Approach

Rapid evaluation and diagnosis is the cornerstone of successful therapy for ischemic stroke. Prioritize stabilizing the patient by managing any airway, breathing, and circulatory insufficiencies requiring urgent treatment; continue to give supportive care as needed (see section on "Supportive care"). The goals of treatment are to:

  • Restore blood flow

  • Support energy metabolism in ischemic tissue

  • Treat complications of stroke-related edema

  • Prevent common acute medical complications.

Intravenous thrombolysis

See section on "Candidates for intravenous thrombolysis with alteplase" for recommendations on which patients are eligible for treatment with intravenous thrombolysis.

There are three intravenous formulations of recombinant tissue plasminogen activator (r-tPA) available in the US: alteplase, tenecteplase, and reteplase. Only alteplase is currently approved for use in acute ischemic stroke. The other two are approved for use in acute myocardial infarction only.

Alteplase promotes thrombolysis and thereby recanalization and reperfusion. Early administration of intravenous alteplase is recommended for appropriate patients who meet the defined criteria for thrombolysis.[119] 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.[145][146][147]​​ In a retrospective cohort study of more than 61,000 patients ages 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.[146] Administration of alteplase should not be delayed by additional tests unless a specific contraindication is suspected and must be ruled out. Blood glucose should be normalized before initiating alteplase treatment.[119] Orolingual edema is a rare but potentially serious complication.

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.

Trials of alteplase for thrombolysis in patients with acute ischemic stroke and no contraindications suggest that the ideal window of opportunity for treatment is up to 4.5 hours after the onset of neurologic symptoms.[119][148]​ For patients with severe acute stroke, goal time from emergency department arrival to initiation of intravenous alteplase (if indicated) is 60 minutes.[117][149] Alteplase is approved in the US for use within 3 hours of onset of stroke symptoms, and in Europe for use within 4.5 hours.

Tenecteplase is at least as effective and safe as alteplase.[147][150][151]​​​​[152]​ The American Heart Association/American Stroke Association (AHA/ASA) recommend to consider tenecteplase as an alternative to alteplase in patients with minor neurologic impairment and no major intracranial occlusion.[119]

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 alteplase in an otherwise eligible adult patient with a disabling ischemic stroke.[119] 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.[153]

Decision-makers should be informed that r-tPA 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.[154] Overall, 1 in 8 people treated with r-tPA have a complete or near-complete recovery who otherwise would have been disabled.[155] 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.[156]

Contraindications to intravenous thrombolysis with alteplase

The following are contraindications to alteplase treatment from the AHA/ASA guidelines:[119]

Absolute contraindications:

  • Onset of symptoms >9 hours[157]

  • CT reveals acute intracranial hemorrhage

  • History of severe head trauma

  • Symptoms suggestive of subarachnoid hemorrhage

  • Patients with platelets <100,000/mm³, international normalized ratio (INR) >1.7, activated PTT (aPTT) >40 seconds, or prothrombin time >15 seconds

  • Patient has received a dose of low-molecular-weight heparin within the previous 24 hours

  • Evidence of active bleeding on examination

  • Symptoms consistent with infective endocarditis

  • Known or suspected association between the acute ischemic stroke and aortic arch dissection

Relative contraindications:

  • History of prior stroke in the previous 3 months

  • History of previous intracranial hemorrhage

  • History of intracranial/intraspinal surgery within 3 months

  • Patient is taking antiplatelet agents that inhibit the glycoprotein IIb/IIIa receptor

  • History of an intra-axial intracranial neoplasm

  • History of gastrointestinal malignancy or recent bleeding event in the previous 21 days

  • History of major surgery or serious trauma in the previous 14 days

  • Patient is taking direct thrombin inhibitors or direct factor Xa inhibitors unless laboratory tests such as aPTT, INR, platelet count, ecarin clotting time, thrombin time, or appropriate direct factor Xa activity assays are normal or the patient has not received a dose of these agents for >48 hours (assuming normal renal metabolizing function).

