Overview
Stroke Systems of Care and Prehospital Management
Emergency Evaluation and Treatment
General Supportive Early Management
In-Hospital Management of AIS: General Supportive Care
In-Hospital Management of AIS: Treatment of Acute Complications
Design and created by Guideline Central in participation with the American Heart Association and American Stroke Association.
Early Management of Patients With Acute Ischemic Stroke
American Heart Association
American Stroke Association
Publication Date: January 27, 2026
Overview
Top Take-Home Messages
- Mobile stroke units (MSU) enable rapid identification and treatment of thrombolytic-eligible patients with acute ischemic stroke (AIS). Recent studies have highlighted the benefit of MSUs over conventional emergency medical services and, when available, the guideline now includes recommendations related to the implementation of MSUs, based on their safety and benefit.
- Identification of appropriate transport destination for patients with suspected stroke in the prehospital setting remains challenging. Previous guidelines recommended transport to the nearest thrombolytic-capable facility. Given recent evidence, this guideline endorses consideration of the characteristics of the local system of care and direct transport to the closest EVT-capable hospital in the absence of well-functioning systems with rapid interhospital transfer processes.
- Intravenous thrombolysis (IVT) is a mainstay of medical management for patients with AIS. Given numerous international trials showing noninferiority and the potential advantages of intravenous tenecteplase compared with alteplase, the new guidelines endorse the use of either alteplase or tenecteplase in the 4.5-hour thrombolytic treatment window. Furthermore, we emphasize rapid thrombolytic treatment in eligible patients with disabling deficits, regardless of National Institutes of Health Stroke Scale (NIHSS) score, within the 4.5-hour window without advanced imaging selection. In addition, the guidelines provide support for extended window thrombolysis for select patients with stroke of unknown onset or 4.5–9 hours from onset using advanced imaging criteria (eg, diffusion weighted imaging-fluid attenuated recovery or perfusion-based mismatch).
- For patients with non-disabling (eg, isolated sensory syndrome) deficits in the 4.5-hour window, trials have failed to demonstrate benefit of thrombolysis. Dual antiplatelet therapy is preferred and recommended in this population.
- New studies have examined the role of adjuvant antithrombotic therapy, such as argatroban and eptifibatide, concurrently with IVT. These studies have shown no benefit and, therefore, adjuvant antithrombotic drugs are not recommended to enhance the outcomes from thrombolytic therapy.
- EVT has been established as a standard treatment for patients with AIS with large vessel occlusion (LVO) based on numerous randomized controlled trials. Recent evidence supports expanding EVT to populations previously considered ineligible. Specifically, several studies indicate that EVT benefits some patients with larger ischemic core strokes as determined by diagnostic imaging.
- Based on several trials showing improvement in functional outcomes compared with medical management alone, the guidelines also provide a strong recommendation for EVT in patients with basilar artery occlusion presenting within 24 hours of symptom onset and NIHSS score ≥10.
- For the first time, the guidelines include recommendations for interventional treatment in pediatric patients with AIS. Although much work remains to adapt prehospital and hospital stroke protocols for pediatric patients, expert consensus and recent studies highlight the importance of early stroke recognition in children and support the safety and potential benefit of endovascular interventions in select pediatric patients with AIS. These recommendations serve as a foundation for future recommendations and address the phases of pediatric acute stroke care.
- Glycemic management in patients with AIS has been updated since the prior guidelines such that intensive glucose control to the range of 80 to 130 mg/dL is not recommended to improve clinical outcome and increases the risk of severe hypoglycemia.
- Several new trials have assessed the efficacy and safety of blood pressure (BP) lowering after IVT and EVT in adult patients, providing new evidence that more intensive BP reduction does not improve functional outcome after IVT and may result in harm after EVT. Therefore, intensive systolic BP lowering to <140 mm Hg is not recommended even in the setting of complete reperfusion (eg, Thrombolysis In Cerebral Infarction grade 3 flow)
Figure 1. Journey of a Patient With AIS*
* The phases of care and key management steps and treatments are highlighted to ensure the most optimal functional outcome.
AIS indicates acute ischemic stroke; EMS, emergency medical services; EVT, endovascular thrombectomy; MSU, mobile stroke unit; and TNK, tenecteplase.
Stroke Systems of Care and Prehospital Management
Note: The numbering of the following tables may differ from that of the Clinical Practice Guideline.
Colors in tables and figures correspond to Class of Recommendations and Level of Evidence tables.
Colors in tables and figures correspond to Class of Recommendations and Level of Evidence tables.
2.1. Stroke Awareness (Population Level)
1. For the general public, implementation of educational programs on stroke recognition in patients of all ages and the need to seek emergency care (calling 9-1-1) is recommended and should be implemented by public health and community leaders and medical professionals to reduce gaps in knowledge about stroke warning signs and to improve stroke preparedness. ( 1, B-R )
2. For the general public, educational programs on stroke recognition should be designed to reach diverse communities and populations (ie, diversity by age, race and ethnicity, sex and gender, and other social determinants of health such as education, income, and neighborhood) to reduce knowledge gaps in stroke warning signs and improve stroke preparedness across all demographics. ( 1, B-NR )
3. For the general public, educational programs on stroke recognition should be sustained over time to improve long-term knowledge of stroke warning signs and stroke preparedness. ( 1, B-NR )
4. In addition to the general public, emergency medical services (EMS) professionals, physicians (including primary care professionals), and other health care personnel should receive targeted stroke educational programs to reduce prehospital delays and maximize eligibility for acute treatment of ischemic stroke (eg, thrombolysis). ( 1, B-NR )
Note: "New and of High Impact" indicates new and practice-changing recommendations since the last iteration of the guideline; not a comprehensive list of all updates.
2.2. EMS Systems
1. Health care policy makers should establish regional systems of stroke care to increase access to time-sensitive therapies that include the determination of: a) health care facilities that provide initial emergency care, including administration of IVT, and b) centers capable of performing endovascular stroke treatment with comprehensive periprocedural care to which rapid transport must be arranged when appropriate. ( 1, B-NR )
2. EMS leaders, together with local experts, regional or state agencies, and medical authorities, should develop prehospital triage protocols to ensure that patients with suspected stroke are rapidly identified, assessed with a validated tool for stroke screening, and preferentially transported to the most appropriate stroke centers. ( 1, B-NR )
3. Monitoring and feedback on quality metrics related to prehospital care can be useful to reduce delays from symptom onset to ischemic stroke reperfusion treatment and increase the odds of discharge to home. ( 2a, B-NR )
2.3. Prehospital Assessment and Management
Dispatch
1. In callers to 9-1-1, EMS dispatch use of a telephone stroke assessment tool is reasonable and can be beneficial in early identification of stroke, reduced on-scene time, and/or prioritization of transport. ( 2a, B-NR )
Ambulance transport
2. In patients with suspected stroke transported by ambulance, use of a brief stroke assessment tool by prehospital personnel is recommended to improve early stroke identification, including large vessel occlusion (LVO) stroke. ( 1, A )
3. In patients with suspected stroke transported by ambulance, prehospital personnel should provide advance notification to the receiving hospital of an inbound suspected stroke to reduce in-hospital evaluation times, increase thrombolytic use, and decrease mortality. ( 1, B-NR )
4. In patients with suspected stroke transported by ambulance, ambulance-initiated remote ischemic conditioning (RIC) with arm blood pressure (BP) cuff inflation does not improve functional outcome and is not recommended. ( 3 - No Benefit, B-R )
5. In patients with suspected stroke transported by ambulance, prehospital initiation of stroke treatment with transdermal glyceryl trinitrate (GTN, nitroglycerin) does not improve functional outcome and is potentially harmful. ( 3 - Harm, A )
6. In patients with suspected stroke transported by ambulance, intensive BP control in the field to a target of 130 to140 mm Hg systolic does not improve functional outcome. ( 3 - No Benefit, B-R )
7. (New and of High Impact) In pediatric patients with suspected stroke transported by ambulance, the usefulness of common adult stroke screening tools is uncertain because they perform poorly for identification of stroke. Newer pediatric stroke screening tools demonstrate good interrater reliability; however, their sensitivity, specificity, and predictive value in the prehospital setting remain to be determined, and their usefulness is unknown. ( 2b, B-NR )
2.4. EMS Destination Management
General Principles
1. In patients with suspected acute stroke, EMS professionals should prioritize transport to the closest appropriate facility (acute stroke-ready hospital [ASRH], primary stroke center [PSC], thrombectomy-capable stroke center [TSC], or comprehensive stroke center [CSC]) to reduce time to treatment compared with transport to a nonstroke capable hospital. ( 1, B-NR )
Areas With Local Access to Thrombectomy-Capable Stroke Center(s)
2. In patients identified by EMS professionals as having a suspected LVO stroke, direct transport to a TSC can be beneficial to increase EVT rates and reduce time to treatment compared with initial transport to a non-TSC with secondary hospital-to-hospital transfer. ( 2a, B-NR )
Areas Without Local Access to Thrombectomy-Capable Stroke Center(s)
3. In areas without well-coordinated stroke systems of care (SSOC) and local hospital(s) proficient in thrombolysis delivery and secondary interhospital transfer, it may be reasonable for EMS professionals to consider direct transport of suspected LVO patients to the closest appropriate TSC (if transport will not disqualify the patient from IVT) to increase rates of EVT and reduce time to treatment, compared with initial transport to a local stroke center with secondary hospital-to-hospital transfer for treatment. ( 2b, B-NR )
4. In areas with well-coordinated SSOC and local hospital(s) proficient in thrombolysis delivery and secondary interhospital transfer, direct transport of patients with suspected LVO to a distant (eg, 45–60 min) TSC compared with transport to a local stroke center does not improve 3-month clinical outcomes. ( 3 - No Benefit, B-R )
Interhospital Transfer
5. Hospitals and EMS professionals should establish agreements and protocols to prioritize interhospital transfer of patients with acute stroke needing a higher level of care to reduce door-in-door-out (DIDO) times. ( 1, B-NR )
2.5. Role of Mobile Stroke Units
1. In patients with suspected AIS, the use of MSUs over conventional EMS where available is recommended for the transport and management of thrombolytic-eligible patients to ensure the fastest achievable onset-to-treatment time and improve functional outcomes. ( 1, A )
2. In patients with suspected acute stroke, MSUs must be equipped to diagnose and treat patients with IVT. ( 1, A )
