Clinical Neurology · Stroke & Vascular Neurology

2026 AHA/ASA Acute Ischemic Stroke

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Source: 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;57:eXXX–eXXX. doi:10.1161/STR.0000000000000513

What’s New vs the 2019 Guideline

Tenecteplase (TNK) is now equivalent to alteplase — both COR 1; 0.25 mg/kg single bolus, max 25 mg.
Non-disabling deficits (e.g., isolated sensory) within 4.5 h: do NOT thrombolyse — DAPT is preferred and recommended (PRISMS, ARAMIS).
EVT expanded to large cores: ASPECTS 3–5 (0–6 h and 6–24 h) is COR 1; ASPECTS 0–2 within 6 h is COR 2a in selected patients <80 y.
Basilar artery occlusion: EVT within 24 h, NIHSS ≥10, PC-ASPECTS ≥6 is COR 1 (ATTENTION, BAOCHE).
First-time pediatric EVT recommendations (≥6 y within 6–24 h, COR 2a; 28 d – 6 y within 24 h, COR 2b).
Tight glucose control (80–130 mg/dL) is NOT recommended — target 140–180 mg/dL (SHINE).
Intensive BP <140 after IVT is NOT recommended; after successful EVT (mTICI 2b/2c/3) it is HARMFUL (ENCHANTED-2).
Adjuvant argatroban / eptifibatide with IVT: not beneficial (MOST); tirofiban pre-EVT: not useful (RESCUE-BT).
Early DOAC for AFib + milder stroke is reasonable (ELAN, OPTIMAS, TIMING) — previously waited 4–14 d.
Pharyngeal Electrical Stimulation (PES) for severe post-stroke dysphagia: COR 2a (new).
IV glibenclamide for malignant edema: not recommended (CHARM trial negative).
Mobile Stroke Units (where available): COR 1.

1. IV Thrombolysis (IVT)

Indications

Disabling deficits suggestive of AIS with onset <4.5 h — COR 1, Level A. Treat as quickly as possible regardless of NIHSS, with safe administration.
Wake-up stroke / unknown onset >4.5 h with DWI-positive / FLAIR-negative MRI mismatch within 4.5 h of symptom recognition — COR 2a, B-R.
4.5–9 h from last known well (or up to 9 h from midpoint of sleep) with salvageable penumbra on automated CTP / MR PWI — COR 2a, B-R (EXTEND, TRACE-3, TIMELESS).
Patients with LVO unable to receive EVT, 4.5–24 h with salvageable penumbra: IVT may be beneficial at expert centers — COR 2b, B-R (TRACE-III).

Choice of thrombolytic — NEW (both equivalent)

Agent	Dose	Class
Tenecteplase (TNK)	0.25 mg/kg IV single bolus, max 25 mg	COR 1, Level A
Alteplase	0.9 mg/kg IV (10% bolus, 90% infusion over 60 min), max 90 mg	COR 1, Level A
Tenecteplase 0.4 mg/kg	Not recommended — no benefit, possible harm (NOR-TEST 2)	COR 3 No Benefit, A

Why TNK is now first-line-eligible

TNK = single ≈5–10 second bolus → simpler workflow, faster DTN and DIDO times, fewer dosing errors. Phase 3 trials (AcT, TRACE-2, ATTEST-2) showed non-inferiority. For LVO bridging, TNK has not been directly compared with alteplase before EVT — pre-specified analysis of ACT showed no difference.

Tenecteplase weight-based dosing (Table 7)

Weight (kg)	TNK dose (mg)	Volume to administer (mL)
<60	15	3
60–<70	17.5	3.5
70–<80	20	4
80–<90	22.5	4.5
≥90	25 (max)	5

Non-disabling deficits (NEW major change)

In eligible adult patients with AIS presenting within 4.5 h with mild, non-disabling deficits (e.g., isolated sensory syndrome), IVT is NOT recommended (COR 3 No Benefit, Level B-R). DAPT is preferred and recommended. Based on PRISMS, ARAMIS, TEMPO-2 — DAPT non-inferior to alteplase with fewer hemorrhagic complications.

Defining “clearly disabling” at presentation (NIHSS 0–5)

Would the deficits, if persistent, prevent basic ADLs (BATHE: bathing/dressing, ambulating, toileting, hygiene, eating) or return to work?