Refer to your local drug formulary for contraindications to the use of tenecteplase.

Candidates for intravenous thrombolysis with alteplase

The AHA/ASA guidelines state that the eligibility recommendations for treating with alteplase are:[119]

  • Within 3 hours of stroke symptom onset or patient last known well or at baseline state:

    • Medically eligible patients aged ≥18 years (equally recommended for patients ages <80 and >80 years)

    • Patients with severe stroke symptoms or mild but disabling stroke symptoms

  • Within 3.0 to 4.5 hours of stroke symptom onset or patient last known well:

    • Patients aged ≤80 years

    • 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

  • Patients whose blood pressure can be lowered safely to <185/110 mmHg with antihypertensive agents

  • Patients 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.

Additional recommendations for treatment with alteplase can be found in the AHA/ASA guidelines.[119]

Normalizing blood glucose

Glucose levels must be >50 mg/dL before initiating intravenous alteplase treatment. For more information, see section on "Supportive care" below.

Lowering blood pressure

Blood pressure must be <185/110 mmHg before initiating intravenous alteplase treatment.[119] For more information, see section on "Supportive care" below.

Patients with major deficits and older patients

When treating a patient with major deficits, the likelihood of favorable outcome is reduced and there is increased risk of hemorrhage following thrombolysis.[119] The AHA/ASA guidelines state that for otherwise medically eligible patients ≥18 years of age, alteplase administration within 3 hours is equally recommended for patients ≤80 and >80 years of age.[119][158] Although use of alteplase has previously been restricted to people aged under 80 years, evidence shows that patients aged over 80 years derive as much benefit (reduced death or dependency, improved functional outcomes) from alteplase as do those aged under 80 years, especially if treated within 3 hours of stroke.[145][159][160]

Aspirin and dual antiplatelet therapy

Guidelines recommend that ischemic stroke patients receive aspirin, whether or not they are eligible for alteplase.[119] However, if alteplase is given, aspirin should not be started for 24 hours, and only then after a head CT shows the absence of intracranial hemorrhage.[119][161]

Early (i.e., within 24 hours) administration of aspirin in acute ischemic stroke patients receiving alteplase did not show any significant improvements in outcomes at 3 months.[161]

Patients with minor stroke

For patients with noncardioembolic ischemic stroke or transient ischemic attack (TIA), guidelines from the AHA/ASA recommend aspirin, clopidogrel, or the combination of aspirin plus extended-release dipyridamole for secondary prevention of ischemic stroke.[102] 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 to 90 days, followed by single antiplatelet therapy, to reduce the risk of recurrent ischemic stroke.[102][119][162][163] The dual antiplatelet therapy regimen of ticagrelor plus aspirin is approved by the Food and Drug Administration (FDA) in the US 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 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.

Evidence supporting dual antiplatelet therapy

One meta-analysis found that dual antiplatelet therapy with clopidogrel plus aspirin within 24 hours after minor ischemic stroke (NIHSS score of ≤3; patients not candidates for intravenous thrombolysis) or high-risk TIA reduced the absolute risk of subsequent stroke by 2% compared with aspirin alone.[164] All-cause mortality did not differ between treatment groups; clopidogrel plus aspirin was associated with a small absolute increased risk of moderate or severe extracranial bleeding (0.2%).[164] In a second meta-analysis, the risk of recurrent ischemic stroke in patients with acute ischemic stroke or TIA was significantly reduced with short-term (≤1 month; RR 0.53, 95% CI 0.37 to 0.78) and intermediate-term (≤3 months; RR 0.72, 95% CI 0.58 to 0.90) aspirin plus clopidogrel compared with aspirin alone, but long-term combination treatment (>3 months) did not reduce risk of recurrent ischemic stroke (RR 0.81, 95% CI 0.63 to 1.04).[165] Intermediate-term (RR 2.58, 95% CI 1.19 to 5.60) and long-term (RR 1.87, 95% CI 1.36 to 2.56) combined treatment significantly increased the risk of major bleeding, but short-term treatment did not (RR 1.82, 95% CI 0.91 to 3.62).[165]

