2026 AHA/ASA Acute Ischemic Stroke Guideline: Major Shifts in Thrombolysis, EVT, and Systems

The 2026 AHA/ASA guideline replaces the 2018 guideline and its 2019 update, elevating tenecteplase to a co-first-line thrombolytic with alteplase, endorsing imaging-selected thrombolysis out to 9 hours and in wake-up stroke, expanding endovascular thrombectomy to large ischemic cores and basilar occlusion, and reversing intensive glucose and blood-pressure targets.

AHAASAacute ischemic stroketenecteplasealteplaseIV thrombolysisendovascular thrombectomybasilar artery occlusionextended windowwake-up strokeDAPTblood pressure managementglycemic managementmobile stroke unitspediatric stroke Ischemic Stroke

Authors: Prabhakaran S, Gonzalez NR, Zachrison KS, Adeoye O, Alexandrov AW, Ansari SA, Chapman S, Czap AL, Dumitrascu OM, Ishida K, Jadhav AP, Johnson B, Johnston KC, Khatri P, Kimberly WT, Lee VH, Leslie-Mazwi TM, Mac Grory B, Madsen TE, Menon B, Mistry EA, Park S, Parker S, Pérez de la Ossa N, Reeves M, Saiz T, Scott PA, Schwartzberg D, Sheth SA, Sporns PB, Times S, Tjoumakaris S, Wolfe SQ, Yaghi S, Peer Review Committee

Citation: Prabhakaran S, Gonzalez NR, Zachrison KS, 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. 2026. doi:10.1161/STR.0000000000000513

Article Links: PubMed · Journal / DOI

🎓

Reviewed by a licensed pharmacist

Every analysis is reviewed and approved by a licensed pharmacist before publication, ensuring clinical accuracy and relevance.

Accurate and up-to-date information is our highest priority.

If you spot an error, please suggest a correction. If there is a topic you want covered, tell us and we will look at it.

Suggest a correction Request a topic

Practice-changing Impact 3/5

This guideline expands core thrombolysis, EVT, and critical care elements, mandating foundational updates for stroke pharmacists' protocols.

Evidence Grade: High

Core thrombolysis and thrombectomy recommendations rest on multiple multicenter randomized controlled trials; several supportive-care reversals (glucose, blood pressure, adjuvant antithrombotics) are also RCT-based.

⚡ Bottom Line

Tenecteplase 0.25 mg/kg is now an equal first-line thrombolytic to alteplase within 4.5 hours, thrombolysis extends to 4.5-9 hours and wake-up stroke with perfusion or DWI-FLAIR mismatch selection, thrombectomy expands to large cores (ASPECTS 3-5) and basilar occlusion, and intensive glucose (80-130 mg/dL) and blood-pressure (<140 mm Hg) targets are no longer recommended.

What's New / Changed vs. Prior Version

Versus the 2018 guideline and 2019 update: (1) tenecteplase 0.25 mg/kg (max 25 mg) is now recommended on equal footing with alteplase 0.9 mg/kg in the 4.5-hour window (COR 1), rather than only as an alternative for minor stroke or bridging; (2) treatment should proceed without delay for additional CTA/MRA or CT/MR perfusion in the standard 4.5-hour window (COR 1); (3) extended-window IV thrombolysis (4.5-9 hours from last known well, or wake-up within 9 hours of sleep midpoint) is newly endorsed for patients with salvageable penumbra on automated perfusion imaging (COR 2a); (4) endovascular thrombectomy is expanded to selected large-core strokes (ASPECTS 3-5, 6-24 hours, COR 1) and to basilar artery occlusion (NIHSS >=10, PC-ASPECTS >=6, within 24 hours, COR 1); (5) adjuvant argatroban, eptifibatide, and pre-thrombectomy tirofiban are not recommended to enhance reperfusion outcomes (COR 3: No Benefit); (6) intensive IV-insulin control to 80-130 mg/dL is no longer recommended and increases severe hypoglycemia (COR 3: No Benefit); (7) intensive systolic BP lowering to <140 mm Hg is not recommended after IV thrombolysis (COR 3: No Benefit) and is harmful after successful thrombectomy (COR 3: Harm); (8) mobile stroke units are recommended where available (COR 1); and (9) for the first time the guideline includes pediatric acute ischemic stroke recommendations.