Generally CLEARLY disabling:

Complete hemianopia (NIHSS Vision ≥2)
Severe aphasia (NIHSS Language ≥2)
Hemi-extinction or inattention to >1 modality (NIHSS ≥2)
Any weakness limiting sustained effort against gravity (NIHSS Motor ≥2)

May NOT be clearly disabling:

Isolated mild aphasia (still able to communicate meaningfully)
Isolated facial droop
Mild cortical hand weakness (especially nondominant, NIHSS 0)
Mild hemisensory or hemisensorimotor loss
Mild hemiataxia (can still ambulate)

Pre-treatment BP

SBP <185 AND DBP <110 before IVT — COR 1, B-NR
Use labetalol, nicardipine, or clevidipine; avoid excessive lowering (initial target ≈15% reduction).

Extended-window IVT trial selection criteria (Table 3)

Trial	Window	Imaging mismatch
WAKE-UP, THAWS	Unknown onset / wake-up	DWI-positive / FLAIR-negative
EPITHET	3–6 h	PWI/DWI ratio >1.2, PWI–DWI ≥10 mL (Tmax >2 s)
ECASS-4	>4.5–9 h	PWI/DWI ratio ≥1.2, PWI ≥20 mL
EXTEND	>4.5–9 h	CTP or DWI/PWI mismatch >1.2, penumbra–core >10 mL, core <70 mL
TIMELESS	4.5–24 h	RAPID: mismatch ratio >1.8, penumbra >15 mL, core <70 mL
TRACE-3	4.5–24 h	Same as TIMELESS (iStroke software)

Contraindications (Table 8 — summary)

Absolute contraindications

CT with clear hypodensity attributable to clinical symptoms
CT with acute intracranial hemorrhage
Moderate-to-severe TBI within 14 d (LOC >30 min, GCS <13, hemorrhage/contusion/skull fx)
Neurosurgery (intracranial/spinal) within 14 d
Acute spinal cord injury within 3 months
Intra-axial intracranial neoplasm
Symptoms consistent with infective endocarditis
Severe coagulopathy: platelets <100k, INR >1.7, aPTT >40 s, PT >15 s
Known or suspected aortic arch dissection
ARIA / on amyloid immunotherapy — risk unknown, avoid

Relative contraindications (individualized decision)

Pre-existing disability / frailty
DOAC exposure within 48 h — individualized; consider timing of last dose, renal function, stroke severity, reversal availability, anti-Xa / dTT assays
Ischemic stroke within 3 months
Prior ICH (amyloid angiopathy higher risk than HTN-related)
Recent major non-CNS trauma 14 d–3 months
Recent major non-CNS surgery within 10 d
Recent GI/GU bleeding within 21 d
Intracranial arterial dissection — safety unknown
Untreated intracranial vascular malformation — safety unknown
Recent STEMI within 3 months (consult cards — hemopericardium risk)
Acute pericarditis (reasonable for major AIS with cards consult)
LA/LV thrombus (reasonable for disabling AIS with cards consult)
Systemic active malignancy — onco consult
Pregnancy / post-partum (consider for moderate-severe stroke, OB consult)
Dural puncture within 7 d
Arterial puncture of noncompressible vessel within 7 d
Moderate-severe TBI 14 d–3 months / Neurosurgery 14 d–3 months

Benefit generally > bleeding risk — IVT is reasonable

Extracranial cervical artery dissection (reasonably safe within 4.5 h)
Extra-axial intracranial neoplasm (meningioma)
Post-angiographic procedural stroke
Unruptured intracranial aneurysm — low risk
Stable prior GI/GU bleed (case-by-case)
Remote MI
Recreational drug use
Stroke-mimic uncertainty (IVT-in-mimic ICH risk ≈0.5%)
Moya-Moya disease
Sickle cell disease — IV alteplase safe and effective (COR 2a)
Microbleeds 1–10 on prior MRI — do not delay/screen for CMBs; treat unless >10 known burden

Adjuvant antithrombotics with IVT — all NOT recommended

Intervention	Recommendation	Class
IV argatroban with IVT	Not effective for long-term outcomes (MOST)	COR 3 No Benefit, A
IV eptifibatide with IVT	Not effective (MOST)	COR 3 No Benefit, A
IV abciximab with IVT	Harm — increased sICH (AbESTT-II)	COR 3 Harm, B-R
IV tirofiban with IVT (general)	Uncertain	COR 2b, B-R
IV aspirin within 90 min of alteplase	Harm — increased sICH (ARTIS)	COR 3 Harm, B-R
Sonothrombolysis as adjunct	No benefit	COR 3 No Benefit, A