The THALES trial of 11,016 patients (none of whom received thrombolysis or thrombectomy or required anticoagulation) demonstrated that compared with aspirin alone, dual treatment with ticagrelor plus aspirin reduced the risk of disabling stroke or death within 30 days (4.0% vs. 4.7%).[166] Severe bleeding was more frequent with ticagrelor plus aspirin than with aspirin alone (0.5% vs. 0.1%), including intracranial hemorrhage (0.4% vs. 0.1%). For patients with recent stroke with an NIHSS score of <5, ticagrelor plus aspirin for 30 days was more effective in preventing recurrent ischemic stroke than aspirin alone.[166]

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.[166]

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.[167]

Endovascular interventions

As with alteplase, initiation of endovascular interventions should be carried out as early as possible.[119] Intravenous thrombolysis with alteplase 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.[119][168][169][170] Clinical trials and registry data have proven the efficacy of this approach.[171][172][173][174]

The role of thrombectomy alone without intravenous thrombolysis (e.g., where there are contraindications for thrombolysis) has not yet been ascertained. Intra-arterial thrombectomy may be considered without intravenous thrombolysis for:

  • Patients who present between 4.5 and 6.0 hours after stroke onset[119]

  • Patients who present 6-24 hours after stroke onset (last known normal) who meet specific eligibility criteria.[119]

Endovascular interventions include mechanical clot-removing devices, such as stent retrievers, and intra-arterial thrombolysis. The AHA/ASA guidelines 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.[119] The use of a proximal balloon guide catheter or 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.[119] Furthermore, it may be reasonable to use an adjunctive intervention (e.g., intra-arterial thrombolysis) to achieve acceptable reperfusion, if used within 6 hours of symptom onset.

One systematic review found that, even in patients with mild strokes due to LVO who were not eligible for intravenous thrombolysis with alteplase, mechanical thrombectomy resulted in better 90-day functional outcomes, and suggested that this treatment can play an important role for patients not eligible for intravenous alteplase.[175] Analysis from three randomized controlled clinical trials (1,092 patients) detected no differences in functional outcomes of intravenous thrombolysis-eligible patients with an acute LVO receiving direct endovascular treatment compared with endovascular treatment preceded by intravenous thrombolysis.[176] The authors noted that because uncertainty for most endpoints remains large and the available data are not able to exclude the possibility of overall benefit or harm, further randomized controlled trials are needed.[176] A subsequent randomized trial (539 patients) found that endovascular treatment alone was neither superior nor noninferior to intravenous alteplase followed by direct endovascular treatment with regard to disability outcome at 90 days after stroke with no difference in the rate of hemorrhage.[177]

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.[178]

General anesthesia during endovascular thrombectomy is associated with worse patient outcomes compared with no general anesthesia (with or without sedation).[179]

Candidates for endovascular interventions

The 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.[119] Observing patients for a clinical response to intravenous alteplase prior to use of endovascular therapy should not be performed.[119]

The AHA/ASA guidelines suggest that patients who meet all of the following criteria should be treated with a stent retriever:[119]

  • Have a prestroke Modified Rankin Disability Scale score 0-1

  • Have causative occlusion of the internal carotid artery or proximal middle cerebral artery (M1)

  • Aged ≥18 years

  • Have an NIHSS score ≥6

  • Have an Alberta Stroke Program Early CT score (ASPECTS) ≥6

  • Can begin endovascular therapy (groin puncture) within 6 hours of symptom onset.