3. In patients with suspected acute stroke, MSU care, including streamlined protocols and use of neurological expertise, either in-person or remote telemedicine consultation, is beneficial for emergent evaluation and treatment of patient symptoms without safety concerns. ( 1, B-R )
4. In endovascular thrombectomy-eligible patients, use of MSUs can be beneficial to identify and triage patients to the appropriate thrombectomy-capable facility with prehospital notification of receiving stroke teams. ( 2a, B-NR )
2.6. Hospital Stroke Capabilities
1. In hospitals caring for patients with AIS, certification as a stroke specialty hospital certified by an external health care credentialing agency that uses national evidence-based standard criteria is recommended. ( 1, B-NR )
2.7. Emergency Evaluation of Patients With Suspected Stroke (Including ED and Stroke Teams)
1. Patients of all ages, including pediatric patients, with acute neurological deficits should benefit from an organized protocol for the emergent evaluation of their symptoms in terms of early recognition and treatment. ( 1, B-NR )
2. In pediatric patients with sudden onset and ongoing focal neurological deficits, including first-time seizure, acute stroke should be suspected to provide timely diagnosis. ( 1, C-EO )
3. Patients with suspected stroke should benefit from designation of an acute stroke team, including clinicians, nurses, and laboratory/radiology personnel to ensure careful clinical assessment, including neurological examination. ( 1, B-NR )
4. Patients with suspected stroke should benefit from the development and education of multidisciplinary stroke teams with access to stroke expertise to safely increase the rate of IVT treatment. ( 1, A )
5. Thrombolytic-eligible patients and EVT-eligible patients should benefit from stroke teams to ensure the fastest achievable onset-to-treatment time and best clinical outcomes. ( 1, A )
2.8. Telemedicine
Prehospital Telemedicine
1. For patients with suspected stroke in the prehospital setting, telemedicine in the ambulance should be considered, when feasible, to complement paramedic assessment to identify candidates for reperfusion interventions. ( 1, B-R )
Teleradiology
2. For patients with AIS presenting to EDs without in-house imaging interpretation expertise, teleradiology systems are recommended for timely review of brain imaging, identification of contraindications to thrombolysis, and facilitation of IVT decision-making. ( 1, B-NR )
Telestroke for Thrombolytic Decision-Making and Administration
3. For patients with AIS presenting to EDs without acute neurological expertise, telestroke systems are effective over usual care by the ED team for IVT decision-making and optimal thrombolytic delivery including increased thrombolytic administration and shorter time to delivery. ( 1, B-R )
4. For patients with AIS treated at hospitals without local stroke expertise, telestroke is reasonable to reduce short-term mortality. ( 2a, B-NR )
5. For patients with AIS treated at hospitals without in-house stroke expertise or telestroke capabilities, decision-making support by telephone consultation with a stroke specialist can be beneficial for IVT decision-making and consideration of EVT eligibility. ( 2a, C-LD )
Telestroke in Stroke Systems of Care
6. Health care institutions, government payers, and vendors should support the use of telemedicine/telestroke resources and systems to ensure adequate 24-hour/day and 7-day/week coverage and care of patients with AIS in a variety of settings. ( 1, C-EO )
7. For patients with AIS presenting to hospitals with telestroke capability, use of telestroke may be reasonable for triage of patients who may be eligible for appropriate interfacility transfer for emergency EVT versus local care. ( 2b, B-NR )
2.9. Organization and Integration of Components
1. Hospitals should participate in an accountable SSOC that consists of an integrated network of certified hospitals (ie, ASRH, PSC, TSC, CSC) and prehospital EMS systems designed so patients in need of acute stroke care receive appropriate and timely evaluation, diagnosis, treatment, and interhospital transfer (when appropriate) that optimizes their long-term outcomes. ( 1, C-EO )
2. Hospitals caring for patients with acute stroke that do not provide 24/7 thrombectomy treatment (eg, ASRH, PSC hospitals) should develop interhospital transfer protocols and procedures to ensure fast, safe, and efficient transfer of patients who are potentially eligible for EVT. ( 1, C-EO )
3. PSC hospitals caring for patients with acute stroke that do not provide 24/7 thrombectomy treatment and therefore rely on interhospital patient transfers should have the capability to rapidly perform and interpret intracranial vascular imaging (CTA or magnetic resonance angiography [MRA]) to identify patients with LVO eligible for EVT. ( 1, B-NR )
4. Hospitals caring for patients with acute stroke should develop and adopt care protocols that reflect current clinical guidelines as established by national and international professional organizations or state or federal agencies and laws. ( 1, B-NR )
5. (New and of High Impact) Hospitals caring for patients with acute stroke that provide EVT (ie, TSC, CSC hospitals) should develop a system to comprehensively track key time metrics and other care processes relevant to thrombectomy (eg, door-to-puncture time, successful reperfusion), as well as long-term patient outcomes. ( 1, B-R )
6. (New and of High Impact) Hospitals caring for patients with acute stroke that provide EVT (ie, TSC, CSC hospitals) should credential neurointerventionalists using established and agreed upon training and certification standards. ( 1, C-EO )
ASRH caring for patients with acute stroke that rely on interhospital patient transfers can consider having the capability to rapidly perform and interpret intracranial vascular imaging (CTA or MRA) to identify patients with LVO eligible for EVT. ( 2a, B-NR )
8. Depending on the characteristics of the local and regional systems of care, individual SSOC may consider developing mobile intervention teams to improve timely delivery of EVT. ( 2b, B-NR )
2.10. Stroke Registries, Quality Improvement, and Risk Adjustment
1. Hospitals treating patients with acute stroke should engage in a multicomponent QI process that involves the continuous monitoring, review, and feedback of stroke quality indicators, benchmarks, and evidence-based practices, in order to increase quality of care, improve patient outcomes, and reduce health care disparities. ( 1, B-R )
2. Hospitals treating patients with acute stroke should participate in stroke data registries to increase the adherence to quality indicators and guideline recommendations and improve patient outcomes. ( 1, B-NR )
3. Hospitals treating patients with acute stroke should measure and document baseline stroke severity (eg, NIHSS score) in all acute stroke patients so that risk adjustment models used to compare hospital performance can be sufficiently accurate and reliable. ( 1, B-NR )
Emergency Evaluation and Treatment
3.1. Stroke Scales
1. In patients with suspected AIS, the use of a stroke severity rating scale, preferably the NIHSS, is recommended for measuring clinical deficits at baseline and after reperfusion therapies. ( 1, B-NR )
3.2. Initial, Vascular, and Multimodal Imaging Approaches
IVT Evaluation
1. In patients with suspected AIS, emergent brain imaging with NCCT or MRI is recommended on initial evaluation to assess ischemic burden (eg, ASPECTS) and exclude intracranial hemorrhage before initiating reperfusion interventions (see Figure 2). ( 1, A )
2. In hospital systems that care for patients with suspected AIS, protocols based on process improvement initiatives should be established so that emergent brain imaging can be performed as rapidly as possible (eg, within 25 minutes) to facilitate timely reperfusion interventions. ( 1, B-NR )
3. In patients with suspected AIS and LVO, emergent vascular imaging with contrast-enhanced CTA and/or CTP should not be delayed to obtain serum creatinine concentration. ( 1, B-NR )
4. (New and of High Impact) In pediatric patients with suspected AIS, emergent brain and vascular imaging with MRI/MRA of the cervical and intracranial vessels is reasonable to identify patients with large vessel occlusion and to differentiate arterial ischemic stroke from hemorrhagic stroke or stroke mimics. ( 2a, C-LD )
5. (New and of High Impact) In pediatric patients with suspected AIS, emergent brain and vascular imaging with CT/CTA of the cervical and intracranial vessels is reasonable if MRI/MRA imaging is not available immediately (within 25 minutes) to identify patients with large vessel occlusion. ( 2a, C-LD )
6. In patients with suspected AIS who awaken from symptoms or have unknown time of onset >4.5 hours from last known well, but are otherwise eligible for thrombolysis, MRI DWI-FLAIR mismatch selection can be useful to determine eligibility for extended window IVT. ( 2a, B-R )
7. In patients with suspected AIS who awaken with symptoms or have unknown time of onset 4.5 to 24 hours from last known well, CTP or MR DWI-PWI (perfusion-weighted imaging) selection with automated postprocessing software analysis can be useful to determine eligibility for extended window IVT. ( 2a, B-R )
Endovascular Thrombectomy Evaluation
8. In patients with suspected AIS and LVO presenting within 24 hours of last known well, emergent brain and vascular imaging (CT/CTA or MRI/MRA) of the cervical and intracranial vessels should be performed as rapidly as possible for EVT selection and treatment planning. ( 1, A )
9. In patients with suspected AIS and LVO presenting within 6 to 24 hours of last known well, adjunctive CTP, MRI (DWI-FLAIR mismatch), or MR DWI-PWI with automated postprocessing software analysis can be useful in the evaluation for EVT, if immediately available. ( 2a, A )
10. In patients with suspected AIS and LVO based on prehospital assessment with a validated stroke severity scale (eg, RACE >4) and eligible for EVT, direct triage to the angiography suite (DTAS) for flat-panel head CT versus conventional imaging workflow followed by catheter-based angiography may be considered to reduce time to intervention and improve functional outcomes. ( 2b, B-R )
11. In emergently transferred patients with suspected AIS due to LVO (based on imaging or clinical assessment) and eligible for EVT, DTAS may be considered without repeat brain imaging (unless there is clinical change or transfer delay) on arrival to the thrombectomy center. ( 2b, B-NR )
Figure 2. ASPECTS: Alberta Stroke Program Early CT Score
CT indicates computed tomography; and MCA, middle cerebral artery.
Table 1. Imaging Criteria Used in the Extended Window Thrombolysis Trials
| Trial name | Imaging criteria |
|---|---|
| WAKE-UP | DWI/FLAIR mismatch: presence of an abnormal signal on DWI and no visible signal change on FLAIR in the region of the acute stroke |
| THAWS | DWI/FLAIR mismatch: presence of an abnormal signal on DWI and no marked signal change on FLAIR in the region of the acute stroke |
| EPITHET | PWI/DWI mismatch: PWI/DWI volume ratio >1.2 and PWI–DWI volume ≥10 mL (PWI volume defined as Tmax >2 s) |
| ECASS-4 | PWI/DWI mismatch: PWI/DWI volume ratio of ≥1.2 and PWI ≥20 mL |
| EXTEND | CTP or DWI/PWI mismatch: ischemic penumbra to core volume ratio >1.2, penumbra – core volume >10 mL, and core volume <70 mL (core defined as <30% of normal regions on CTP or DWI volume; penumbra defined as Tmax >6 s on CTP or PWI) |
| TIMELESS | CTP or DWI/PWI mismatch: ischemic penumbra to core volume ratio >1.8, penumbra volume >15 mL, and core volume <70 mL (core defined as <30% of normal regions on CTP or DWI volume; penumbra defined as Tmax >6 s on CTP or PWI using RAPID automated postprocessing) |
| TRACE-3 | CTP or DWI/PWI mismatch: ischemic penumbra to core volume ratio >1.8, penumbra volume >15 mL, and core volume <70 mL (core defined as <30% of normal regions on CTP or DWI volume; penumbra defined as Tmax >6 s on CTP or PWI using iStroke software) |
CTP indicates computed tomographic perfusion; DWI, diffusion-weighted imaging; FLAIR, fluid-attenuated inversion recovery; and PWI, perfusion-weighted imaging.