Post-IVT complications

Symptomatic ICH within 24 h (Table 5)

Stop alteplase infusion (if still being pushed)
Emergent CBC, PT/INR, aPTT, fibrinogen, type & cross
Emergent NCCT head
Cryoprecipitate 10 units IV over 10–30 min (target fibrinogen ≥150 mg/dL)
Tranexamic acid 1000 mg IV over 10 min OR aminocaproic acid 4–5 g over 1 h then 1 g/h × 8 h
Hematology + neurosurgery consult
BP, ICP, glucose, temperature control

Orolingual angioedema (Table 6)

Intubation may not be needed if edema limited to anterior tongue/lips
Larynx/palate/floor-of-mouth/oropharynx involvement OR progression in 30 min → anesthesia, awake fiberoptic or cricothyroidotomy (avoid nasotracheal)
Discontinue thrombolytic if still infusing; hold ACE inhibitors
Methylprednisolone 125 mg IV
Diphenhydramine 50 mg IV
Ranitidine 50 mg IV or famotidine 20 mg IV
If progression: epinephrine SC 0.3 mL (1 mg/mL) or nebulizer
Icatibant 3 mL (30 mg) SC (max 3 doses q6h, bradykinin B2 antagonist) OR C1 esterase inhibitor 20 IU/kg

Practical — do NOT delay IVT to wait for coagulation labs. In patients without known coagulopathy, do not delay IVT waiting for platelet count / coag results. Initiate IVT; stop if abnormal results return. (COR 2a, B-NR)

2. Endovascular Thrombectomy (EVT)

Anterior circulation — algorithm summary

Window	ASPECTS	NIHSS	Prestroke mRS	Class
0–6 h	3–10	≥6	0–1	COR 1, A
0–6 h	0–2 (very large core)	≥6	0–1	COR 2a, B-R (age <80, no mass effect)
0–6 h	≥6	≥6	2 (mild pre-existing)	COR 2a, B-NR
0–6 h	3–10	≥6	3–4	COR 2b, B-NR
6–24 h	6–10	≥6	0–1	COR 1, A
6–24 h (selected)	3–5	≥6	0–1	COR 1, A (age <80, no mass effect)
0–6 h dominant M2	≥6	≥6	0–1	COR 2a, B-NR
Non-dom M2, distal MCA, ACA, PCA	—	—	—	COR 3 No Benefit, A (ESCAPE-MeVO, DISTAL)

Posterior circulation — basilar artery occlusion (NEW)

Population	Recommendation	Class
Basilar occlusion, NIHSS ≥10, PC-ASPECTS ≥6, mRS 0–1, within 24 h	EVT recommended — better outcomes and mortality (ATTENTION, BAOCHE)	COR 1, A
Basilar occlusion, NIHSS 6–9, PC-ASPECTS ≥6, within 24 h	Effectiveness not well established	COR 2b, B-R

EVT in pediatric patients (NEW)

Age	Time window	Imaging requirement	Class
≥6 y	0–6 h, LVO	—	COR 2a, B-NR
≥6 y	6–24 h, LVO	Salvageable tissue	COR 2a, B-NR
28 d – 6 y	Within 24 h, LVO	Salvageable tissue + experienced neurointerventionalist	COR 2b, B-NR
Neonates <28 d	—	—	Insufficient data

EVT technique

Stent retriever, contact aspiration, or combination — all COR 1, A (ASTER, COMPASS, ASTER-2)
Target reperfusion: mTICI 2b/2c/3 (COR 1, B-R)
General anesthesia or procedural sedation — equivalent in 0–6 h (COR 1, B-R); data insufficient for 6–24 h
Tirofiban pre-EVT: NOT useful (RESCUE-BT) — COR 3 No Benefit
Rescue intracranial balloon angioplasty / stenting after failed EVT: uncertain (COR 2b)
Intra-arterial alteplase/urokinase/TNK after near-complete EVT for completion: may be reasonable (COR 2b — CHOICE, POST-TNK)
Emergent extracranial carotid stenting for tandem occlusions: may be reasonable (COR 2b, B-NR — TITAN, PICASSO)

Bridging IVT before EVT — do NOT skip. If a patient is eligible for both, IVT should be given as rapidly as possible. Do not “skip” IVT to facilitate EVT (COR 1, A). Time-from-onset-to-IVT <2 h 20 min drives the bridging benefit. Do not delay EVT to assess clinical response after IVT.

