What are the key recommendations of the 2026 American Heart Association/American Stroke Association guideline for the early management of acute ischemic stroke?

2026 American Heart Association/American Stroke Association Guideline for Early Management of Acute Ischemic Stroke

The 2026 AHA/ASA guideline, published in March 2025, represents the most current comprehensive evidence-based framework for acute ischemic stroke management, replacing the 2018 guideline and incorporating critical advances in thrombolytic selection, endovascular thrombectomy eligibility, and pediatric considerations. 1

Prehospital Transport and System Organization

Emergency medical services must bypass hospitals lacking stroke-treatment capabilities and transport patients directly to certified Primary Stroke Centers or Comprehensive Stroke Centers. 2 This Class I, Level B recommendation ensures patients reach facilities capable of delivering time-sensitive interventions. 2

• Certification should be performed by independent external bodies such as The Joint Commission or state health departments. 2
• For facilities without in-house imaging interpretation, FDA-approved teleradiology systems enable rapid CT/MRI review. 2
• Prehospital notification allows the stroke team to prepare before patient arrival, reducing door-to-needle times. 3

Emergency Department Triage and Initial Assessment

Patients with suspected acute stroke must be triaged with the same urgency as acute myocardial infarction or severe trauma, regardless of neurological deficit severity. 2 This Class I, Level B recommendation reflects stroke's time-dependent nature. 2

Immediate Stabilization

• Airway, breathing, and circulation stabilization takes precedence over other assessments. 2
• Maintain oxygen saturation >94% using supplemental oxygen only when needed. 3, 4
• Obtain fingerstick glucose immediately to exclude hypoglycemia as a stroke mimic. 3

Critical Time Targets

• Emergency brain imaging interpretation within 45 minutes of arrival. 4
• Door-to-needle time <60 minutes for ≥90% of thrombolysis candidates. 2
• Every 15-minute reduction in door-to-needle time decreases in-hospital mortality by 5%; every 30-minute delay reduces favorable outcome probability by approximately 10.6%. 2, 3

Stroke Mimics to Exclude

The guideline emphasizes ruling out key mimics before committing to stroke-specific therapy: 5, 3

• Hypoglycemia: Check glucose in all patients, especially those with diabetes history
• Seizure with Todd's paralysis: Witnessed seizure activity followed by transient deficit
• Complicated migraine: Prior similar episodes with aura and headache
• Hypertensive encephalopathy: Severe headache, delirium, markedly elevated BP, cortical blindness
• Psychogenic causes and drug toxicity: Behavioral assessment and toxicology screening when indicated

Diagnostic Imaging Protocol

Non-contrast CT brain must be obtained immediately to exclude intracerebral hemorrhage before initiating thrombolysis. 2 This Class I, Level A recommendation is absolute. 2

Vascular Imaging

• CT angiography should be performed without delay to identify large-vessel occlusion (internal carotid, M1/M2 MCA, basilar artery). 2 This Class I, Level A recommendation applies to all patients within the thrombectomy window. 2
• CT perfusion may be added in selected cases to assess penumbra, but never delay thrombolysis to obtain advanced multimodal imaging. 3 This is a Class III, Level B recommendation against delaying treatment. 3

Laboratory Testing

Essential tests include: 5

• Blood glucose (immediate)
• Oxygen saturation
• Complete blood count with platelets
• Serum electrolytes and renal function
• Prothrombin time/INR and aPTT
• Markers of cardiac ischemia
• ECG to assess cardiac rhythm 4

Fibrinolytic therapy should not be delayed awaiting laboratory results unless there is clinical suspicion of bleeding abnormality, thrombocytopenia, or the patient has received anticoagulants. 5

Intravenous Thrombolysis

The 2026 guideline confirms intravenous alteplase 0.9 mg/kg (maximum 90 mg) as the single most critical intervention for acute ischemic stroke, administered within 3-4.5 hours of symptom onset. 2, 3 This Class I, Level A recommendation reflects decades of evidence showing 37% of guideline-adherent patients achieve full functional independence. 3