3.3. Other Diagnostic Tests
1. In patients with suspected acute stroke, baseline electrocardiographic assessment is recommended but should not delay initiation of IVT or EVT. ( 1, C-LD )
2. In patients with suspected acute stroke, baseline troponin is recommended but should not delay initiation of IVT or EVT. ( 1, B-NR )
General Supportive Early Management
4.1. Airway, Breathing, and Oxygenation
1. In patients with acute stroke and decreased consciousness or bulbar dysfunction, airway support and ventilatory assistance are recommended as needed to provide airway maintenance, protection and adequate ventilation and oxygenation. ( 1, C-LD )
2. In patients with AIS with hypoxia, supplemental oxygen should be provided to maintain oxygen saturation (SpO2) >94%. ( 1, C-LD )
4. In patients with AIS due to arterial air embolism, hyperbaric oxygen (HBO) may be reasonable to improve clinical outcome. ( 2b, B-NR )
5. In patients with AIS without hypoxia who are ineligible for EVT, supplemental oxygen is not recommended to improve functional outcomes. ( 3 - No Benefit, B-R )
6. In patients with AIS, not associated with air embolism, HBO is not recommended to improve functional outcomes. ( 3 - No Benefit, B-R )
4.2. Head Positioning
1. In patients with AIS overall, there is no benefit of routine 0-degree head positioning compared with 30 degrees for 24 hours, to improve functional outcome. ( 3 - No Benefit, B-R )
2. In patients with AIS with probable large artery atherosclerosis cause for whom no reperfusion intervention is available, there is no benefit of routine Trendelenburg positioning (−20 degrees) compared with 0- to-30- degree head positioning to improve functional outcome. ( 3 - No Benefit, B-R )
4.3. Blood Pressure Management
General Recommendations (Including Without Reperfusion Therapy)
1. In patients with AIS, hypotension and hypovolemia should be corrected to maintain systemic perfusion levels necessary to support organ function. ( 1, C-LD )
2. In patients with AIS, early treatment of hypertension is indicated when required by comorbid conditions (eg, concomitant acute coronary event, acute heart failure, aortic dissection, postthrombolysis sICH, or preeclampsia/ eclampsia) to reduce the risk of complications. ( 1, C-EO )
3. In patients with BP ≥220/120 mm Hg who did not receive IVT or EVT and have no comorbid conditions requiring urgent antihypertensive treatment, the benefit of initiating or reinitiating treatment of hypertension within the first 48 to 72 hours is uncertain. ( 2b, C-EO )
4. In patients with BP <220/120 mm Hg who did not receive IVT or EVT and do not have a comorbid condition requiring urgent antihypertensive treatment, initiating or reinitiating treatment of hypertension within the first 48 to 72 hours after an AIS is not effective to prevent death or dependency. ( 3 - No Benefit, A )
Before Reperfusion Treatment
5. Patients with AIS who have elevated BP and are otherwise eligible for treatment with IVT should have their SBP lowered to <185 mm Hg and diastolic blood pressure (DBP) <110 mm Hg before IVT therapy is initiated to reduce hemorrhagic complications. ( 1, B-NR )
6. In patients for whom EVT is planned and who have not received IVT therapy, it is reasonable to maintain BP ≤185/110 mm Hg before the procedure to avoid complications and improve patient outcomes. ( 2a, B-NR )
After IVT
7. BP should be maintained at <180/105 mm Hg for at least the first 24 hours after IVT treatment. ( 1, B-R )
8. (New and of High Impact) In patients with mild to moderate severity AIS who have been treated with IVT, intensive SBP reduction (target of <140 mm Hg compared with <180 mm Hg) is not recommended because it is not associated with an improvement in functional outcome. ( 3 - No Benefit, B-R )
After Endovascular Thrombectomy
9. In patients who undergo EVT, it is reasonable to maintain BP at a level ≤180/105 mm Hg during and for 24 hours after the procedure. ( 2a, B-NR )
10. (New and of High Impact) In patients with AIS with LVO of the anterior circulation who have been successfully recanalized by endovascular therapy (mTICI 2b, 2c, or 3) and without other indication for blood pressure management target, intensive SBP reduction target of <140 mm Hg for the first 72 hours is harmful and not recommended. ( 3 - Harm, A )
4.4. Temperature Management
1. In patients with AIS who have hyperthermia, targeting normothermia, including using nurse-initiated protocols for managing fever, is recommended for improving functional outcomes and reducing death. ( 1, B-R )
2. In patients with AIS and hyperthermia, sources of hyperthermia, such as infection, should be identified and treated to avoid complications. ( 1, C-EO )
3. In patients with AIS and normothermia, treatment with induced hypothermia or prophylactic fever prevention is not recommended for the purpose of improving outcomes. ( 3 - No Benefit, B-R )
4.5. Blood Glucose Management
1. In patients with AIS, hypoglycemia (blood glucose <60 mg/dL) should be treated to avoid complications. ( 1, C-LD )
2. In patients with AIS, it is reasonable to treat persistent hyperglycemia to achieve blood glucose levels in a range of 140 to 180 mg/dL with close monitoring to prevent worse functional outcomes. ( 2a, C-LD )
3. (New and of High Impact) In hospitalized patients with AIS with hyperglycemia, treatment with IV insulin to achieve blood glucose levels in the range of 80 to 130 mg/dL is not recommended to improve 3-month functional outcomes. ( 3 - No Benefit, A )
4.6. IV Thrombolytics
4.6.1. Thrombolysis Decision-Making
General Principles
1. In adult patients with AIS with disabling deficits, regardless of NIHSS score), and eligible for IVT, faster treatment improves functional outcomes. ( 1, A )
2. (New and of High Impact) In adult patients with AIS who are eligible for IVT within 4.5 hours of symptom onset, treatment should be initiated as quickly as possible, assuring safe administration and avoiding potential delays associated with additional multimodal neuroimaging, such as CTA/ MRA, and CT/MR perfusion imaging. ( 1, B-NR )
3. In patients with AIS undergoing IVT, health care professionals should be prepared to treat potential emergent adverse effects, including bleeding complications and angioedema, which may cause partial airway obstruction, to reduce poor clinical outcomes. ( 1, B-NR )
4. In patients with AIS eligible for IVT, health care professionals should discuss its potential risks and benefits with competent patients and/or available patient representatives, when feasible, to ensure shared decision-making. ( 1, C-EO )
5. In patients with suspected ischemic stroke, treating health care professionals should determine blood glucose levels before IVT initiation to assess and urgently treat severe hypoglycemia and hyperglycemia, which may mimic acute stroke presentations. ( 1, B-NR )
6. In patients with suspected ischemic stroke with severe hypoglycemia or hyperglycemia, if symptoms of disabling stroke persist despite correction to normoglycemia, administration of IVT is recommended to improve functional outcomes. ( 1, C-LD )
7. In patients with AIS who are otherwise eligible for IVT with early ischemic change of mild to moderate extent (other than frank hypodensity attributable to the clinical presentation) on initial brain imaging, IVT is recommended to improve functional outcome. ( 1, A )
8. In eligible adult patients with AIS presenting with mild non-disabling stroke deficits (eg, isolated sensory syndrome in many cases) within 4.5 hours of symptom onset or last known well, IVT is not recommended as it has not shown superiority in improving functional outcomes compared to double antiplatelet treatment. ( 3 - No Benefit, B-R )
Bleeding Risk
9. In suspected patients with AIS who are taking single or DAPT and are otherwise eligible for IVT, IVT is recommended to improve functional outcomes despite an increase in risk of sICH compared with no antiplatelet therapy. ( 1, B-NR )
10. In patients with AIS within 4.5 hours of last known well and eligible for IVT, it is reasonable that IVT not be delayed while waiting for hematologic or coagulation testing if there is no reason to suspect an abnormal result. ( 2a, B-NR )
11. In patients with AIS who are eligible for IVT within 4.5 hours of symptom onset with unknown burden of cerebral microbleeds (CMB), it is recommended that IVT be administered without first obtaining MRI to exclude CMBs. ( 1, B-NR )
12. In patients with AIS within 4.5 hours of last known well and who are eligible for IVT, administration of IVT is reasonable to achieve better functional outcomes if a small number (e.g, 1–10) of CMBs was demonstrated on MRI. ( 2a, B-NR )
13. In patients with AIS within 4.5 hours of last known well and who are eligible for IVT, if they previously had a high burden (eg, >10) of CMBs demonstrated on MRI, usefulness of IVT is uncertain as it may be associated with an increased risk of sICH. ( 2b, B-NR )
Pediatric Patients
14. In pediatric patients aged 28 days to 18 years with confirmed AIS presenting within 4.5 hours of symptom onset and disabling deficits, IVT with alteplase may be considered as it is safe, but efficacy is uncertain. ( 2b, C-LD )
Table 2. Guidance for Determining Deficits to be Clearly Disabling at Presentation
Among patients with NIHSS scores 0–5 at presentation, if the observed deficits persist, would they still be able to do basic activities of daily living and/or return to work (if applicable)?
As a guideline, while always considering individual circumstances:
The following deficits would typically be considered clearly disabling:
The following deficits may not be clearly disabling in an individual patient:
- Basic activities of daily living include bathing/dressing, ambulating, toileting, hygiene, and eating (BATHE mnemonic).
- To fully evaluate the level of deficits, the ability to ambulate and swallow independently should be assessed.
- The clinician should make this determination in consultation with the patient and available family.
As a guideline, while always considering individual circumstances:
The following deficits would typically be considered clearly disabling:
- Complete hemianopsia (≥2 on the NIHSS “vision” question)
- Severe aphasia (≥2 on the NIHSS “best language” question)
- Severe hemi-attention or extinction to >1 modality (≥2 on the NIHSS “extinction and inattention” question)
- Any weakness limiting sustained effort against gravity (≥2 on the NIHSS “motor” questions)
The following deficits may not be clearly disabling in an individual patient:
- Isolated mild aphasia (but still able to communicate meaningfully)
- Isolated facial droop • Mild cortical hand weakness (especially nondominant, NIHSS score, 0)
- Mild hemimotor loss
- Hemisensory loss
- Mild hemi sensorimotor loss
- Mild hemiataxia (but can still ambulate)
NIHSS indicates National Institutes of Health Stroke Scale.
Table 3. Management of Symptomatic Intracranial Bleeding Occurring Within 24 Hours After Administration of IV Alteplase or Tenecteplase for Treatment of AIS in Adults
- Stop alteplase infusion or tenecteplase (if still being pushed).
- Emergent CBC, PT (INR), aPTT, fibrinogen level, and type and cross-match.
- Cryoprecipitate (includes factor VIII): 10 U infused over 10–30 min to maintain fibrinogen level of ≥150 mg/dL; as a rule of thumb 10 U of cryoprecipitate increase fibrinogen level by nearly 50 mg/dL).