EVT time goals

Door-to-CT/CTA: ≤25 min
Door-to-needle (IVT): <45 min (goal >50% <30 min)
Door-in-door-out (DIDO) for transfers: track and reduce (COR 1)
EVT-capable hospitals should track door-to-puncture, door-to-reperfusion, mTICI rates (COR 1)

3. Prehospital & EMS Systems

Public stroke awareness programs at all levels — COR 1, B-R/B-NR
EMS dispatcher use of telephone stroke assessment tool — COR 2a, B-NR
EMS stroke screen by paramedics — COR 1, A (CPSS, LAPSS, RACE, LAMS, FAST-PLUS)
EMS hospital prenotification — COR 1, B-NR (shorter DTN, fewer minutes lost)
Mobile Stroke Units where available — COR 1 (improved onset-to-treatment, functional outcomes)
Prehospital remote ischemic conditioning (RIC) — NOT recommended (RESIST) — COR 3 No Benefit
Prehospital transdermal GTN — HARM (MR ASAP, RIGHT-2) — COR 3 Harm
Intensive prehospital BP lowering to 130–140 — no benefit — COR 3 No Benefit

EMS destination

Scenario	Recommendation	Class
Closest appropriate stroke-capable hospital (ASRH / PSC / TSC / CSC)	Recommended over non-stroke hospitals	COR 1, B-NR
Suspected LVO (e.g., RACE >4), within local TSC reach	Direct triage to TSC reasonable	COR 2a, B-NR
No local TSC: consider closest IVT-capable + secondary transfer	May be reasonable if doesn’t disqualify from IVT	COR 2b, B-NR
Well-coordinated SSOC with proficient local PSC: direct transport to distant TSC (45–60 min)	Does NOT improve outcomes — bypass not beneficial	COR 3 No Benefit, B-R
DIDO protocols for inter-hospital transfer	Establish to reduce DIDO times	COR 1, B-NR

4. Imaging

NCCT or MRI to exclude ICH before IVT — COR 1, A
Door-to-imaging ≤20–25 min — COR 1, B-NR
Vascular imaging (CTA/MRA) for suspected LVO — should NOT be delayed for creatinine — COR 1, B-NR
Wake-up / unknown onset >4.5 h: DWI/FLAIR mismatch MRI for extended IVT — COR 2a, B-R
CTP or MR DWI/PWI with automated postprocessing for 6–24 h EVT selection — COR 2a (or 1 if needed)
Advanced imaging not strictly required for 0–6 h EVT once LVO confirmed (NCCT + CTA may suffice)

ASPECTS scoring (10 points)

Anterior MCA (basal ganglia level): caudate, putamen, internal capsule, insular cortex, anterior MCA cortex (M1, frontal operculum), lateral MCA cortex (M2, lateral to insular ribbon / anterior temporal), posterior MCA cortex (M3, posterior temporal) — 1 point each
Anterior MCA (coronal radiata level): anterior-superior (M4), lateral-superior (M5), posterior-superior (M6) — 1 point each
PC-ASPECTS (posterior, 10 points): thalami (1 each), occipital lobes (1 each), midbrain (2), pons (2), cerebellar hemispheres (1 each)

ECG and troponin: recommended at baseline but should NOT delay IVT/EVT (both COR 1).

5. Blood Pressure Management

Phase / Scenario	Target / Recommendation	Class
Hypotension / hypovolemia	Correct to maintain systemic perfusion	COR 1, C-LD
BP ≥220/120, no IVT/EVT, no other indication	Initiating antihypertensives in first 48–72 h uncertain	COR 2b, C-EO
BP <220/120, no IVT/EVT, no other indication	Antihypertensives in first 48–72 h NOT effective	COR 3 No Benefit, A
Before IVT	SBP <185 / DBP <110	COR 1, B-NR
Before EVT (no IVT given)	SBP ≤185 / DBP ≤110 reasonable	COR 2a, B-NR
First 24 h after IVT	BP <180/105	COR 1, B-R
After IVT, mild-mod AIS — intensive SBP <140	NOT recommended — no functional benefit	COR 3 No Benefit, B-R
During / 24 h after EVT (general)	BP ≤180/105 reasonable	COR 2a, B-NR
72 h after successful EVT (mTICI 2b/2c/3), no other indication — intensive SBP <140	HARMFUL — NOT recommended	COR 3 Harm, A

Why aggressive BP lowering after successful EVT is harmful

Two high-quality RCTs (BP-TARGET, ENCHANTED-2 sub-analyses) showed intensive SBP <140 — and especially <120 — after complete reperfusion led to more neurological deterioration and disability at 90 days. The penumbra is gone, but autoregulation is impaired; aggressive lowering causes secondary ischemia. Maintain SBP 140–180 after good reperfusion.

