thrombolysis. Initiation of endovascular interventions should be carried out as early as possible.[135] The American Heart Association/American Stroke Association (AHA/ASA) recommends intra-arterial thrombectomy without intravenous thrombolysis for patients who present between 4.5 and 6.0 hours after stroke onset.[135]

Subsequent evidence/research suggests patients who present 6-24 hours after stroke onset (last known normal) who meet specific eligibility criteria may also benefit from intra-arterial thrombectomy without intravenous thrombolysis.[135][178][205][206][207] The risk of complications with sequelae for patients from mechanical thrombectomy has been estimated to be around 15%; such complications need to be minimized and effectively managed to maximize the benefits of thrombectomy.[201]

The AHA/ASA guidelines suggest that patients meeting all of the following criteria can be treated with a stent retriever: have a prestroke Modified Rankin Disability Scale score 0 to 1; have causative occlusion of the internal carotid artery or proximal middle cerebral artery (M1); ages ≥18 years; have a National Institutes of Health Stroke Scale score ≥6; have an Alberta Stroke Program Early CT score (ASPECTS) ≥6; and can begin endovascular therapy (groin puncture) within 6 hours of symptom onset.[135]

Expert consensus opinion from the American College of Radiology recommends against using endovascular intervention when there is evidence of a large irreversible infarction in the territory of the index vessel since the likelihood of procedure-related harm due to reperfusion resulting in hemorrhagic transformation may be higher than in those with smaller baseline infarction.[178] However, recent data from six internationally conducted trials suggest thrombectomy may be useful in selected patients with large ischemic strokes (i.e., Alberta Stroke Program Early CT score [ASPECTS] of 0-5 on noncontrast CT or MRI-DWI).[205][206][219][221][222][223] These trials were conducted in patients ages 18-85 years with acute ischemic stroke from a large vessel occlusion and large core infarctions who received intra-arterial thrombectomy from <6 to 24 hours of onset. Results from all trials showed improved functional outcome and slightly increased intracranial hemorrhage but no difference in mortality.

Consider – anticoagulation

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Consider –

anticoagulation

Treatment recommended for SOME patients in selected patient group

See Patent foramen ovale.

Consider – VTE prophylaxis + early mobilization

Back

Consider –

VTE prophylaxis + early mobilization

Treatment recommended for SOME patients in selected patient group

Venous thromboembolism (VTE) is the cause of about 10% of stroke deaths.[267]

with cerebral venous sinus thrombosis

1st line – anticoagulation

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1st line –

anticoagulation

Treatment with anticoagulation should begin as soon as the diagnosis of cerebral venous sinus thrombosis (CVST) is confirmed.[91] Specialist guidance should be sought on whether to choose low molecular weight heparin (LMWH) or unfractionated heparin. The American Heart Association and the European Stroke Organisation preferentially suggest an LMWH over unfractionated heparin due to more practical administration, more predictable anticoagulation effect, lower risk of thrombocytopenia, efficacy of LMWH and lower rates of hemorrhagic complications.[8][162] The presence of venous hemorrhage does not constitute a contraindication for anticoagulation.[8][77][241] For subsequent prevention of CVST, the treatment duration depends on the number of episodes of CVST and if there is a known underlying cause identified. Treatment duration should be discussed with a hematologist. Oral anticoagulants used for CVST include vitamin K antagonists such as warfarin (INR range 2.0 to 3.0), and direct oral anticoagulants such as apixaban, edoxaban, rivaroxaban, or dabigatran. DOACs appear to be a safe and effective alternative option to VKAs according to open-label retrospective and prospective randomized studies.[8][242][243][244][245]

Consult local protocols for guidance on the choice of an appropriate anticoagulation regimen and doses.

Plus – supportive care

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Plus –

supportive care

Treatment recommended for ALL patients in selected patient group

Admission to a dedicated stroke unit, in comparison to admission to a general medical/surgical service, is associated with improved survival and less disability at 1 year.[263][264] [ ] Stroke units should have multidisciplinary teams, including physicians, nursing staff, and rehabilitation specialists with expertise in stroke. Improved supportive care, avoidance of complications such as infection, and earlier initiation of rehabilitation therapy are among the mechanisms by which stroke units are hypothesized to produce better outcomes.

Supplemental oxygen should be provided only when blood oxygen saturation is <94%.Liberal use of oxygen is associated with increased mortality in acutely sick patients.[248][249] Patients with decreased level of consciousness or refractory hypoxemia may require intubation with mechanical ventilation.[135][250]

Tracheal intubation: animated demonstration

How to insert a tracheal tube in an adult using a laryngoscope.

Bag-valve-mask ventilation: animated demonstration

How to use bag-valve-mask apparatus to deliver ventilatory support to adults. Video demonstrates the two-person technique.

Fever may be associated with poor stroke outcome.[135][259] Treatment of fever is, therefore, reasonable, although not yet shown to be effective by controlled trials.[135][260][261][262]

Plus – swallowing assessment

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Plus –

swallowing assessment

Treatment recommended for ALL patients in selected patient group

A reasonable approach is to withhold oral intake if there is coughing or a wet voice after swallowing a small cup of water.

Patients who cannot take nutrition orally should receive fluids and enteral feeding by nasogastric, nasoduodenal, or percutaneous gastrostomy tube. [ ]

Consider – direct thrombectomy or intra-clot thrombolysis

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Consider –

direct thrombectomy or intra-clot thrombolysis

Treatment recommended for SOME patients in selected patient group

In select cases of cerebral venous sinus thrombosis, endovascular therapies (direct thrombectomy or intra-clot thrombolysis with intravenous thrombolysis) may be considered by a multidisciplinary team.[91] Given the lack of controlled studies (and poorer outcomes in meta-analyses), endovascular therapies are reserved for patients with evidence of thrombus propagation, for individuals with neurologic deterioration despite medical therapy, or for those with contraindications to anticoagulation.[8]

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Ischemic stroke

Treatment algorithm

without cerebral venous sinus thrombosis

recombinant tissue plasminogen activator (r-tPA)

Primary options

antiplatelet therapy

high-intensity statin

Primary options

supportive care

swallowing assessment

mechanical thrombectomy

anticoagulation

VTE prophylaxis + early mobilization

antiplatelet therapy

high-intensity statin

Primary options

supportive care

swallowing assessment

mechanical thrombectomy

anticoagulation

VTE prophylaxis + early mobilization

with cerebral venous sinus thrombosis

anticoagulation

supportive care

swallowing assessment

direct thrombectomy or intra-clot thrombolysis