Although there is a lack of evidence for stent retrievers in ischemic stroke patients outside these criteria, they may be considered for use in patients with anterior circulation arterial occlusion who cannot be treated with intravenous thrombolysis, or patients with occlusion of other vessels, such as the M2 or M3 portion of the middle cerebral artery, anterior cerebral arteries, vertebral arteries, basilar artery, or posterior cerebral arteries. They may also be considered for patients who are aged <18 years, or have a Modified Rankin Disability Scale score >1, or an ASPECTS <6, if initiated within 6 hours of symptom onset, but the potential benefits are unclear as there is a lack of evidence in these patients.[119]

Regarding thrombectomy, AHA/ASA guidelines state:[119]

  • Thrombectomy is recommended within 6-16 hours of "last known well" in selected patients with acute ischemic stroke who have LVO in the anterior circulation and who meet other DAWN or DEFUSE 3 eligibility criteria (see table)

  • Thrombectomy is reasonable within 16-24 hours of last known well in selected patients with acute ischemic stroke who have LVO in the anterior circulation and who meet other DAWN eligibility criteria (see table).

The DAWN trial used clinical imaging mismatch (combination of NIHSS score and imaging findings on CT perfusion or diffusion-weighted MRI) as eligibility criteria to select patients with LVO in the anterior circulation for mechanical thrombectomy 6-24 hours from last known well.[180]

The DEFUSE 3 trial used perfusion-core mismatch and maximum core size as imaging criteria to select patients with LVO in the anterior circulation for mechanical thrombectomy 6-16 hours from last known well.[181]

For patients who otherwise meet criteria for mechanical thrombectomy, noninvasive vessel imaging of the intracranial arteries is recommended during the initial imaging evaluation.[119] An appropriate penumbra on CT perfusion or magnetic resonance perfusion imaging is essential before thrombectomy.

Initial treatment with intra-arterial thrombolysis may be considered for carefully selected patients with major ischemic strokes of <6 hours' duration with causative occlusion of the anterior circulation, including the anterior cerebral artery, middle cerebral artery, or distal internal carotid artery, or those with contraindications or an incomplete response to intravenous thrombolysis.[182] However, the evidence for effectiveness is weak, and there are no intra-arterial thrombolytic interventions approved for use in stroke.

[Figure caption and citation for the preceding image starts]: Data from DAWN and DEFUSE-3 trials (cerebral blood flow [CBF]; time-to-maximum [Tmax]; internal carotid artery [ICA]; middle cerebral artery [MCA])Created by BMJ Knowledge Centre using data from Dawn-Nogueira et al. N Engl J Med. 2018 378(1):11-21 and Defuse-Albers et al. N Engl J Med. 2018 22;378(8):708-18 [Citation ends].com.bmj.content.model.Caption@3e931542

Anticoagulation

Urgent anticoagulation in unselected ischemic stroke patients, with the goal of improving acute stroke outcomes, is generally not recommended.[119] Meta-analyses failed to show a reduction in stroke disability in acute ischemic stroke patients treated with anticoagulants, but do show an increase in the risk of hemorrhagic transformation of stroke, particularly in patients with larger stroke volumes.[183] [ Cochrane Clinical Answers logo ] [Evidence A]​

Although one trial did not find a significant benefit of low-molecular-weight heparin (LMWH) over aspirin in patients with large artery occlusive disease, subgroup analyses and an unblinded randomized controlled trial suggest that LMWH may prevent early neurologic deterioration in subgroups of patients such as older patients and patients with symptomatic posterior circulation arterial disease.[184][185]

Patients with atrial fibrillation

The optimal time for initiating anticoagulation in patients with atrial fibrillation after acute ischemic stroke or TIA is unclear. The AHA/ASA guidelines recommend starting oral anticoagulation 4 to 14 days after stroke symptom onset.[119] 

