Summary and evolution of AIS Guidelines

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]Associate Editor(s)-in-Chief: Hasnain Ali Moryani, MBBS[2]

For detailed guidelines please refer here, AHA/ASA complete guidelines for management of Acute Ischemic Stroke.

Summary Evolution of AHA/ASA Stroke Guidelines: 2018, 2019, 2021, and 2026

Scope of Each Guideline:

2018:Comprehensive guideline for early/acute management of AIS in adults. Replaced 2013 guideline.

2019: Focused update to 2018, incorporating new evidence on wake-up stroke thrombolysis, DAPT for minor stroke, and EVT extended windows.

2021: Comprehensive guideline for secondary stroke prevention. Replaced 2014 guideline. Covers risk factor management, antithrombotics, etiology-specific treatment.

2026: New comprehensive guideline for early/acute management of AIS. Replaces 2018/2019. Includes pediatric stroke for the first time.

PART 1: ACUTE MANAGEMENT — EVOLUTION FROM 2018 → 2019 → 2026

IV Thrombolysis

Topic	2018	2019 Update	2026
Thrombolytic agent	Alteplase 0.9 mg/kg (max 90 mg) was the only recommended agent (Class I). Tenecteplase 0.4 mg/kg was Class IIb, investigational only.	No change from 2018.	Tenecteplase 0.25 mg/kg (max 25 mg) OR alteplase 0.9 mg/kg — both Class I. Tenecteplase 0.4 mg/kg is now Class III (Harm).
Standard time window (0–3 h)	Alteplase within 3 h of onset (Class I, LOE A).	No change.	Alteplase or tenecteplase within 4.5 h (Class I). Single unified window.
Extended window (3–4.5 h)	Alteplase within 3–4.5 h (Class I, LOE B-R) with additional exclusion criteria (age >80, OAC use, NIHSS >25, prior stroke + DM).	No change.	Merged into single 0–4.5 h window. Exclusion criteria updated in full guideline text.
Wake-up stroke / unknown onset	Not specifically addressed in 2018 original.	NEW: Alteplase within 4.5 h of recognition if DWI-positive/FLAIR-negative on MRI (Class IIa, LOE B-R).	Extended to 4.5–9 h from last known well or midpoint of sleep with perfusion imaging showing salvageable penumbra (Class IIa).
CMBs and IVT	1–10 CMBs: Class IIa to proceed. >10 CMBs: Class IIb, uncertain benefit.	No change.	Carried forward (consult full guideline).
Pediatric IVT	Not addressed.	Not addressed.	NEW: Alteplase within 4.5 h in patients aged 28 days–18 years (Class IIb).
Door-to-needle time	Goal <60 min from ED arrival (Class I).	No change.	Reaffirmed: initiate as quickly as possible, avoid delays for multimodal imaging (Class I).

Endovascular Thrombectomy

Topic	2018	2019 Update	2026
Standard window (0–6 h) — ASPECTS threshold	ICA/M1 occlusion, NIHSS ≥6, prestroke mRS 0–1, ASPECTS ≥6 (Class I, LOE A).	No change.	ASPECTS 3–10 (Class I). Major expansion to include large-core infarcts.
Extended window (6–24 h) — standard core	DAWN or DEFUSE 3 criteria: small core, large mismatch (Class I within 6–16 h; Class IIa within 16–24 h).	No change.	ASPECTS 3–5 within 6–24 h, age <80, NIHSS ≥6, no mass effect (Class I). Broader eligibility.
Large core (ASPECTS 0–2)	Not addressed.	Not addressed.	NEW: ASPECTS 0–2 within 6 h, age <80, no mass effect (Class IIa).
Prestroke mRS 2	Not addressed (only mRS 0–1 studied).	Not addressed.	NEW: mRS 2 with ASPECTS ≥6 within 6 h (Class IIa).
Posterior circulation (basilar)	Class IIb, limited evidence, uncertain benefit.	No change.	NEW: Basilar occlusion, mRS 0–1, NIHSS ≥10, PC-ASPECTS ≥6, within 24 h (Class I). Major upgrade.
M2/M3 occlusions	Class IIb, uncertain benefit.	No change.	Carried forward (consult full guideline).
Pediatric EVT (≥6 years)	Not addressed.	Not addressed.	NEW: Within 6 h (Class IIa); 6–24 h with salvageable tissue (Class IIa).
Pediatric EVT (28 days–6 years)	Not addressed.	Not addressed.	NEW: Within 24 h with salvageable tissue (Class IIb).
Stent retrievers	Preferred over coil retrievers (Class I).	No change.	Stent retriever or direct aspiration (Class I).
Tirofiban before EVT	Not addressed.	Not addressed.	NEW: Not useful (Class III, No Benefit).
Reperfusion goal	mTICI 2b/3 (Class I).	No change.	Reaffirmed (mTICI 2b, 2c, or 3).