Dosing and Administration

• 10% of total dose given as IV bolus over 1 minute, remaining 90% infused over 60 minutes. 2, 3
• The 3-4.5 hour window reflects ECASS-3 trial data extending treatment beyond the original 3-hour window. 2
• Treatment beyond 4.5 hours is not recommended. 3

Blood Pressure Requirements for Thrombolysis

Blood pressure must be lowered to <185/110 mmHg BEFORE starting alteplase and maintained ≤180/105 mmHg during infusion and for 24 hours post-treatment. 2, 3, 4 This Class I, Level A requirement is absolute; patients who cannot achieve this target are ineligible. 3

Key Updates in 2026 Guideline

The 2026 guideline incorporates new evidence on thrombolytic choice and eligibility criteria, though specific details on tenecteplase versus alteplase selection await full guideline publication. 1, 6 Tenecteplase has emerged as an alternative thrombolytic with potential advantages in ease of administration. 6

Post-Thrombolysis Monitoring

Neurological status and vital signs must be checked every 15 minutes during and for 2 hours after alteplase, then every 30 minutes for 6 hours, and hourly until 24 hours post-treatment. 2, 3 This Class I, Level B recommendation enables early detection of hemorrhagic complications. 2

• Symptomatic intracranial hemorrhage occurs in approximately 6.4% of rtPA-treated patients. 2
• Protocol violations markedly increase symptomatic ICH risk and mortality. 3

Endovascular Thrombectomy

The 2026 guideline specifies that mechanical thrombectomy with stent-retriever devices is indicated when ALL of the following criteria are met: prestroke mRS 0-1, confirmed large-vessel occlusion on CTA, age ≥18 years, NIHSS ≥6, ASPECTS ≥6, and groin puncture ≤6 hours from onset. 2, 3 This Class I, Level A recommendation is based on five landmark 2015 trials (MR CLEAN, ESCAPE, SWIFT-PRIME, EXTEND-IA, REVASCAT). 2, 3

Critical Workflow Principles

• IV alteplase must be administered first and should not be delayed while preparing for EVT; both therapies are complementary. 2, 3 This Class I, Level A recommendation emphasizes that thrombolysis and thrombectomy are not mutually exclusive. 2
• Do not wait for clinical response to IV rtPA before initiating EVT; delaying thrombectomy worsens outcomes. 2 This Class III, Level B-R recommendation reflects evidence that every minute counts. 2

Technical Considerations

• Stent retrievers (Solitaire FR, Trevo) are preferred over older coil retrievers. 2, 3
• Use of proximal balloon-guide catheter or large-bore distal-access catheter with stent retriever improves recanalization rates. 2
• Target final angiographic result of TICI 2b/3, associated with highest likelihood of good functional outcome. 2

Extended Time Windows

Selected patients meeting specific imaging and clinical thresholds may be treated up to 12 hours after onset. 3 The 2026 guideline includes updated criteria for determining eligibility in extended windows. 1

Intra-Arterial Thrombolysis

For patients with major middle-cerebral-artery occlusion presenting <6 hours after onset who are ineligible for IV alteplase, intra-arterial thrombolysis may be considered at comprehensive stroke centers with immediate angiography capability. 3 This Class I, Level C recommendation applies to patients with contraindications such as recent surgery. 3

• Delivery requires qualified interventionalists and comprehensive stroke-center infrastructure. 3
• Availability of intra-arterial therapy should not preclude IV alteplase in eligible patients. 3, 4

Blood Pressure Management in Non-Thrombolysis Candidates

For patients NOT receiving thrombolysis, adopt permissive hypertension unless systolic >220 mmHg or diastolic >120 mmHg. 3 This Class III, Level A recommendation reflects evidence that aggressive lowering impairs penumbral perfusion. 3