- Tranexamic acid 1000 mg IV infused over 10 min OR e-aminocaproic acid 4–5 g over 1 h, followed by 1 g IV until bleeding is controlled (peak onset in 3 h).
Potential for benefit in all patients, but particularly when blood products are contraindicated by patient/family or if cryoprecipitate is not available in a timely manner. - Hematology and neurosurgery consultations as necessary.
- Supportive therapy, including BP management, ICP, CPP, MAP, temperature, and glucose control.
Adapted with permission from Sloan et al, Mahaffey et al, Goldstein et al, French et al, Yaghi et al, Stone et al, and Frontera et al.
AIS indicates acute ischemic stroke; aPTT, activated partial thromboplastin time; BP, blood pressure; CBC, complete blood count; COR, class of recommendation; CPP, cerebral perfusion pressure; CT, computed tomography; ICP, intracranial pressure; INR, international normalized ratio; IV, intravenous; LOE, level of evidence; MAP, mean arterial pressure; and PT, prothrombin time.
AIS indicates acute ischemic stroke; aPTT, activated partial thromboplastin time; BP, blood pressure; CBC, complete blood count; COR, class of recommendation; CPP, cerebral perfusion pressure; CT, computed tomography; ICP, intracranial pressure; INR, international normalized ratio; IV, intravenous; LOE, level of evidence; MAP, mean arterial pressure; and PT, prothrombin time.
Table 4. Management of Orolingual Angioedema Associated With IV Thrombolytic Administration for AIS in Adults
Maintain airway
- Endotracheal intubation may not be necessary if edema is limited to the anterior tongue and lips.
- Edema involving the larynx, palate, floor of mouth, or oropharynx with rapid progression (within 30 min) poses a higher risk of requiring intubation.
- Awake fiberoptic intubation is optimal. Nasal-tracheal intubation may be required but poses risk of epistaxis after IV thrombolytic use. Cricothyroidotomy is rarely needed and also problematic after IV thrombolytic use.
- Discontinue IV thrombolytic infusion (if alteplase) and hold ACE inhibitors.
- Administer IV methylprednisolone 125 mg.
- Administer IV diphenhydramine 50 mg.
- Administer ranitidine 50 mg IV or famotidine 20 mg IV.
- If there is further increase in angioedema, administer 0.1% epinephrine (1 mg/mL concentration) 0.3 mL intramuscularly or by nebulizer 0.5 mg/dL.
- Icatibant, a selective bradykinin B2 receptor antagonist, 3 mL (30 mg) subcutaneously in abdominal area; additional injection of 30 mg may be administered at intervals of 6 h not to exceed a total of 3 injections in 24 h; and plasma-derived C1 esterase inhibitor (20 IU/kg) has been successfully used in hereditary angioedema and ACE inhibitor-related angioedema.
- Provide supportive care.
Adapted with permission from Sloan et al, Mahaffey et al, Goldstein et al, French et al, Yaghi et al, Stone et al, and Frontera et al.
ACE indicates angiotensin-converting enzyme; AIS, acute ischemic stroke; COR, class of recommendation; IV, intravenous; and LOE, level of evidence.
ACE indicates angiotensin-converting enzyme; AIS, acute ischemic stroke; COR, class of recommendation; IV, intravenous; and LOE, level of evidence.
4.6.2. Choice of Thrombolytic Agent
1. (New and of High Impact) In adult patients with AIS presenting within 4.5 hours of symptom onset or last known well and eligible for IVT, tenecteplase at a dose of 0.25 mg/kg body weight (max 25 mg) or alteplase at a dose of 0.9 mg/kg body weight (max 90 mg) is recommended to improve functional outcomes. ( 1, A )
2. In adult patients with AIS presenting within 4.5 hours of symptom onset or last known well and eligible for IVT, tenecteplase at a dose of 0.4 mg/kg body weight is not recommended. ( 3 - No Benefit, A )
Table 5. Treatment of AIS in Adults*: IVT
- Alteplase: Infuse 0.9 mg/kg (maximum dose 90 mg) over 60 min, with 10% of the dose given as a bolus over 1 min.
- Tenecteplase: Push 0.25 mg/kg (up to maximum 25 mg) based on patient body weight†:
Patient weight (kg) TNK (mg) Volume TNK to be administered (mL) <60 kg 15 3 60 kg to <70 kg 17.5 3.5 70 kg to <80 kg 20 4 80 kg to <90 kg 22.5 4.5 ≥90 kg 25 5 - Admit the patient to an intensive care or stroke unit for monitoring.
- If the patient develops severe headache, acute hypertension, nausea, or vomiting or has a worsening neurological examination, discontinue the infusion (if IV alteplase is being administered) and obtain an emergency head CT scan.
- Measure BP and perform neurological assessments every 15 min during and after IVT administration for 2 h, then every 30 min for 6 h, then hourly until 24 h after IV alteplase treatment.
- Increase the frequency of BP measurements if SBP is >105 mm Hg; administer antihypertensive medications to maintain BP at or below these levels.
- Delay placement of nasogastric tubes, indwelling bladder catheters, or intraarterial pressure catheters if the patient can be safely managed without them.
- Obtain a follow-up CT or MRI scan at 24 h after IVT before starting anticoagulants or antiplatelet agents.
* Dosing for pediatric patients has not been determined.
† If <50kg and accurate weight is known, dosing per 1-kg band may be used. Do not delay thrombolysis to obtain exact weight — timely treatment is critical. With estimated weights, dosing per 1-kg band is not necessarily safer than 10-kg band dosing.
AIS indicates acute ischemic stroke; BP, blood pressure; CT, computed tomography; DBP, diastolic blood pressure; IV, intravenous; IVT, intravenous thrombolysis; MRI, magnetic resonance imaging; and SBP, systolic blood pressure.
† If <50kg and accurate weight is known, dosing per 1-kg band may be used. Do not delay thrombolysis to obtain exact weight — timely treatment is critical. With estimated weights, dosing per 1-kg band is not necessarily safer than 10-kg band dosing.
AIS indicates acute ischemic stroke; BP, blood pressure; CT, computed tomography; DBP, diastolic blood pressure; IV, intravenous; IVT, intravenous thrombolysis; MRI, magnetic resonance imaging; and SBP, systolic blood pressure.
4.6.3. Extended Time Windows for Intravenous Thrombolysis
1. In patients with AIS who (a) have unknown time of onset and are within 4.5 hours from symptom recognition and (b) have an MRI-DWI lesion smaller than one-third of the MCA territory and no marked signal change on FLAIR, IVT administered within 4.5 hours of stroke symptom recognition can be beneficial to improve functional outcomes. ( 2a, B-R )
2. (New and of High Impact) In patients with AIS who are not eligible for endovascular thrombectomy but have salvageable ischemic penumbra detected on automated perfusion imaging and who (a) awake with stroke symptoms within 9 hours from the midpoint of sleep or (b) are 4.5–9 hours from last known well, IV thrombolysis can be beneficial to improve functional outcomes. ( 2a, B-R )
3. In patients with AIS due to LVO with salvageable ischemic penumbra, presenting within 4.5 to 24 hours from symptom onset or last known well, and who cannot receive EVT, treatment with IVT directed by individuals with expertise in thrombolytic stroke care may be beneficial to improve functional outcomes. ( 2b, B-R )
4.6.4. Other IV Fibrinolytics and Sonothrombolysis
Other IV Fibrinolytics
1. In eligible patients with AIS presenting within 4.5 hours from last known normal and not undergoing EVT, IV reteplase, instead of alteplase, may be considered to increase the odds of excellent functional outcome at 90 days. ( 2b, B-R )
2. In eligible patients with AIS within 4.5 hours from last known normal and not undergoing EVT, IV mutant prourokinase, instead of alteplase, may be considered due to lower odds of bleeding and noninferiority for odds of excellent functional outcome at 90 days. ( 2b, B-R )
3. In eligible patients with AIS presenting within 3 to 9 hours from last known normal, IV desmoteplase is not recommended for improving functional independence at 90 days. ( 3 - No Benefit, A )
4. In eligible patients with AIS within 4.5 hours from last known normal, IV mutant prourokinase in conjunction with low-dose alteplase is not recommended to improve functional outcomes. ( 3 - No Benefit, B-R )
5. In eligible patients with AIS within 6 hours from last known normal, IV urokinase is not beneficial for decreasing the odds of death or dependency. ( 3 - No Benefit, B-R )
6. In eligible patients with AIS within 6 hours from last known normal, IV streptokinase should not be administered because it does not result in improved rate of functional independence at 90 days and is associated with increased early mortality. ( 3 - Harm, A )
Sonothrombolytics
7. In patients with AIS, sonothrombolysis as an adjunctive therapy to IVT compared with IVT alone is not recommended as it did not increase the odds of early neurological improvement nor improve functional outcome at 90 days. ( 3 - No Benefit, A )
4.6.5. Other Specific Circumstances
1. In eligible adult patients with AIS with known sickle cell disease, IVT can be beneficial to improve functional outcome without increased sICH, life-threatening systemic hemorrhage, or other thrombolytic complications. ( 2a, B-NR )
2. In adults with acute nonarteritic central retinal artery occlusion (CRAO) causing disabling visual loss, and who are otherwise eligible for IVT, the usefulness of treatment with IVT within 4.5 hours of time last known well is uncertain. ( 2b, C-LD )
Table 6. Other Situations That May Arise in Thrombolysis Decision-Making
Conditions in which benefits of intravenous thrombolysis generally are greater than risks of bleeding
Scenarios with relatively low concerns but not linked to actionable recommendations.
Extracranial cervical dissections
IV thrombolysis in AIS known or suspected to be associated with extracranial cervical arterial dissection is reasonably safe within 4.5 h and probably recommended.
Extra-axial intracranial neoplasms
The risk of harm of IV thrombolysis in patients with AIS and extra axial intracranial neoplam is likely low. Benefit likely outweighs risk in this population and IV thrombolysis should be considered.
Angiographic procedural stroke
IV thrombolysis in patients with AIS during or immediately post angiography should be considered as benefit likely outweighs risk in this population.
Unruptured intracranial aneurysm
The risk of harm of IV thrombolysis in patients with AIS and unruptured intracranial aneurysm is likely low. Benefit likely outweighs risk in this population and treatment with IV thrombolysis should be considered.
History of GI/GU bleeding
IV thrombolysis in AIS patients with previous remote history of GI or GU bleeding that is stable may be candidates for IV thrombolysis. Consideration of benefit and risk on an individual basis in conjunction with GI or GU consultation is appropriate.
History of MI
IV thrombolysis in AIS patients with remote history of MI probably has greater benefit than risk.
Recreational drug use
IV thrombolysis in AIS patients with known recreational drug use probably has greater benefit than risk in most patients and should be considered.