Blood Pressure Management

Topic	2018	2019 Update	2026
Pre-IVT	Lower to <185/110 mm Hg before IVT (Class I).	No change.	Carried forward.
Post-IVT	Maintain <180/105 mm Hg for 24 h (Class I).	No change.	Intensive target <140 mm Hg is Class III (No Benefit). Standard <180/105 remains.
Post-EVT (successful recanalization)	Maintain ≤180/105 mm Hg (Class IIa).	No change.	Intensive target <140 mm Hg for 72 h is Class III (Harm).
No reperfusion therapy	Treat only if SBP >220 or DBP >120 (Class I). Lower by 15% in first 24 h (Class I).	No change.	Carried forward.
Prehospital BP reduction	Not addressed.	Not addressed.	NEW: Early reduction to 130–140 mm Hg is Class III (No Benefit / Harm).

Blood Glucose Management

Topic	2018	2019 Update	2026
Hyperglycemia target	Target 140–180 mg/dL reasonable (Class IIa). Treat hypoglycemia <60 mg/dL (Class I).	No change.	IV insulin targeting 80–130 mg/dL is Class III (No Benefit). Prior 140–180 range remains reasonable.

Antiplatelet Treatment (Acute Phase)

Topic	2018	2019 Update	2026
Aspirin	Aspirin within 24–48 h (Class I, LOE A). Delay 24 h after IVT.	No change.	Carried forward.
DAPT for minor stroke	Not in original 2018.	NEW: DAPT (ASA + clopidogrel) within 24 h for minor stroke (NIHSS ≤3) or high-risk TIA, for 21 days (Class I, LOE A).	DAPT threshold expanded to NIHSS ≤5 (Class IIa). Duration 21–90 days.

Anticoagulants (Acute Phase)

Topic	2018	2019 Update	2026
Urgent anticoagulation	Not recommended for preventing early recurrence (Class III, Harm).	No change.	Carried forward.
Early OAC in AF	Not specifically addressed.	Not specifically addressed.	NEW: Early OAC in milder AIS with AF is reasonable (Class IIa). Efficacy for early recurrence prevention not established.

Stroke Systems of Care / Prehospital

Topic	2018	2019 Update	2026
Mobile stroke units	Not specifically recommended.	Not addressed.	NEW: MSUs recommended where available (Class I).
EMS destination — bypass to distant TSC	Transport to closest capable center (Class I).	No change.	NEW: Bypass to distant TSC (45–60 min) does not improve outcomes when local center available (Class III, No Benefit).
DIDO protocols	Not specifically addressed.	Not addressed.	NEW: Hospitals and EMS should establish transfer protocols to reduce DIDO times (Class I).
Neurointerventionalist credentialing	Not addressed.	Not addressed.	NEW: TSC/CSC hospitals should credential operators using established standards (Class I).
EVT quality tracking	Not addressed.	Not addressed.	NEW: Comprehensive tracking of time metrics and outcomes (Class I).
Prehospital RIC	Not addressed.	Not addressed.	NEW: Class III (No Benefit).
Prehospital GTN	Not addressed.	Not addressed.	NEW: Class III (No Benefit / Harm).
Pediatric prehospital stroke tools	Not addressed.	Not addressed.	NEW: Adult tools perform poorly; pediatric tools uncertain (Class IIb).
Pediatric imaging	Not addressed.	Not addressed.	NEW: MRI/MRA preferred (Class IIa); CT/CTA if MRI unavailable within 25 min (Class IIa).