6. Other Acute Care

Glucose (CHANGE from 2019)

Hypoglycemia <60 mg/dL: treat to normoglycemia — COR 1, C-LD
Persistent hyperglycemia: target 140–180 mg/dL — COR 2a, C-LD
Tight glucose control 80–130 mg/dL is NOT recommended — no benefit, increases severe hypoglycemia (SHINE) — COR 3 No Benefit, A

Temperature

Treat hyperthermia >37.5 °C; target normothermia (nurse-driven protocols reduce mortality) — COR 1, B-R
Identify and treat source of fever (e.g., infection) — COR 1, C-EO
Induced hypothermia or prophylactic fever prevention — NOT recommended — COR 3 No Benefit

Oxygenation

Airway / ventilation support as needed — COR 1
Supplemental O₂ to keep SpO₂ >94% in hypoxic patients — COR 1
Routine supplemental O₂ in non-hypoxic AIS — NOT recommended — COR 3 No Benefit
Hyperbaric O₂ only for cerebral air embolism (COR 2b); not for general AIS
Normobaric hyperoxia before EVT (NIHSS 10–20, ASPECTS ≥6, anterior LVO) — may be reasonable (COR 2b, OPENS-2)

Head position, volume expansion, neuroprotection — what NOT to do

Routine 0-degree head positioning × 24 h — NOT beneficial (HeadPoST, HOPES-2) — COR 3 No Benefit
Hemodilution, high-dose albumin, pentoxifylline — NOT recommended — COR 3 No Benefit, A
Counterpulsation / sphenopalatine ganglion stimulation — NOT recommended — COR 3 No Benefit
Pharmacologic / nonpharmacologic neuroprotectants (nerinetide, uric acid, edaravone-dexborneol, ApTOLL) — NOT recommended — COR 3 No Benefit, A
Emergency CEA / stenting for stroke-in-evolution without intracranial clot (within 48 h) — NOT beneficial — COR 3 No Benefit

7. Antiplatelet Therapy — Early Secondary Prevention

Aspirin within 48 h of stroke onset — reduces death and dependency — COR 1, A (IST, CAST)
Postpone aspirin until 24 h after IVT — early aspirin <90 min after alteplase is HARM (ARTIS)

DAPT for minor AIS / high-risk TIA — COR 1, A

Trial	Inclusion	Drug & duration	LKN	NNT
CHANCE	NIHSS ≤3 or TIA ABCD² ≥4	Clopi 300 mg load → 75 mg + ASA 75 mg × 21 d, then clopi	24 h	28
POINT	NIHSS ≤3 or TIA ABCD² ≥4	Clopi 600 mg load → 75 mg + ASA 50–325 mg × 90 d	12 h	67
THALES	NIHSS ≤5 or TIA ABCD² ≥6	Ticagrelor 180 mg load → 90 mg BID + ASA 300–325 mg load → 75–100 mg × 30 d	24 h	91
CHANCE-2	NIHSS ≤3 or TIA ABCD² ≥4 + CYP2C19 LOF allele	Ticagrelor 180 mg load → 90 mg BID + ASA × 21 d, then ticagrelor	24 h	63
INSPIRES	NIHSS ≤5 or TIA ABCD² ≥4, presumed atherosclerosis	Clopi 300 mg load → 75 mg + ASA 100–300 mg load → 100 mg × 21 d	72 h	53

Practical DAPT algorithm (Figure 4 in guideline)

Step through these in order:

If eligible for IVT/EVT → reperfuse first; DAPT decision after
LKN <24 h AND NIHSS ≤3 or ABCD² ≥4: DAPT clopidogrel + ASA × 21 d, then SAPT (COR 1, A — CHANCE/POINT)
If CYP2C19 LOF allele carrier: switch to ticagrelor + ASA × 21–30 d (COR 2b, B-R — CHANCE-2/THALES)
LKN <24 h AND NIHSS 4–5 with ≥50% intracranial/extracranial stenosis: clopi + ASA × 21 d, then SAPT (COR 2a, B-R)
LKN 24–72 h AND NIHSS ≤5 or ABCD² ≥4 with presumed atherosclerosis: clopi + ASA × 21 d (COR 2a, B-R — INSPIRES)
Continuing DAPT beyond 90 days is NOT beneficial and increases bleeding

Antiplatelet — what NOT to do

Intervention	Recommendation	Class
Triple antiplatelet (ASA + clopi + dipyridamole)	Harm — TARDIS	COR 3 Harm, B-R
Routine antiplatelet added to anticoagulation in AFib without CAD/recent stent	Harm — increased bleeding	COR 3 Harm, B-NR
IV abciximab with IVT	Harm	COR 3 Harm, B-R
Ticagrelor monotherapy over aspirin (SOCRATES)	No benefit	COR 3 No Benefit, B-R
Continuing DAPT >90 d	No benefit, increased bleeding	COR 3 No Benefit

8. Anticoagulation

AFib — early DOAC initiation (NEW)

Carefully selected (milder severity) AIS + AFib: early DOAC initiation poststroke is low risk and reasonable (COR 2a, A — ELAN, OPTIMAS, TIMING)
ELAN definitions: “early” = within 48 h for minor/moderate stroke, day 6/7 for major; “late” = day 3/4 minor, day 12–14 major
OPTIMAS: early DOAC (≤4 d) non-inferior to delayed (7–14 d); fewer recurrent events with early

Anticoagulation — what NOT to do

Intervention	Recommendation	Class
IV argatroban with IVT	Not effective for long-term outcomes (MOST)	COR 3 No Benefit, A
Early anticoagulation (<48 h) of undifferentiated AIS	Does NOT reduce neuro worsening or improve outcome	COR 3 No Benefit, A

Argatroban for early neuro deterioration — emerging evidence

The 2022 ARAIS trial of argatroban + IVT was neutral overall. A 2024 single-arm Chinese trial in patients with early neuro deterioration (NIHSS worsening ≥2 within 48 h) suggested benefit, but this was open-label and Han Chinese only. Routine argatroban + IVT remains NOT recommended; use for END is still investigational.

9. In-Hospital Management — General Supportive Care

Stroke unit care

Treatment within an organized inpatient stroke unit by a specialty-trained interdisciplinary team is recommended for all AIS patients (COR 1, B-R). Benefits independent of age, sex, severity, stroke type, or follow-up duration; most evident in geographically colocalized units.

Dysphagia (PES is NEW)

Bedside swallow screen before any PO intake — COR 1, C-EO
Dysphagia evaluation by SLP or trained professional — COR 2a, C-LD
Endoscopic swallow exam (FEES) for patients failing/unable to participate — COR 2a, B-NR
Oral hygiene protocol may reduce pneumonia — COR 2b, B-NR
Pharyngeal Electrical Stimulation (PES) for severe stroke with dysphagia — COR 2a, B-R (NEW) — 3 consecutive once-daily treatments via NG tube
PES in severe stroke requiring tracheostomy / mechanical ventilation — COR 2a, B-R (NEW) — expedites decannulation

Nutrition

Enteral diet started within 7 d — COR 1, B-R
Nutritional screening within 48 h — COR 1, B-NR (MNA, CONUT, GNRI, MUST)
NG tube initially × 7 d; PEG if persistent dysphagia >2–3 weeks — COR 2a, B-NR
Early PEG within 7 d is NOT beneficial vs NG (FOOD-3)

DVT prophylaxis

Intervention	Recommendation	Class
Intermittent pneumatic compression (IPC) in addition to routine care	Recommended over routine care alone (CLOTS-3)	COR 1, B-R
Prophylactic-dose SC heparin (UFH or LMWH)	Reasonable to reduce VTE risk	COR 2a, B-R
LMWH vs UFH preference	Slight DVT advantage to LMWH, possibly more bleeding	COR 2b, A
Elastic compression stockings	HARM — skin breakdown, ulceration, necrosis (CLOTS-1/2)	COR 3 Harm, B-R