Uncertainty of stroke diagnosis/stroke mimics
When uncertain if a patient is presenting with symptoms due to stroke vs a stroke mimic, unless there are absolute contraindications, the risk of harm with IV thrombolysis is low. The benefit of IV thrombolysis likely outweighs risk in these patients.
Moya-Moya
IV thrombolysis in AIS patients with Moya-Moya disease does not appear to have an increased risk of ICH and likely provides benefit that outweighs risk.
Conditions that are relative contraindications
Moderate caution where additional consideration may be warranted.
Pre-existing disability
The benefits vs risks of offering IV thrombolysis in patients with pre-existing disability and/or frailty remain uncertain. Treatment should be determined on an individual basis.
DOAC exposure
In patients with disabling symptoms and recent DOAC exposure (<48 hours) who are within the window for alteplase/tenecteplase, the safety of IV thrombolysis is unknown. Emerging but limited observational data suggest IV thrombolysis may be considered after a thorough benefit vs risk analysis on an individual basis. Benefit vs risk assessments should include considering the timing of the latest DOAC administration, renal function, stroke severity, and availability of endovascular thrombectomy as well as availability of DOAC reversal agents and DOAC-specific anti-factor Xa/ thrombin time assays acknowledging the potential for delay in thrombolysis and potential increased thrombotic risk. All aspects of DOAC management (timing, reversal agent use, assay results), should be recorded carefully to facilitate ongoing safety analyses. Definitive clinical trials are needed to establish the safety of IV thrombolysis in DOAC patients.
Ischemic stroke w/ in 3 months
Use of IV thrombolysis in patients presenting with AIS who have had a prior ischemic stroke within 3 months may be at increased risk of intracranial hemorrhage. Potential increased risk as a result of the timing and size of the stroke should be weighed against the benefits of offering IV thrombolysis in an individualized manner in such patients.
Prior ICH
IV thrombolysis administration in patients who have a history of ICH may increase the risk of symptomatic hemorrhage. Patients with known amyloid angiopathy may be considered as having higher risk than patients with ICH due to modifiable conditions (eg, HTN, coagulopathy). IV thrombolysis may have greater treatment benefit than risk in these latter patients. Treatment should be determined on an individual basis.
Recent major non-CNS trauma (w/in 14 days and 3 months)
Patients with recent major trauma w/in 14 days and 3 months of their AIS may be at increased risk of harm and serious systemic hemorrhage requiring transfusion from IV thrombolysis. Individual consideration of risk vs benefit, involved areas, and consultation with surgical experts are appropriate.
Recent major non-CNS surgery w/in 10 days
Patients with recent major surgery within 10 days of AIS may be at increased risk of harm from IV thrombolysis. Individual consideration of risk vs benefit, surgical area, and consultation with surgical experts are appropriate.
Recent GI/GU bleeding w/in 21 days
Patients with recent GI or GU bleeding within 21 days of their AIS may be at increased risk of harm from IV thrombolysis. Individual consideration of risk vs benefit and consultation with GI or GU experts to determine if the GI/GU bleeding has been treated and risk modified/reduced is recommended.
Intracranial arterial dissection
The safety of IV thrombolysis in patients with AIS due to intracranial arterial dissection is unknown.
Intracranial vascular malformations
The safety of IV thrombolysis for patients presenting with AIS who are known to harbor an unruptured and untreated intracranial vascular malformation is unknown.
Recent STEMI w/ in 3 months
Patients with recent STEMI may be at risk for increased harm from IVT. For patients with history of STEMI within 3 months, individual consideration of risk and benefit should be determined in conjunction with an emergent cardiology consultation. For patients with very recent STEMI (previous several days), the risk of hemopericardium should be considered relative to potential benefit. For patients presenting with concurrent AIS and acute STEMI, treatment with IV thrombolysis should be at a dose appropriate for cerebral ischemia and in conjunction with emergent cardiology consultation. Consideration of timing, type and severity of STEMI to determine the risk vs benefit is warranted.
Acute pericarditis
IV thrombolysis for patients with major AIS likely to produce severe disability and acute pericarditis, may be reasonable in individual cases. Emergent cardiologic consultation is warranted.
Left atrial or ventricular thrombus
IV thrombolysis for patients with known left atrial or ventricular thrombus presenting with major AIS likely to produce severe disability may be reasonable in individual cases. Emergent cardiologic consultation is warranted.
Systemic active malignancy
The safety of IV thrombolysis in patients with systemic active malignancy is unknown. Emergent consultation with oncology to assess risk/benefit is warranted. Consideration of type, stage, and active complications of cancer to determine the risk vs benefit is warranted.
Pregnancy and post-partum period
IV thrombolysis may be considered in pregnancy and post-partum period when the benefits of treating moderate or severe stroke outweighs the anticipated risk of uterine bleeding. Emergent obstetrical consultation is warranted.
Dural puncture w/ in 7 days
IV thrombolysis for patients with AIS post-dural puncture may be considered in individual cases, even in instances when they may have undergone a lumbar dural puncture in the preceding 7 days.
Arterial puncture w/ in 7 days
The safety of IV thrombolysis in patients with AIS who have had an arterial puncture of a noncompressible blood vessel (eg, subclavian artery line) in the 7 days preceding the stroke symptoms is unknown.
Moderate to severe traumatic brain injury ≥14 days to 3 months
IV thrombolysis may be considered in AIS patients with recent moderate to severe traumatic brain injury (between 14 days and 3 months). Careful consideration should be made based on the type and severity of traumatic injury and in consultation with neurosurgical and neurocritical care team members.
Neurosurgery ≥14 days to 3 months
For patients with AIS and a history of intracranial/spinal surgery between 14 days and 3 months, IV thrombolysis may be considered on an individual basis. Consultation with neurosurgical team members is recommended.
Conditions that are considered absolute contraindications
Higher relative harm requiring careful examination but remains unsupported by clinical evidence.
CT with extensive hypodensity
IV thrombolysis should not be administered to patients whose brain imaging exhibits extensive regions of clear hypodensity that appear to be responsible for the clinical symptoms of stroke. Clear hypodensity is when the degree of hypodensity is greater than the density of contralateral unaffected white matter.
CT with hemorrhage
IV thrombolysis should not be administered to patients whose CT brain imaging reveals an acute intracranial hemorrhage.
Moderate to severe traumatic brain injury <14 days
IV thrombolysis is likely contraindicated in AIS patients with recent moderate to severe traumatic brain injury (within 14 days) that incurred >30 minutes of unconsciousness and Glasgow Coma Scale of <13 OR evidence of hemorrhage, contusion, or skull fracture on neuroimaging.
Neurosurgery <14 days
For patients with AIS and a history of intracranial/spinal surgery within 14 days, IV thrombolysis is potentially harmful and should not be administered.
Acute spinal cord injury within 3 months
IV thrombolysis is likely contraindicated in AIS patients with spinal cord injury within 3 months.
Intra-axial neoplasm
For patients with AIS who harbor an intra-axial intracranial neoplasm, treatment with IV thrombolysis is potentially harmful and should not be administered.
Infective endocarditis
For patients with AIS and symptoms consistent with infective endocarditis, treatment with IV thrombolysis should not be administered.
Severe coagulopathy or thrombocytopenia
The safety and efficacy of IV thrombolysis for AIS in patients with platelets <100,000/mm3, INR>1.7, aPTT>40s, or PT>15s is unknown though may substantially increase risk of harm and should not be administered.
In patients without recent use of warfarin or heparin, treatment with IV thrombolysis can be initiated before availability of coagulation test results but should be discontinued if INR>1.7, PT, or PTT is abnormal by local laboratory standards.
In patients without recent use of warfarin or heparin, treatment with IV thrombolysis can be initiated before availability of coagulation test results but should be discontinued if INR>1.7, PT, or PTT is abnormal by local laboratory standards.
Aortic arch dissection
For patients with AIS and known or suspected aortic arch dissection, treatment with IV thrombolysis is potentially harmful and should not be administered.
Amyloid related imaging abnormalities (ARIA)
The risk of thrombolysis related ICH in patients on amyloid immunotherapy or with ARIA is unknown and IV thrombolysis should be avoided in such patients.
AIS indicates acute ischemic stroke; aPTT, activated partial thromboplastin time; CNS, central nervous system; CT, computed tomography; DOAC, direct oral anticoagulant; GI, gastrointestinal; GU, genitourinary; HTN, hypertension; ICH, intracerebral hemorrhage; INR, international normalized ratio; IRB, institutional review board; IV, intravenous; MI, myocardial infarction; PT, prothrombin time; and PTT, partial thromboplastin time.
4.7. Endovascular Thrombectomy
4.7.1. Concomitant With IVT
1. In patients with AIS who are eligible for both IVT and EVT, IVT is safe and recommended to improve overall reperfusion efficacy and clinical outcomes. ( 1, A )
2. In patients with AIS who are eligible for both IVT and EVT, IVT should be administered as rapidly as possible, without observation, to assess clinical response or delay in initiating EVT, to improve treatment times and clinical outcomes. ( 1, A )
4.7.2. Endovascular Thrombectomy for Adult Patients
Thrombectomy 0 to 6 Hours After Onset of Symptoms, ASPECTS 3 to 10
1. (New and of High Impact) In patients with AIS from anterior circulation proximal LVO of the ICA or M1, presenting within 6 hours from onset of symptoms, with NIHSS score ≥6, prestroke mRS score of 0 to 1, and ASPECTS 3 to 10, EVT is recommended to improve functional clinical outcomes and reduce mortality. ( 1, A )
Thrombectomy 6 to 24 Hours After Onset of Symptoms, ASPECTS 6 to 10
Thrombectomy 6 to 24 Hours After Onset of Symptoms, ASPECTS 3 to 5
3. (New and of High Impact) In selected patients* with AIS from anterior circulation proximal LVO of the ICA or M1, presenting between 6 and 24 hours from onset of symptoms, with age <80 years, NIHSS score ≥6, prestroke mRS score 0 to 1, ASPECTS 3 to 5, and without significant mass effect on imaging, EVT is recommended to improve functional clinical outcomes and reduce mortality. ( 1, A )
* Limited generalizability in specific subpopulations: Specific patient groups were underrepresented or excluded in the trials supporting this recommendation. Consequently, the applicability of these findings is limited in individuals >80 years, those with renal failure, patients with refractory hypertension (SBP ≥185 mm Hg or DBP ≥110 mm Hg), comorbid psychiatric or medical illnesses that confound neurological assessments, or patients with a life expectancy <3 months.