• Initiating antihypertensives within 48-72 hours when BP <220/120 mmHg does not reduce death or dependency. 3
• When BP ≥220/120 mmHg, a modest reduction of approximately 15% during the first 24 hours may be considered, though benefit is uncertain (Class IIb, Level C). 3

This represents a critical divergence from thrombolysis candidates and is a common source of error in acute stroke management. 3

Antiplatelet Therapy

Delay aspirin initiation for at least 24 hours after IV rtPA until post-treatment CT excludes intracranial hemorrhage; then start aspirin 150-325 mg daily. 2, 3 This Class I, Level A recommendation balances recurrent stroke prevention against hemorrhage risk. 2

Timing and Dosing

• Never administer antiplatelet agents within 24 hours of rtPA due to increased bleeding risk. 2, 3
• For patients NOT receiving thrombolysis, give aspirin 325 mg within 24-48 hours of stroke onset. 2, 3, 4
• Aspirin's primary benefit is reduction of early recurrent stroke rather than mitigation of initial injury. 3

What NOT to Use

• Clopidogrel alone or combined with aspirin is not recommended for acute ischemic stroke (Class III, Level C). 3
• Intravenous glycoprotein IIb/IIIa inhibitors are not recommended outside clinical trials (Class III, Level B). 3
• Do not combine clopidogrel with aspirin for chronic secondary prevention. 3

Anticoagulation in the Acute Phase

Full-dose unfractionated heparin or low-molecular-weight heparin should NOT be used for acute ischemic stroke; they do not improve outcomes and increase hemorrhage risk. 3 This Class III, Level A recommendation from the American College of Chest Physicians reflects consistent trial evidence. 3

• Emergency anticoagulation does not lower early recurrent stroke risk, even in cardioembolic sources. 3
• Anticoagulation does not prevent early neurological worsening. 3
• Most randomized trials have failed to demonstrate functional outcome benefit. 3

Stroke Unit Care and Supportive Management

Admit all patients to a geographically defined stroke unit with specialized nursing staff; stroke-unit care reduces mortality and disability across all stroke types, ages, and severities. 2, 3 This Class I, Level A recommendation reflects evidence that stroke-unit care produces benefits comparable to thrombolysis itself. 3

Early Mobilization

• Begin frequent brief mobilization (sitting, standing, brief ambulation) within 24 hours if no contraindications exist. 2, 3 This Class I, Level B recommendation reduces complications and improves functional outcomes. 3
• Assess swallowing before any oral intake to prevent aspiration. 3

Temperature Management

• Check core temperature every 4 hours for the first 48 hours and treat fever promptly (target ≤37.5°C). 3 This Class I, Level A recommendation reflects evidence that hyperthermia worsens neurological damage. 3
• Identify and treat sources of hyperthermia (>38°C). 2, 4

Glucose Management

The 2026 guideline includes updated recommendations on hyperglycemia management. 1

• Treat hypoglycemia (<60 mg/dL) to achieve normoglycemia. 2
• Treat hyperglycemia to maintain glucose 140-180 mg/dL. 2

Dysphagia Screening

The 2026 guideline incorporates new evidence on dysphagia management. 1 Formal swallowing assessment before oral intake prevents aspiration pneumonia. 3

Venous Thromboembolism Prophylaxis

• Start intermittent pneumatic compression devices within 24 hours for immobile patients. 3 This Class I, Level B recommendation provides mechanical prophylaxis. 3
• When pharmacologic prophylaxis is indicated, use prophylactic-dose LMWH rather than unfractionated heparin. 3

Management of Malignant MCA Syndrome

Perform decompressive hemicraniectomy within 48 hours of symptom onset for patients with malignant cerebral edema. 2 This Class I, Level A recommendation applies to specific criteria. 2

Surgical Criteria

• Infarct >50% of MCA territory or lesion volume >150 cm³
• Radiologic evidence of significant edema/mass effect
• Age 18-60 years (strongest evidence, Class I, Level A)
• Age 60-80 years may be considered (Class I, Level B)