Key Recommendations & Class/Level of Evidence

Recommendation	Class	Level
In adults with AIS within 4.5 hours of onset or last known well and eligible for IV thrombolysis, tenecteplase 0.25 mg/kg (max 25 mg) or alteplase 0.9 mg/kg is recommended to improve functional outcomes.	COR 1	Not specified
In adults eligible for IV thrombolysis within 4.5 hours, initiate treatment as quickly as possible without delaying for additional multimodal imaging (CTA/MRA, CT/MR perfusion).	COR 1	Not specified
In patients with salvageable penumbra on automated perfusion imaging who wake with stroke symptoms (within 9 hours of sleep midpoint) or are 4.5-9 hours from last known well, IV thrombolysis may be reasonable.	COR 2a	Not specified
In minor (NIHSS <=5) noncardioembolic AIS or high-risk TIA of presumed atherosclerotic cause not receiving thrombolysis, DAPT (clopidogrel plus aspirin) for 21 days followed by single antiplatelet therapy is reasonable to reduce 90-day recurrent stroke.	COR 2a	Not specified
Adjuvant argatroban or eptifibatide given concurrently with IV thrombolysis is not recommended, as it does not improve outcomes.	COR 3: No Benefit	Not specified
Preoperative administration of tirofiban before endovascular thrombectomy is not useful to improve 90-day functional outcome.	COR 3: No Benefit	Not specified
In carefully selected (eg, milder severity) patients with AIS and atrial fibrillation, early oral anticoagulation is low risk and reasonable compared with delayed anticoagulation.	COR 2a	Not specified
In hospitalized patients with AIS and hyperglycemia, IV insulin targeting 80-130 mg/dL is not recommended to improve 3-month outcomes and increases severe hypoglycemia.	COR 3: No Benefit	Not specified
In mild-to-moderate AIS treated with IV thrombolysis, intensive systolic BP reduction (<140 vs <180 mm Hg) is not recommended.	COR 3: No Benefit	Not specified
In anterior-circulation LVO successfully recanalized by thrombectomy (mTICI 2b-3), intensive systolic BP reduction to <140 mm Hg for 72 hours is harmful and not recommended.	COR 3: Harm	Not specified
In basilar artery occlusion with baseline mRS 0-1, NIHSS >=10, and PC-ASPECTS >=6 within 24 hours, endovascular thrombectomy is recommended to improve outcomes and reduce mortality.	COR 1	Not specified
In selected anterior-circulation LVO (ICA/M1) 6-24 hours from onset with ASPECTS 3-5 (large core), endovascular thrombectomy is recommended to improve functional outcomes and reduce mortality.	COR 1	Not specified
Where available, mobile stroke units are recommended over conventional EMS for transport and management of thrombolytic-eligible patients to shorten onset-to-treatment time.	COR 1	Not specified

Practice Impact for Pharmacists

Add tenecteplase 0.25 mg/kg (max 25 mg) as an equal first-line thrombolytic in stroke order sets; its single IV bolus simplifies administration, transfer, and door-to-needle workflow versus the alteplase infusion.
Update thrombolysis protocols so treatment in the 4.5-hour window is not delayed to obtain CTA/MRA or perfusion imaging.
Build or support extended-window (4.5-9 hour and wake-up) thrombolysis pathways that depend on automated perfusion or DWI-FLAIR mismatch selection.
Revise post-thrombolysis and post-thrombectomy blood-pressure order sets away from intensive <140 mm Hg targets (no benefit after IVT; harm after successful EVT).
Retire intensive IV-insulin protocols targeting 80-130 mg/dL in stroke; maintain moderate glycemic control to avoid hypoglycemia.
De-adopt adjuvant argatroban, eptifibatide, and pre-thrombectomy tirofiban used to enhance reperfusion outcomes.
Operationalize 21-day DAPT (clopidogrel plus aspirin) then single antiplatelet therapy for eligible minor noncardioembolic stroke or high-risk TIA.
Facilitate earlier DOAC initiation in carefully selected milder AIS with atrial fibrillation, coordinating timing with the stroke team.

Implementation Considerations

Realizing these changes is largely a pharmacy-and-protocol exercise: P&T review to formalize tenecteplase (0.25 mg/kg) as co-first-line despite its off-label status for stroke in some jurisdictions, weight-based dosing safeguards and max-dose (25 mg) hard stops in the EHR, revised BP and glucose order sets, and staff education for ED and stroke teams. Extended-window and large-core pathways require reliable access to automated perfusion software and clear imaging-selection criteria.

Controversies / Dissenting Opinions

Tenecteplase co-first-line status rests on noninferiority rather than superiority data. Benefit in extended-window thrombolysis and large-core thrombectomy is real but heterogeneous, and the optimal blood-pressure target after successful reperfusion remains undefined beyond avoiding intensive lowering. Pediatric recommendations are grounded largely in expert consensus and small studies.

Editor's Note

Class of Recommendation codes are quoted directly from the guideline abstract, Top Take-Home Messages, and the New and Impactful Practice-Changing Recommendations summary in the free-access full text on AHA Journals. Level of Evidence letters were not present in that summary table and are left blank pending confirmation against the full recommendation tables. Content is a synthesis of the guideline text, not verbatim reproduction.

Full text source: AHA Journals (Free Access) - 2026 AIS Guideline full text