Thrombectomy 0 to 6 Hours After Onset of Symptoms, ASPECTS 0 to 2
4. (New and of High Impact) In selected patients† with AIS from anterior circulation proximal LVO of the ICA or M1 presenting within 6 hours from onset of symptoms, with age <80 years, NIHSS score ≥6, prestroke mRS 0 to 1, ASPECTS 0 to 2, and without significant mass effect on imaging, EVT is reasonable to improve functional clinical outcomes and reduce mortality. ( 2a, B-R )
† Limited generalizability in specific subpopulations: Specific patient groups were underrepresented or excluded in the trials supporting this recommendation. Consequently, the applicability of these findings is limited in individuals >80 years, those with significant head and neck vessel tortuosity, comorbid psychiatric or medical conditions that confound neurological assessments, seizures at stroke onset that hinder accurate NIHSS evaluations, a strong suspicion of underlying intracranial stenosis, or a life expectancy <6 months.
Thrombectomy 0 to 6 Hours After Onset of Symptoms With Mild Preexisting Disability
5. (New and of High Impact) In patients with AIS from anterior circulation proximal LVO of the ICA or M1 presenting within 6 hours from onset of symptoms, with NIHSS score ≥6, and ASPECTS ≥6, who have a prestroke mRS score of 2, EVT is reasonable to improve functional clinical outcomes and reduce accumulated disability. ( 2a, B-NR )
Thrombectomy 0 to 6 Hours After Onset of Symptoms With Moderate Preexisting Disability
6. In patients with AIS from anterior circulation proximal LVO of the ICA or M1 presenting within 6 hours from onset of symptoms, with NIHSS score ≥6, and ASPECTS of ≥6, who have a prestroke mRS score of 3 to 4, EVT might be reasonable to improve functional clinical outcomes and reduce accumulated disability. ( 2b, B-NR )
Thrombectomy 0 to 6 Hours for Dominant Proximal M2 Division MCA Occlusions
7. In patients with AIS from occlusion of the dominant proximal M2 division of the MCA presenting within 6 hours from onset of symptoms with a prestroke mRS score of 0 to 1, NIHSS score of ≥6, and ASPECTS of ≥6, EVT is reasonable to improve functional outcomes, but the benefits are uncertain. ( 2a, B-NR )
Thrombectomy 0 to 6 Hours for Nondominant Proximal M2 Division MCA, Distal MCA, Anterior Cerebral Artery, and Posterior Cerebral Artery Occlusions
8. In patients with AIS from occlusion of the proximal nondominant or codominant division proximal M2 segment of the MCA, or distal MCA, anterior cerebral artery (ACA), or posterior cerebral artery (PCA), EVT is not recommended to improve functional outcomes. ( 3 - No Benefit, A )
CT hypodensity volume as a predictor of poor outcomes: In an exploratory analysis of the SELECT2 trial, a threshold of ≥26 mL of severe CT hypodensity, defined as the lower 99% CI of the contralateral thalamic gray matter (≤26 Hounsfield units), was associated with diminished treatment benefit from EVT. Patients with CT hypodensity above this threshold derived no functional benefit and instead experienced increased risks, including cerebral edema and the need for hemicraniectomy.
4.7.3. Posterior Circulation Stroke
1. (New and of High Impact) In patients with AIS, with basilar artery occlusion, a baseline mRS score of 0 to 1, NIHSS score ≥10 at presentation, and PC-ASPECTS ≥6 (mild ischemic damage), EVT within 24 hours from onset of symptoms is recommended to achieve better functional outcome and reduce mortality. ( 1, A )
4.7.4. Endovascular Techniques
Thrombectomy General Techniques
1. In patients with AIS due to an LVO, EVT with stent retrievers, contact aspiration, or combination techniques is recommended to achieve rapid and adequate reperfusion. ( 1, A )
2. In patients with AIS undergoing EVT, reperfusion to an extended TICI grade 2b/2c/3 is recommended as early as possible within the therapeutic window to achieve maximum functional benefit at 90 days. ( 1, A )
3. In patients with AIS undergoing EVT, either general anesthesia or procedural sedation are recommended to facilitate EVT. ( 1, B-R )
4. In patients with AIS undergoing EVT, the use of a proximal balloon to guide catheters to achieve improved outcomes remains uncertain. ( 2b, B-R )
5. In patients with AIS from occlusion of medium or distal vessels of the anterior, middle (nondominant or codominant M2, M3), or posterior cerebral arteries, EVT with stent retrievers is of no benefit for improving functional outcomes. ( 3 - No Benefit, A )
Thrombectomy Adjunctive Techniques
6. In patients with AIS undergoing EVT in the setting of tandem extracranial-intracranial anterior circulation occlusions, acute treatment of both, including emergent extracranial stenting, may be reasonable to achieve higher good functional outcome. ( 2b, B-NR )
7. In patients with AIS in the setting of failed EVT, the use of rescue intracranial balloon angioplasty and/or stenting to improve functional outcome remains uncertain. ( 2b, B-NR )
8. In patients with AIS who achieve complete or near-complete EVT (modified TICI 2b or greater), the administration of adjunctive intraarterial thrombolytics with urokinase, alteplase, or tenecteplase may be reasonable to improve cerebral reperfusion and 90-day functional outcome. ( 2b, B-R )
9. (New and of High Impact) In the management of patients with AIS in the setting of LVO, preoperative administration of tirofiban before EVT is not useful to improve 90-day functional outcome. ( 3 - No Benefit, B-R )
4.7.5. Endovascular Thrombectomy in Pediatric Patients
1. In pediatric patients ≥6 years with acute neurological symptoms and ischemic stroke due to LVO and within 6 hours from symptom onset, EVT can be effective if performed by experienced neurointerventionalists to improve functional outcomes. ( 2a, B-NR )
2. In pediatric patients ≥6 years with acute neurological symptoms and ischemic stroke due to LVO, 6 to 24 hours from symptom onset, and with potentially salvageable brain tissue, EVT can be effective to improve functional outcomes. ( 2a, B-NR )
3. In pediatric patients aged 28 days to 6 years with acute neurological symptoms, including first-time seizure and AIS due to LVO, within 24 hours from symptom onset, and with potentially salvageable brain tissue, EVT performed by neurointerventionalists with pediatric experience may be reasonable to improve functional outcomes. ( 2b, B-NR )
Figure 3. Algorithm for Management of AIS Eligibility for EVT
4.8. Antiplatelet Treatment
General Principles for Early Antiplatelet Therapy
1. In patients with AIS, administration of aspirin is recommended within 48 hours after stroke onset to reduce risk of death and dependency. ( 1, A )
2. In patients with AIS who have received IVT, the risk of antiplatelet therapy in the first 24 hours after IVT (with or without mechanical thrombectomy) is uncertain. Use might be considered in the presence of concomitant conditions for which such treatment given in the absence of IVT is known to provide substantial benefit or when withholding such treatment is known to cause substantial risk. ( 2b, B-NR )
3. In patients with AIS, the efficacy of IV tirofiban to improve clinical outcomes is not well established. ( 2b, B-R )
4. In patients with AIS, the administration of IV abciximab is not recommended due to increased bleeding complications. ( 3 - Harm, B-R )
11. In patients with ischemic stroke and AF without active CAD or recent intravascular stent, the routine addition of antiplatelet therapy to oral anticoagulation is potentially harmful because of increased bleeding risk and is not recommended. ( 3 - Harm, B-NR )
Early Secondary Prevention
5. In patients with noncardioembolic AIS or TIA, antiplatelet therapy is indicated in preference to oral anticoagulation to reduce the risk of recurrent ischemic stroke and other cardiovascular events, while minimizing the risk of bleeding. ( 1, A )
6. In patients with noncardioembolic AIS or TIA, the selection of an antiplatelet agent for early secondary stroke prevention should be individualized on the basis of patient risk factor profiles, cost, tolerance, relative known efficacy of the agents, and other clinical characteristics. ( 1, C-EO )
7. In patients with AIS and extracranial carotid or vertebral arterial dissection, treatment with either antiplatelet or anticoagulant therapy for at least 3 months is reasonable to prevent recurrent stroke. ( 2a, B-R )
10. In patients with noncardioembolic ischemic stroke, treatment with triple antiplatelet therapy (aspirin and clopidogrel and dipyridamole) for secondary stroke prevention should not be administered due to increased risk of bleeding. ( 3 - Harm, B-R )
Dual Antiplatelet Therapy for Minor AIS and High-Risk TIA
12. In patients with minor (NIHSS score ≤3) noncardioembolic AIS or high-risk TIA (ABCD2 score ≥4) who did not receive IVT, DAPT (aspirin and clopidogrel with loading dose of clopidogrel) should be initiated early (within 24 hours after symptom onset) and continued for 21 days, followed by single antiplatelet therapy (SAPT) to reduce the 90-day risk of recurrent ischemic stroke. ( 1, A )
13. In patients with recent (<24 hours) minor (NIHSS score ≤5) noncardioembolic AIS or high-risk TIA (ABCD2 score ≥6 or symptomatic intracranial or extracranial ≥50% stenosis of an artery that could account for TIA) who did not receive IVT, DAPT with ticagrelor (including loading dose) plus aspirin for 30 days may be considered to reduce the risk of 30-day recurrent stroke. ( 2b, B-R )
14. (New and of High Impact) In patients with minor (NIHSS score ≤5) noncardioembolic AIS or high-risk TIA (ABCD2 score ≥4) within 24 to 72 hours from stroke onset, or NIHSS score of 4 to 5 within 24 hours from onset, who did not receive IVT, with presumed atherosclerotic cause (≥50% stenosis of intracranial or extracranial stenosis that was likely to have accounted for clinical presentation or acute new infarctions on imaging of presumed large artery atherosclerosis origin), DAPT (clopidogrel and aspirin) for 21 days followed by SAPT is reasonable to reduce the 90-day risk of recurrent stroke. ( 2a, B-R )
15. In patients with minor (NIHSS score ≤3) noncardioembolic AIS or high-risk TIA (ABCD2 score ≥4) within 24 hours after symptom onset who did not receive IVT and who carry the CYP2C19 loss-of-function allele, DAPT with ticagrelor and aspirin for 21 days (followed by ticagrelor monotherapy) may be reasonable in preference over DAPT with clopidogrel and aspirin to reduce the 90-day risk of recurrent stroke. ( 2b, B-R )
Antiplatelet Therapy in the Setting of IVT
16. In patients with AIS who are otherwise eligible for IVT or mechanical thrombectomy, aspirin is not recommended as a substitute for acute stroke treatment to improve patient outcomes. ( 3 - Harm, B-R )
17. In patients with AIS who are eligible for IVT, IV aspirin should not be administered concurrently or within 90 minutes after the start of IVT given the risk of hemorrhage. ( 3 - Harm, B-R )
18. In patients with AIS treated with IVT within 3 hours after symptom onset, adjunctive treatment with IV eptifibatide is not recommended to reduce disability at 3 months. ( 3 - No Benefit, B-R )
Table 7. DAPT Trials
| AIS DAPT trial | Inclusion | Drug/duration | LKN | NNT |
|---|---|---|---|---|
| CHANCE | AIS (NIHSS ≤3) or TIA (ABCD ≥4) | Clopidogrel (300 mg load then 75 mg/d) + Asa (75 mg) × 21 d followed by clopidogrel | 24 h | 28 |
| POINT* | AIS (NIHSS ≤3) or TIA (ABCD ≥4) | Clopidogrel (600 mg load then 75 mg/d) + Asa (50–325 mg/d) × 90 d | 12 h | 67 |
| THALES* | AIS (NIHSS ≤5) or TIA (ABCD ≥6) | Ticagrelor (180 mg load then 90 mg twice daily) + Asa (300–325 mg load then 75–100 mg/d) × 30 d | 24 h | 91 |
| CHANCE 2* | AIS (NIHSS ≤3) or TIA (ABCD ≥4) and CYP2C19 loss-of-function allele | Ticagrelor (180 mg load then 90 mg twice daily) + Asa (75–300 mg load then 75mg/d) × 21 d followed by ticagrelor | 24 h | 63 |
| INSPIRES | AIS (NIHSS ≤5) or TIA (ABCD ≥4), presumed athero | Clopidogrel (300 mg load then 75 mg/d) + Asa (100–300 mg load then 100mg/d) × 21 d followed by clopidogrel | 72 h | 53 |
*Slight increased risk of bleeding.