In patients with nonvalvular atrial fibrillation and stroke or TIA, oral anticoagulation (e.g., apixaban, edoxaban, rivaroxaban, dabigatran, or warfarin) is recommended to reduce the risk of recurrent stroke, regardless of whether the atrial fibrillation pattern is paroxysmal, persistent, or permanent.[102] Direct-acting oral anticoagulants (DOACs) such as apixaban, edoxaban, rivaroxaban, or dabigatran are recommended over warfarin in patients with stroke or TIA and atrial fibrillation who do not have moderate to severe mitral stenosis or a mechanical heart valve.[102] Large randomized trials have shown DOACs to clinically reduce the risk of thrombotic stroke with less bleeding risk compared with vitamin K antagonists (e.g., warfarin).[102]

The international normalized ratio (INR) range for patients on warfarin is 2.0 to 3.0.[102][186] A validated scoring system should be used to assess the bleeding risk of the patient; if high, the patient should be followed up more closely.[187][188] See New-onset atrial fibrillation.

Stroke or TIA with stenosis of a major intracranial artery

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][102]

In patients with 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][102]

In patients with minor stroke or high-risk TIA within 24 hours 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.[102] The dual antiplatelet therapy regimen of ticagrelor plus aspirin is approved in the US by the 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 EMA to change the marketing authorization of ticagrelor to include the prevention of stroke in adults who have had 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.

Carotid endarterectomy (CEA) and carotid artery stenting (CAS)

In patients with symptomatic carotid stenosis (i.e., TIA or nondisabling stroke) within the past 6 months and ipsilateral severe (70% to 99%) carotid artery stenosis, CEA is recommended to reduce the risk of future stroke. This is appropriate only if perioperative morbidity and mortality risk is estimated to be <6%.[102]

In patients younger than 68 years and with symptomatic carotid stenosis (i.e., TIA or nondisabling stroke), CAS is preferred over CEA if the degree of stenosis is between 50% and 69% (as determined by digital subtraction angiography). This is appropriate only if perioperative risk of morbidity and mortality is <6%. CEA or CAS is beneficial for patients with 70% to 99% stenosis without near-occlusion. No evidence of benefit has been found in patients with a stenosis of <50% or near-occlusion.[45][46][189]

In patients older than 68 years and with TIA or ischemic stroke and ipsilateral moderate (50% to 69%) carotid stenosis (as documented by catheter-based imaging or noninvasive imaging), CEA is recommended to reduce the risk of future stroke. This is appropriate only if perioperative morbidity and mortality risk is <6%. Patient-specific factors such as age, sex, and comorbidities will also affect the suitability of CEA.[102]

CEA and CAS showed similar benefits in stroke prevention in one randomized controlled trial. Stenting tended to be more effective in patients younger than 68 years, whereas endarterectomy tended to be more effective those in older than 68 years. Stenting was associated with slightly more strokes, and endarterectomy was associated with slightly more myocardial infarctions and 12th cranial nerve damage.[190] The durability of carotid artery stenting was proven at 10-year follow-up; survival rate was slightly lower in the stenting group than in the endarterectomy group (probably due to periprocedural differences in risk).[191]

See Carotid artery stenosis.

Patent foramen ovale (PFO)

PFO closure (with antiplatelet therapy), antiplatelet therapy alone, or anticoagulants alone are options for the secondary prevention of stroke in patients with cryptogenic ischemic stroke secondary to PFO.[192] Antiplatelet options include aspirin or clopidogrel.[193] In patients with a high risk of paradoxical embolism (RoPE) score, closure of the PFO reduces stroke recurrence compared with medical treatment alone.[194][195][196][197][198]

In patients younger than 60 years with a PFO and embolic-appearing infarct and no other mechanism of stroke identified, clinicians may recommend closure. This decision should always include a discussion of potential benefits (absolute recurrent stroke risk reduction of 3.4% at 5 years) and risks (periprocedural complication rate of 3.9% and increased absolute rate of non-periprocedural atrial fibrillation of 0.33% per year).[192]