Outcomes

• Decompressive surgery reduces mortality by approximately 50% but most survivors have moderate-to-severe disability (mRS 3-4). 2
• In patients >60 years, surgery lowers mortality but none achieve good functional recovery (mRS 0-2). 2

Medical Management of Edema

• Corticosteroids are NOT recommended for cerebral edema management following ischemic stroke. 4
• Osmotherapy and hyperventilation are recommended for patients deteriorating from increased intracranial pressure. 4

Pediatric Considerations

The 2026 guideline includes a focused consideration of the pediatric population, representing a significant update from prior versions. 1 Specific pediatric protocols for thrombolysis and thrombectomy eligibility are now addressed. 1

Secondary Prevention Initiation

Cardiac Evaluation

• Obtain transthoracic echocardiography to assess cardioembolic sources. 2
• Consider transesophageal echocardiography if source suspected but not identified (Class IIa). 2

Long-Term Antiplatelet Therapy

For ongoing secondary prevention: 3

• Aspirin 75-100 mg daily, OR
• Clopidogrel 75 mg daily, OR
• Aspirin + extended-release dipyridamole (25 mg/200 mg twice daily), OR
• Cilostazol 100 mg twice daily

Clopidogrel or aspirin + extended-release dipyridamole are favored over aspirin alone for reducing recurrent stroke risk. 3

Atrial Fibrillation

In patients with prior stroke/TIA and atrial fibrillation, prescribe oral anticoagulation (warfarin or direct oral anticoagulant) rather than no therapy, aspirin alone, or aspirin + clopidogrel. 3

Lipid and Blood Pressure Control

• Initiate statin therapy for lipid lowering regardless of baseline levels (Class I, Level A). 2
• Begin antihypertensive therapy for long-term blood pressure control before discharge (Class I, Level A). 2

Modified Approach to Thrombolysis Contraindications

The 2026 guideline includes modification of the approach to thrombolysis contraindications, reflecting evolving evidence on relative versus absolute contraindications. 1 This represents a significant update allowing more patients to receive treatment. 1

Quality Improvement and System Metrics

Healthcare institutions should establish a multidisciplinary quality-improvement committee to review stroke-care benchmarks, evidence-based practices, and outcomes. 2, 3 This Class I, Level B recommendation ensures continuous improvement. 2

• Create a stroke-care data bank to identify gaps or disparities in care. 2
• Implement targeted interventions to address identified gaps. 2
• Monitor door-to-needle times, with target median ≤30 minutes and 90th percentile ≤60 minutes. 3

Critical Pitfalls to Avoid

Do not delay thrombolysis for advanced imaging (perfusion/diffusion MRI) when eligibility is established based on non-contrast CT. 2, 3 This Class I, Level B recommendation reflects evidence that imaging delays worsen outcomes. 2

Do not use full-dose anticoagulation (IV or subcutaneous heparin) in acute ischemic stroke; it increases hemorrhage risk without improving outcomes. 2, 3 This Class III, Level B recommendation is absolute. 2

Do not assume behavioral symptoms (confusion, agitation) are contraindications to thrombolysis; they may reflect the stroke itself. 2

Emergency carotid endarterectomy is generally avoided in acute ischemic stroke due to high peri-procedural risk (Class III, Level B). 2

Do not aggressively lower blood pressure in acute stroke unless giving thrombolytics or BP >220/120 mmHg, as permissive hypertension maintains penumbral perfusion. 3

Do not give aspirin as adjunctive therapy with alteplase, and do not delay alteplase for "minor" symptoms, as early treatment is critical even for seemingly mild deficits. 3

Gaps in Knowledge and Future Directions

The 2026 guideline highlights gaps in knowledge and underscores the urgent need for continued research to further refine treatment strategies. 1 Areas requiring additional investigation include optimal patient selection for extended-window therapies, refinement of pediatric protocols, and strategies to improve outcomes in patients with large-core infarcts. 1