ABCD indicates Age, Blood Pressure, Clinical Features, Duration (TIA risk score); AIS, acute ischemic stroke; Asa, aspirin; athero, atherosclerosis; CHANCE, Clopidogrel in High-risk patients with Acute Nondisabling Cerebrovascular Events; CHANCE 2, Clopidogrel versus Ticagrelor in High-risk Patients with Acute Nondisabling Cerebrovascular Events; DAPT, Dual Antiplatelet Therapy; INSPIRES, Innovative Stroke Prevention and Intervention Research Study; LKN, last known normal; NIHSS, National Institutes of Health Stroke Scale; NNT, number needed to treat; POINT, Platelet-Oriented Inhibition in New TIA and Minor Ischemic Stroke; THALES, Acute Stroke or Transient Ischemic Attack Treated with Ticagrelor and ASA for Prevention of Stroke and Death; and TIA, transient ischemic attack.
ABCD indicates Age, Blood Pressure, Clinical Features, Duration (TIA risk score); AIS, acute ischemic stroke; Asa, aspirin; athero, atherosclerosis; CHANCE, Clopidogrel in High-risk patients with Acute Nondisabling Cerebrovascular Events; CHANCE 2, Clopidogrel versus Ticagrelor in High-risk Patients with Acute Nondisabling Cerebrovascular Events; DAPT, Dual Antiplatelet Therapy; INSPIRES, Innovative Stroke Prevention and Intervention Research Study; LKN, last known normal; NIHSS, National Institutes of Health Stroke Scale; NNT, number needed to treat; POINT, Platelet-Oriented Inhibition in New TIA and Minor Ischemic Stroke; THALES, Acute Stroke or Transient Ischemic Attack Treated with Ticagrelor and ASA for Prevention of Stroke and Death; and TIA, transient ischemic attack.
4.9. Anticoagulants
1. (New and of High Impact) In carefully selected (eg, milder severity) patients with AIS with atrial fibrillation, a strategy of early oral anticoagulation poststroke is low risk and is reasonable compared with a strategy of delayed anticoagulation, although the efficacy of early anticoagulation for prevention of early recurrent stroke is not established. ( 2a, A )
2. In patients with an AIS and ipsilateral, high-grade ICA stenosis, the benefit of urgent anticoagulation is not well established. ( 2b, B-NR )
3. In patients with AIS with an ipsilateral, nonocclusive, extracranial intraluminal thrombus, the safety and efficacy of short-term anticoagulation are not well established. ( 2b, C-LD )
4. In patients with AIS who experience HT, initiation or continuation of anticoagulation may be considered depending on the specific clinical scenario and underlying indication. ( 3 - No Benefit, C-LD )
5. In patients with AIS, the use of argatroban is not effective as an adjunctive therapy with IVT to improve long-term functional outcomes. ( 3 - No Benefit, A )
6. In patients with AIS, early anticoagulation (within 48 hours of stroke onset) does not reduce the likelihood of early neurological worsening or increase the likelihood of a favorable functional outcome and is not recommended. ( 3 - No Benefit, A )
Figure 4. DAPT for Minor Noncardioembolic AIS and TIA
ABCD2 indicates Age, Blood Pressure, Clinical Features, Duration, and Diabetes (TIA risk score); AIS, acute ischemic stroke; Asa, aspirin; Athero, atherosclerosis; CHANCE, Clopidogrel in High-risk patients with Acute Nondisabling Cerebrovascular Events; CHANCE 2, Clopidogrel versus Ticagrelor in High-risk Patients with Acute Nondisabling Cerebrovascular Events; DAPT, Dual Antiplatelet Therapy; INSPIRES, Innovative Stroke Prevention and Intervention Research Study; LKN, last known normal; MT, mechanical thrombectomy; NIHSS, National Institutes of Health Stroke Scale; POINT, Platelet-Oriented Inhibition in New TIA and Minor Ischemic Stroke; SAPT, Single Antiplatelet Therapy; THALES, Acute Stroke or Transient Ischemic Attack Treated with Ticagrelor and ASA for Prevention of Stroke and Death; and TIA, transient ischemic attack.
4.10. Volume Expansion/Hemodilution, Vasodilators, and Hemodynamic Augmentation
1. In patients with AIS, hemodynamic augmentation using hemodilution, high-dose albumin, or chemical vasodilators such as pentoxifylline is not recommended to improve functional clinical outcomes. ( 3 - No Benefit, A )
2. In patients with AIS, mechanical hemodynamic augmentation with counterpulsation devices or sphenopalatine ganglion stimulation is not recommended to improve functional clinical outcomes. ( 3 - No Benefit, B-R )
4.11. Neuroprotective Agents
1. At present, in patients with AIS, the use of pharmacological or nonpharmacological neuroprotective treatments is not recommended to improve functional outcome. ( 3 - No Benefit, A )
4.12. Emergency Carotid Endarterectomy, Carotid Angioplasty, and Stenting Without Intracranial Clot
1. In patients with AIS or unstable neurological status (eg, stroke in evolution) caused by a high-grade carotid stenosis or occlusion without intracranial occlusion, emergent carotid endarterectomy (within 48 hours) is not beneficial to improve functional outcomes. ( 3 - No Benefit, B-NR )
In-Hospital Management of AIS: General Supportive Care
5.1. Stroke Units
1. In patients with AIS of all ages, treatment within an organized inpatient stroke care unit supported by a specialty trained, interdisciplinary care team (ie, acute stroke units, rehabilitation stroke units, comprehensive stroke units, and mixed rehabilitation units) that incorporates standardized stroke care order sets and protocols is recommended to reduce the odds of poor outcomes and death. ( 1, B-R )
Figure 5. Characteristics of an Organized Specialized Inpatient Care Unit: Flow Diagram
5.2. Dysphagia
1. In patients with AIS, performing a bedside swallow screening prior to initiation of liquid or food intake is recommended to screen for patients at increased risk for aspiration. ( 1, C-EO )
2. In patients with AIS, it is reasonable for dysphagia screening to be performed by speech pathologists or other trained health care professionals. ( 2a, C-LD )
3. In patients with AIS who have failed or are unable to participate in a bedside swallow screening due to neurological disabilities, it is reasonable to perform instrumental swallowing assessment, including flexible endoscopic evaluation of swallowing or videofluoroscopic swallow study, to aid in determination of dysphagia severity and aspiration risk. ( 2a, B-NR )
4. In patients with AIS, an oral hygiene protocol may be reasonable to reduce the risk for pneumonia. ( 2b, B-NR )
5. (New and of High Impact) In non-tracheostomized patients with stroke and dysphagia, treatment with pharyngeal electrical stimulation (PES) may be reasonable to improve swallowing function, as assessed by radiological or instrumental swallowing evaluation and clinical dysphagia scales. ( 2b, B-R )
6. In patients with severe stroke with dysphagia requiring tracheotomy and mechanical ventilation, treatment with PES after ventilator weaning is reasonable to facilitate readiness for decannulation, as determined by flexible endoscopic evaluation of swallowing. ( 2a, B-R )
5.3. Nutrition
1. In patients with AIS, enteral diet should be started within 7 days of admission after an AIS. ( 1, B-R )
2. In patients with AIS, nutritional screening is recommended to direct nutritional management early into hospitalization, preferably within 48 hours of admission, with a nutritional screening or assessment tool that has been validated in patients with acute stroke. ( 1, B-NR )
3. In patients with AIS with dysphagia, it is reasonable to use nasogastric tubes initially for feeding within the first 7 days and to place percutaneous gastrostomy tubes in patients with longer anticipated persistent inability to swallow safely (>2–3 weeks). ( 2a, B-NR )
5.4. Deep Vein Thrombosis Prophylaxis
1. In patients with AIS who have impaired mobility and do not have contraindications to intermittent pneumatic compression (IPC), IPC in addition to routine care is recommended over routine care alone to reduce the risk of deep vein thrombosis (DVT). ( 1, B-R )
2. In patients with AIS who have impaired mobility, either prophylactic-dose subcutaneous heparin (UFH or LMWH) is reasonable to reduce the risk of VTE. ( 2a, B-R )
4. In patients with AIS who have impaired mobility and who are selected for prophylactic anticoagulation, the benefit of prophylactic-dose LMWH over prophylactic-dose UFH to prevent DVT is uncertain. ( 2b, B-R )
5. In patients with AIS who have impaired mobility, elastic compression stockings cause harm, including skin breakdown, ulceration, and tissue necrosis, compared with usual care. ( 3 - Harm, B-R )
5.5. Depression
1. In patients with AIS, administration of a structured depression inventory is recommended to routinely screen for poststroke depression (PSD), although the optimal timing of screening is uncertain. ( 1, B-NR )
2. In patients diagnosed with PSD, treatment with antidepressants and/or nonpharmacological interventions (ie, psychotherapy, noninvasive brain stimulation, acupuncture) is recommended to improve depressive symptoms. ( 1, B-R )
5.6. Other In-Hospital Management Considerations
1. For select patients with AIS and their families, referral to palliative care resources is reasonable as appropriate. ( 2a, C-EO )
2. In patients with AIS, routine use of prophylactic antibiotics has not been shown to be beneficial in improving functional outcomes. ( 3 - No Benefit, A )
3. In patients with AIS, routine placement of indwelling bladder catheters should not be performed because of the associated risk of catheter-associated urinary tract infections (UTIs). ( 3 - Harm, C-LD )
5.7. Rehabilitation
1. In patients with AIS, in-hospital, formal, interdisciplinary assessment and provision of rehabilitation at a level appropriate for the individual patient is recommended to improve functional recovery. ( 1, A )
2. In patients with AIS, SSRIs are not effective for improving motor recovery or functional status. ( 3 - No Benefit, A )
3. In patients with AIS, high-dose, very early mobilization within 24 hours of stroke onset is not recommended to improve the odds of a favorable outcome at 3 months and may be harmful. ( 3 - Harm, B-R )
In-Hospital Management of AIS: Treatment of Acute Complications
6.1. Brain Swelling (General Recommendations)