PFO closure may be considered in other populations, such as for a patient who is aged 60-65 years with a very limited degree of traditional vascular risk factors (i.e., hypertension, diabetes, hyperlipidemia, or smoking) and no other mechanism of stroke detected following a thorough evaluation, including prolonged monitoring for atrial fibrillation.[192]

All patients with previous stroke should be treated with an antithrombotic medication 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.[193] PFO closure plus antiplatelet therapy is preferred to antiplatelet therapy alone if anticoagulation is contraindicated or declined.[193][199]

Atrial fibrillation is more frequent in patients who have their PFO closed, but is mostly transient.[197] [199]

See Patent foramen ovale.

Patients with cerebral venous sinus thrombosis (CVST)

CVST can cause intracerebral venous hemorrhage, ischemic stroke, brain edema, midline shift, and elevation of intracranial pressure. Treatment with anticoagulation should begin as soon as the diagnosis of CVST is confirmed.[8][83]​​​​​ Specialist guidance should be sought on whether to choose low molecular weight heparin (LMWH) or unfractionated heparin. The American Heart Association and European Stroke Organisation preferentially suggest an LMWH over unfractionated heparin due to the more practical administration, more predictable anticoagulation effect, lower risk of thrombocytopenia, efficacy of LMWH and lower rates of hemorrhagic complications.[8][144]​​​​​​​ The presence of venous hemorrhage does not constitute a contraindication for anticoagulation.[8][200][201]​​​ 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 DOACs. DOACs appear to be a safe and effective alternative option to VKAs according to open-label retrospective and prospective randomized studies.[8][202][203][204][205]​​ In select cases of CVST, endovascular therapies (direct thrombectomy or intra-clot thrombolysis with r-tPA) may be considered by a multidisciplinary team.[83] 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]​​

Statins

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.[102][206] Statin treatment should not be started immediately. There is consensus that it is safe to start statins after 48 hours.[133] Statin treatment should be continued in people who are already receiving statins.[133]

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][207] 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.[102]

  • In patients with stroke or TIA and hyperlipidemia, adherence to changes in lifestyle and the effects of LDL-C–lowering medication 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.[102]

Supportive care

At the same time as acute evaluation for thrombolysis and/or thrombectomy, the following steps should be taken:

  • Support blood oxygenation. 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.[208][209] Patients with decreased level of consciousness or refractory hypoxemia may require intubation with mechanical ventilation.[119][210]

    Tracheal intubation: animated demonstration
    Tracheal intubation: animated demonstration

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

    Bag-valve-mask ventilation: animated demonstration
    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.

  • Support systemic blood pressure. Management of arterial blood pressure in acute ischemic stroke is controversial because of conflicting evidence and a lack of large controlled clinical trials.[119] Many patients with ischemic stroke have elevated blood pressure at presentation. Lowering blood pressure could reduce cerebral perfusion pressure and promote stroke extension.[119][214] However, AHA/ASA guidelines recommend early treatment of hypertension when required by comorbid conditions. Particular comorbidities include concomitant acute coronary event, acute heart failure, aortic dissection, post-fibrinolysis sICH [symptomatic intracerebral hemorrhage], or preeclampsia/eclampsia. Management of these patients should be individualized, but in general, initial blood pressure reduction by 15% is a reasonable goal.[119] Blood pressure of <185/110 mmHg is required before initiating intravenous alteplase. Intensive lowering of systolic blood pressure to 130-140 mmHg within 1 hour before alteplase treatment was found to be safe, but it did not appear to improve clinical outcomes compared with a target of <180 mmHg.[215][216]

  • Normalize blood glucose levels (required before initiating intravenous alteplase).