In-Hospital Management & Complications

Topic	2018	2019 Update	2026
Dysphagia — PES	Not addressed.	Not addressed.	NEW: Pharyngeal electrical stimulation can be beneficial (Class IIa).
Glibenclamide for brain swelling	Not addressed.	Not addressed.	NEW: Not effective (Class III, No Benefit).
Decompressive craniectomy	Effective for malignant MCA edema (Class I). Effective for cerebellar infarction (Class I).	No change.	Carried forward.
DVT prophylaxis	Subcutaneous anticoagulants (Class I). IPCs if anticoagulants contraindicated (Class IIa).	No change.	Carried forward.
Swallowing assessment	Before oral intake (Class I).	No change.	Carried forward.

PART 2: SECONDARY PREVENTION — 2021 GUIDELINE (NEW STANDALONE)

The 2021 guideline (Kleindorfer et al.) was the first comprehensive secondary prevention guideline since 2014. It introduced etiology-based organization and numerous new recommendations. Key highlights are summarized below.

Risk Factor Management

Topic	2014 (Prior Guideline)	2021 Update
Blood pressure target	<140/90 mm Hg (Class I).	<130/80 mm Hg for most patients (Class I, LOE B-R). More aggressive target.
Lipid therapy — atherosclerotic stroke	High-intensity statin (Class I).	High-intensity statin + ezetimibe if needed to LDL-C <70 mg/dL (Class I, LOE A). Added ezetimibe target.
Lipid therapy — no known CHD	Statin recommended.	Atorvastatin 80 mg if LDL-C >100 mg/dL (Class I, LOE A). Specific agent/dose.
Hypertriglyceridemia	Not specifically addressed for stroke.	NEW: Icosapent ethyl 2 g BID if TG 135–499, LDL 41–100, on statin (Class IIa).
Diabetes — glucose-lowering agents	General glycemic control recommended.	NEW: Use agents with proven CV benefit (Class I, LOE B-R). HbA1c ≤7% for most (Class I).
Pioglitazone	Not specifically addressed.	NEW: May be considered ≤6 months post-stroke with insulin resistance, HbA1c <7%, no HF/bladder cancer (Class IIb).
Diet	General healthy diet.	NEW: Mediterranean-type diet recommended (Class IIa). Sodium reduction by ≥1 g/d (Class IIa).
Physical activity	General recommendation.	NEW: Specific targets — moderate 10 min × 4/wk or vigorous 20 min × 2/wk (Class I). Break sedentary time every 30 min (Class IIb).
Obesity	Weight loss recommended.	Referral to intensive multicomponent behavioral program (Class I). Annual BMI calculation (Class I).
OSA	Not specifically addressed.	NEW: CPAP can be beneficial (Class IIa). Evaluation for OSA may be considered (Class IIb).

Antithrombotic Therapy (Secondary Prevention)

Topic	2014	2021 Update
Noncardioembolic stroke — SAPT	Aspirin, clopidogrel, or ASA/dipyridamole (Class I).	No change (Class I, LOE A).
Minor stroke / high-risk TIA — DAPT	Limited recommendation.	NEW: DAPT (ASA + clopidogrel) within 12–24 h, for 21–90 days, then SAPT (Class I, LOE A). NIHSS ≤3, ABCD2 ≥4.
Ticagrelor + ASA	Not addressed.	NEW: For NIHSS ≤5, ABCD2 ≥6, or ≥30% stenosis, for 30 days (Class IIb). Increased bleeding risk noted.
DAPT >90 days	Not recommended.	Class III (Harm) — excess hemorrhage risk (LOE A).
AF — anticoagulation	Warfarin or DOACs (Class I).	DOACs preferred over warfarin in nonvalvular AF (Class I, LOE B-R). Paroxysmal = persistent = permanent (Class I).
AF — timing of OAC after stroke	Not well defined.	High hemorrhagic risk: delay >14 days (Class IIa). Low risk: 2–14 days (Class IIb). TIA: immediate (Class IIa).
AF — LAA closure	Not addressed for secondary prevention.	NEW: Watchman device if contraindication to lifelong OAC but can tolerate ≥45 days (Class IIb).
ESUS	Not defined as category.	NEW: DOACs not recommended (Class III). Ticagrelor not recommended (Class III).