1. In patients with large cerebral or cerebellar infarctions at high risk for developing brain swelling and herniation, an early discussion of care options and possible outcomes should take place with patients (if feasible) and family or next of kin to ascertain patient-centered preferences in shared decision making, especially during prognosis formation and when considering interventions or limitations in care. ( 1, C-EO )
2. In patients with large cerebral or cerebellar infarctions, close monitoring of the patient for signs of neurological worsening during the first days after stroke is recommended to rapidly evaluate the need for potential interventions. ( 1, C-EO )
3. In patients with large cerebral or cerebellar infarctions who are at increased risk for malignant brain swelling, early transfer to an institution with appropriate neurosurgical and critical care expertise is recommended to ensure timely treatment. ( 1, C-LD )
6.2. Brain Swelling (Medical Management)
1. In patients with large cerebral or cerebellar infarctions and neurological decline from brain swelling, the use of osmotic therapy as a bridge to a surgical intervention is reasonable to improve functional outcome and reduce mortality. ( 2a, C-LD )
2. (New and of High Impact) In patients with large hemispheric infarction aged 18 to 70 years, the use of IV glibenclamide does not result in improved functional outcome and is not recommended. ( 3 - No Benefit, B-R )
3. In patients with large cerebral or cerebellar infarctions and brain swelling, hypothermia, barbiturates, or corticosteroids should not be administered to treat brain swelling due to the lack of evidence of efficacy and potential of increased adverse effects. ( 3 - Harm, C-LD )
6.3. Supratentorial Infarction (Surgical Management)
1. In patients with large territorial cerebral infarctions at high risk for developing brain swelling and herniation, decreased level of consciousness attributed to brain swelling is a reasonable trigger for decompressive hemicraniectomy selection. ( 2a, B-NR )
2. In patients ≤60 years of age with unilateral MCA infarctions who deteriorate neurologically within 48 hours from brain swelling despite medical therapy, decompressive craniectomy with dural expansion is beneficial to reduce mortality and improve functional outcome. ( 1, A )
3. In patients >60 years of age with unilateral MCA infarctions who deteriorate neurologically within 48 hours from brain swelling despite medical therapy, decompressive craniectomy with dural expansion may be considered to reduce mortality. ( 2b, B-R )
4. In patients with AIS who received IV tPA thrombolysis and develop malignant cerebral edema despite medical therapy, early decompressive craniectomy within 48 hours may still be considered without additional safety concerns. ( 2b, B-NR )
6.4. Cerebellar Infarction (Surgical Management)
1. In patients with cerebellar infarction and obstructive hydrocephalus, ventriculostomy is recommended to improve neurological function and decrease mortality. Concomitant or subsequent decompressive craniectomy may or may not be necessary on the basis of factors such as the size of the infarction, neurological condition, degree of brainstem compression, and effectiveness of medical management. ( 1, C-LD )
2. In patients with cerebellar infarction causing neurological deterioration from brainstem compression or volumes ≥35 mL, decompressive suboccipital craniectomy with dural expansion should be performed to improve outcomes and decrease mortality. ( 1, B-R )
6.5. Seizures
1. In adult patients with an unprovoked seizure after AIS, management that includes antiseizure medication is recommended on the basis of specific patient characteristics to reduce the risk of seizure recurrence. ( 1, C-LD )
2. In adult patients with AIS, prophylactic treatment with antiseizure medication is not recommended to prevent seizures or improve functional outcome. ( 3 - No Benefit, C-LD )
Class of Recommendations and Level of Evidence
| Class (Strength) of Recommendation |
|---|
| CLASS 1 (STRONG) Benefit >>> Risk |
Suggested phrases for writing recommendations:
|
| CLASS 2a (MODERATE) Benefit >> Risk |
Suggested phrases for writing recommendations:
|
| CLASS 2b (WEAK) Benefit ≥ Risk |
Suggested phrases for writing recommendations:
|
| CLASS 3: No Benefit (MODERATE) (Generally, LOE A or B use only) Benefit = Risk |
Suggested phrases for writing recommendations:
|
| CLASS 3: Harm (STRONG) Risk > Benefit |
Suggested phrases for writing recommendations:
|
| Level (Quality) of Evidence‡ |
|---|
| LEVEL A |
|
| LEVEL B-R (Randomized) |
|
| LEVEL B-NR (Nonrandomized) |
|
| LEVEL C-LD (Limited Data) |
|
| LEVEL C-EO (Expert Opinion) |
|
COR and LOE are determined independently (any COR may be paired with any LOE).
A recommendation with LOE C does not imply that the recommendation is weak. Many important clinical questions addressed in guidelines do not lend themselves to clinical trials. Although RCTs are unavailable, there may be a very clear clinical consensus that a particular test or therapy is useful or effective.
* The outcome or result of the intervention should be specified (an improved clinical outcome or increased diagnostic accuracy or incremental prognostic information).
† For comparative-effectiveness recommendations (COR I and IIa; LOE A and B only), studies that support the use of comparator verbs should involve direct comparisons of the treatments or strategies being evaluated.
‡ The method of assessing quality is evolving, including the application of standardized, widely used, and preferably validated evidence grading tools; and for systematic reviews, the incorporation of an Evidence Review Committee.
COR indicates Class of Recommendation; EO, expert opinion; LD, limited data; LOE, Level of Evidence; NR, nonrandomized; R, randomized; RCT, randomized controlled trial.
Abbreviations
- ABCD
- Age, Blood Pressure, Clinical Features, Duration, and Diabetes (TIA risk score)
- ACC
- American College of Cardiology
- AF
- atrial fibrillation
- AHA
- American Heart Association
- AIS
- Acute Ischemic Stroke
- AKI
- acute kidney injury
- ARD
- Absolute risk difference
- ASA
- aspirin
- ASA
- American Stroke Association
- ASCVD
- atherosclerotic cardiovascular disease
- ASPECTS
- Alberta Stroke Program Early Computed Tomography Score
- ASRH
- acute stroke-ready hospital
- Athero
- atherosclerosis
- BP
- blood pressure
- CBF
- cerebral blood flow
- CEA
- carotid endarterectomy
- CeAD
- Cervical artery dissection
- CHANCE
- Clopidogrel in High-risk patients with Acute Nondisabling Cerebrovascular Events
- CHANCE 2
- Clopidogrel versus Ticagrelor in High-risk Patients with Acute Nondisabling Cerebrovascular Events
- CMB
- Cerebral microbleed
- COR
- Class of Recommendation
- CPAP
- continuous positive airway pressure
- CRAO
- central retinal artery occlusion
- CS
- Conscious sedation
- CSC
- comprehensive stroke center
- CSF
- cerebrospinal fluid
- CT
- computed tomography
- CTA
- computed tomography angiography
- CTA
- computed tomographic angiography
- CTP
- Computed tomographic perfusion
- DAPT
- dual antiplatelet therapy
- DBP
- diastolic blood pressure
- DIDO
- door-in-door-out
- DOAC
- direct oral anticoagulants
- DSM
- Diagnostic and Statistical Manual of Mental Disorders
- DTAS
- direct triage to the angiography suite
- DTN
- Door-to-needle
- DVT
- deep vein thrombosis
- DW-MRI
- Diffusion-weighted magnetic resonance imaging
- DWI
- diffusion-weighted imaging
- ECG
- electrocardiogram
- ED
- emergency department
- EMS
- emergency medical services
- EVT
- endovascular thrombectomy
- EVT
- endovascular therapy
- FLAIR
- fluid attenuated inversion recovery
- GA
- General anesthesia
- GPC
- graded compression stockings
- GTN
- glyceryl trinitrate
- GWTG
- Get with the guidelines
- HBO
- hyperbaric oxygen
- HR
- hazard ratio
- HT
- Hemorrhagic transformation
- ICA
- internal carotid artery
- ICH
- intracerebral hemorrhage
- ICU
- intensive care unit
- INSPIRES
- Innovative Stroke Prevention and Intervention Research Study
- IPC
- intermittent pneumatic compression
- IV
- intravenous
- IVT
- intravenous thrombolytics
- LDL-C
- low density lipoprotein-cholesterol
- LKN
- last known normal
- LMWH
- last known normal
- LMWH
- low molecular weight heparin
- LOE
- Level of Evidence
- LVO
- Large vessel occlusion
- M1
- Middle cerebral artery segment 1
- M2
- Middle cerebral artery segment 2
- M3
- Middle cerebral artery segment 3
- MCA
- Middle cerebral artery
- MI
- myocardial infarction
- MR
- magnetic resonance
- MRA
- Magnetic resonance angiography
- MRI
- magnetic resonance imaging
- mRS
- Modified Rankin Scale
- mRS
- magnetic resonance angiography
- MSU
- mobile stroke unit(s)
- mTICI
- Modified Thrombolysis in Cerebral Infarction
- NBO
- normobaric hyperoxia
- NCCT
- Noncontrast computed tomogrphy
- NIHSS
- National Institutes of Health Stroke Scale
- NINDS
- National Institute of Neurological Disorders and Stroke
- NIRS
- near-infrared spectroscopy
- OR
- odds ratio
- OSA
- obstructive sleep apnea
- PE
- pulmonary embolism
- PES
- pharyngeal electrical stimulation
- PFO
- patent foramen ovale
- PSC
- primary stroke center
- PSD
- poststroke depression
- QI
- quality improvement
- RCT
- randomized clinical trial
- RR
- relative risk
- rt-PA
- Recombinant tissue-type plasminogen activator
- SAE
- serious adverse event
- SAPT
- single antiplatelet therapy
- SBP
- systolic blood pressure
- sICH
- Symptomatic intracerebral hemorrhage
- SpO2
- oxygen saturation
- SSOC
- stroke systems of care
- SSRI
- selective serotonin reuptake inhibitor
- THALES
- Acute Stroke or Transient Ischemic Attack Treated with Ticagrelor and ASA for Prevention of Stroke and Death
- TIA
- transient ischemic attack
- tPA
- Tissue plasminogen activator
- TSC
- thrombectomy-capable stroke center
- UFH
- unfractionated heparin
- UTI
- urinary tract infection
- VTE
- venous thromboembolism
Source Citation
Prabhakaran, Shyam et al. “2026 Guideline for the Early Management of Patients With Acute Ischemic Stroke: A Guideline From the American Heart Association/American Stroke Association.” Stroke, 10.1161/STR.0000000000000513. 26 Jan. 2026, doi:10.1161/STR.0000000000000513
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