    • 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 an intravenous insulin drip 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%).[217] Hypoglycemia can be well controlled with frequent subcutaneous insulin injections based on a sliding scale.[218]

    • Hyperglycemia has been associated with poor outcome and risk of hemorrhagic transformation of ischemic stroke.[119][139][140][141] 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.[119]

  • Reduce fever. Fever may be associated with poor stroke outcome.[119][219] Treatment of fever is therefore reasonable, although not yet shown to be effective by controlled trials.[119][220][221][222]

These steps, while not shown to be effective in clinical trials, may retard stroke evolution or prevent stroke extension by optimizing energy substrate delivery and tissue energy metabolism.

Following emergency department evaluation and treatment, patients with ischemic stroke should be transferred to a dedicated stroke unit. These units improve stroke functional outcome and survival.[119][223][224]​​ [ Cochrane Clinical Answers logo ] ​​ Stroke units should have multidisciplinary teams which include 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.

Nutritional support, rehabilitation therapy (physical, occupational, and/or speech therapy as indicated), prevention of aspiration (swallowing assessment), and prevention of deep vein thrombosis (DVT)/venous thromboembolism (VTE) are all required in the subacute phase of hospital care. [ Cochrane Clinical Answers logo ] [ Cochrane Clinical Answers logo ]

Swallowing impairment is common in stroke and is associated with an increased risk of aspiration pneumonia and death.[225][226] Guidelines support the use of a bedside swallow test before eating or drinking but do not provide specifics on test administration and interpretation.[119] 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 isotonic fluids (to decrease risk of brain edema) and have enteral feeding by nasogastric, nasoduodenal, or percutaneous gastrostomy tube. [ Cochrane Clinical Answers logo ]

VTE prophylaxis

VTE is the cause of about 10% of stroke deaths.[227]

Intermittent pneumatic compression of the legs is recommended to reduce the risk of DVT/VTE in nonambulatory stroke patients.[119][228][229] Elastic compression stockings are not recommended.[119][228]

The benefits of prophylactic subcutaneous heparin in patients with acute ischemic stroke are not well established; it decreases the rates 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.[119] Guidelines note that there may be a subgroup of patients for whom the benefits of reducing the risk of VTE with heparin outweighs the increased risk of intracranial and extracranial bleeding.[119][228] 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.[119][228]

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.[119][230] Early mobilization may decrease risk of VTE by reducing venous stasis, but this has not been demonstrated in controlled trials.[228]

See Venous thromboembolism prophylaxis.

Rehabilitation

Early rehabilitation after stroke is recommended.[231] However, high intensity, very early mobilization within 24 hours of stroke onset should not be performed because it can reduce the odds of a favorable outcome at 3 months.[119]

  • Because of neurologic injury, many stroke patients have limited ambulation and mobility, which reduces quality of life.

  • The objective of rehabilitation is to enable the person to return to an acceptable social and/or working life.

Speech and language therapy is crucial in order to increase the degree of functional communication. About one third of patients who have a stroke develop aphasia.[232] Differences in functional outcome when comparing specific therapy regimens (i.e., intensity, dosage, and duration) are being investigated. It is known that people who have highly intensive treatments have a higher incidence of dropping out of therapy early.[233] Mental practice describes a training method that uses cognitive rehearsal of activities to improve performance of those activities; an individual repeatedly mentally rehearses an action or task in their imagination (e.g., picking up a cup or reaching out with their arm) without physically performing the action or task. Randomized controlled trials support the use of mental practice, in addition to conventional physical rehabilitation treatment, in improving upper extremity impairment after stroke.[234]

Virtual reality and interactive video gaming have emerged as novel treatment approaches in stroke rehabilitation. One meta-analysis found that virtual reality may improve upper limb function and activities of daily living when used as an adjunct to usual care (to increase overall therapy time); however, virtual reality and interactive video gaming was not more beneficial than conventional therapy. There was insufficient evidence to reach conclusions about the effect of virtual reality and interactive video gaming on gait speed, balance, participation, or quality of life.[235] Gait Exercise Assist Robot (GEAR) may produce clinically significant improvements in balance and lower extremity function in patients with infratentorial stroke.[236]

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