Etiology-Specific Management (New in 2021)

Etiology	Key 2021 Recommendations
Intracranial atherosclerosis (50–99%)	ASA 325 mg/d preferred over warfarin (Class I). DAPT (ASA + clopidogrel) for 90 days if 70–99% stenosis within 30 days (Class IIa). Angioplasty/stenting NOT as initial treatment (Class III, Harm). EC-IC bypass not recommended (Class III).
Extracranial carotid stenosis	CEA for 70–99% stenosis if periop risk <6% (Class I). CEA for 50–69% based on patient factors (Class I). CEA preferred over CAS in age ≥70 or within 1 week (Class IIa). Revascularize within 2 weeks (Class IIa). No revascularization if <50% (Class III).
PFO	NEW: Closure reasonable in ages 18–60 with nonlacunar stroke, undetermined cause, high-risk PFO features (Class IIa). Shared decision-making required (Class I).
Dissection	Antithrombotic therapy ≥3 months (Class I). ASA or warfarin both reasonable <3 months (Class IIa).
Antiphospholipid syndrome	Warfarin with INR 2–3 (Class IIa). Rivaroxaban NOT recommended in triple-positive APS (Class III, Harm).
Sickle cell disease	Chronic transfusion to HbS <30% (Class I). Hydroxyurea if transfusion unavailable (Class IIa).
Valvular disease	Mechanical valve: warfarin (Class I). Dabigatran with mechanical valve: Class III (Harm).
LV thrombus	Warfarin ≥3 months (Class I). DOAC safety uncertain (Class IIb).
Cardiomyopathy (sinus rhythm, reduced EF)	Anticoagulation vs antiplatelet uncertain; individualize (Class IIb). Dabigatran with LVAD: Class III (Harm).
Moyamoya	Surgical revascularization (Class IIa). ASA monotherapy (Class IIb).
Carotid web	Antiplatelet therapy (Class I). Stenting/CEA if refractory (Class IIb).
FMD	Antiplatelet + BP control + lifestyle (Class I).

Diagnostic Workup (New Section in 2021)

Topic	2021 Recommendation
Brain imaging	CT or MRI to confirm diagnosis (Class I).
ECG	Screen for AF/flutter (Class I).
Timing	Diagnostic evaluation completed or underway within 48 h (Class I).
Carotid imaging	Noninvasive imaging for anterior circulation stroke candidates for revascularization (Class I).
Blood tests	CBC, PT, PTT, glucose, HbA1c, creatinine, lipid profile (Class I).
Cryptogenic stroke — echo	TTE with or without contrast (Class IIa).
Cryptogenic stroke — rhythm monitoring	Long-term monitoring with ILR or MCOT (Class IIa).
Hypercoagulable workup	As clinically indicated in cryptogenic stroke (Class IIa).

Health Systems & Behavior Change (New in 2021)

Topic	2021 Recommendation
Quality programs	Hospital-based or outpatient quality monitoring recommended (Class I).
Multidisciplinary teams	Team-based approach for BP, lipids, risk factors (Class IIa).
Behavior change	Interventions targeting stroke literacy, lifestyle, medication adherence (Class I). Information alone is insufficient (Class III, No Benefit).
Health equity	Address social determinants of health (Class I). Monitor performance measures for disparities (Class I). Adopt health literacy toolkit (Class I).

PART 3: CROSS-GUIDELINE SUMMARY — SCOPE AND RELATIONSHIP

	2018	2019	2021	2026
Full Citation	Powers et al., Stroke 2018	Powers et al., Stroke 2019	Kleindorfer et al., Stroke 2021	Prabhakaran et al., Stroke 2026
PMID	29367334	31662037	34024117	41582814
Scope	Acute AIS management (adults)	Focused update to 2018	Secondary stroke prevention	Acute AIS management (adults + pediatric)
Replaces	2013 AIS guideline	Sections of 2018	2014 secondary prevention guideline	2018 and 2019 AIS guidelines
Current Status (2026)	Superseded by 2026	Superseded by 2026	Still active — no replacement published	Current active guideline
Key Innovations	EVT with stent retrievers (Class I); EVT 6–16 h DAWN/DEFUSE 3; comprehensive acute management	Wake-up stroke IVT (DWI-FLAIR mismatch); DAPT for minor stroke (NIHSS ≤3); tenecteplase 0.4 mg/kg (Class IIb)	Etiology-based organization; PFO closure; BP <130/80; LDL <70 with ezetimibe; ESUS recommendations; health equity section	Tenecteplase 0.25 mg/kg (Class I); EVT for large core (ASPECTS 0–5); basilar EVT (Class I); pediatric stroke; MSUs (Class I); multiple Class III (Harm/No Benefit) for intensive BP, glucose, prehospital interventions