Depression

Routine post-stroke depression screening — COR 1, B-NR (PHQ-9 or HDS)
Treatment with antidepressants and/or non-pharm (psychotherapy, NIBS, acupuncture) — COR 1, B-R
Prophylactic SSRIs for motor recovery in non-depressed patients — NOT effective (FOCUS, AFFINITY, EFFECTS) — COR 3 No Benefit, A

Other in-hospital

Palliative care referral for select severe stroke patients — COR 2a, C-EO
Routine prophylactic antibiotics — NOT beneficial (PASS, STROKE-INF, PRECIOUS) — COR 3 No Benefit, A
Routine indwelling bladder catheters — HARM (CAUTI risk) — COR 3 Harm, C-LD

Rehabilitation

In-hospital interdisciplinary rehab assessment at appropriate level — COR 1, A
Prophylactic SSRIs for motor recovery — NOT effective — COR 3 No Benefit
Very early high-dose mobilization <24 h: HARM (AVERT) — COR 3 Harm, B-R

10. Acute Complications

Brain swelling — general

Early shared decision-making with family for large infarcts at risk of malignant edema — COR 1, C-EO
Close neurological monitoring in the first days — COR 1, C-EO
Early transfer to facility with neurosurgery and critical-care expertise — COR 1, C-LD

Brain swelling — medical management

Intervention	Recommendation	Class
Osmotic therapy (mannitol or hypertonic saline) as bridge to surgery	Reasonable to improve outcome and mortality	COR 2a, C-LD
IV glibenclamide for large hemispheric infarct 18–70 y	NOT recommended — CHARM trial neutral	COR 3 No Benefit, B-R
Hypothermia, barbiturates, corticosteroids	HARM — lack of efficacy + adverse effects	COR 3 Harm, C-LD

Decompressive surgery — supratentorial

Population	Recommendation	Class
≤60 y, unilateral MCA infarct, neuro deterioration within 48 h despite medical therapy	Decompressive hemicraniectomy with dural expansion — beneficial (DECIMAL, DESTINY, HAMLET)	COR 1, A
>60 y, unilateral MCA infarct, deteriorating within 48 h	May be considered to reduce mortality (worse functional outcomes — DESTINY-II)	COR 2b, B-R
Decreased LOC attributed to swelling	Reasonable trigger for decompressive selection	COR 2a, B-NR
Post-IVT with malignant edema	Early decompression within 48 h may still be considered without added safety concerns	COR 2b, B-NR

Cerebellar infarction — surgical

Cerebellar infarction with obstructive hydrocephalus → ventriculostomy recommended (COR 1, C-LD)
Cerebellar infarction with brainstem compression OR volume ≥35 mL → decompressive suboccipital craniectomy with dural expansion (COR 1, B-NR)

Seizures

Unprovoked post-stroke seizure: AED therapy based on patient-specific factors — COR 1, C-LD
Prophylactic AEDs in AIS: NOT recommended — COR 3 No Benefit, C-LD

Quick-Reference Summary Tables

IVT — comparison of windows

	Onset <4.5 h	Wake-up / 4.5–9 h with mismatch	4.5–24 h LVO not eligible for EVT
Class	COR 1, A	COR 2a, B-R	COR 2b, B-R
Imaging needed	NCCT (CTA if LVO suspected)	DWI/FLAIR mismatch OR CTP/PWI (TIMELESS / EXTEND profile)	Penumbra on CTP / MR DWI-PWI
Agent	TNK 0.25 mg/kg max 25 mg OR alteplase 0.9 mg/kg max 90 mg	Same	Same
Non-disabling deficits	NOT recommended — use DAPT	—	—

EVT — quick reference (anterior LVO)

Window	ASPECTS 6–10	ASPECTS 3–5	ASPECTS 0–2
0–6 h, mRS 0–1	COR 1	COR 1	COR 2a (age <80)
6–24 h, mRS 0–1	COR 1	COR 1 (age <80, no mass effect)	Insufficient data
Posterior basilar 0–24 h	PC-ASPECTS ≥6, NIHSS ≥10 → COR 1	NIHSS 6–9 → COR 2b	—

BP targets at a glance

Phase	Target
Before IVT	<185/110
Before EVT (no IVT)	≤185/110
First 24 h after IVT	<180/105 (NOT <140)
During / 24 h after EVT	≤180/105 (NOT <140)
72 h after successful EVT (mTICI 2b/2c/3)	140–180 — intensive <140 is HARMFUL
Not eligible for reperfusion, BP <220/120	No active lowering for 48–72 h unless other indication

High-Yield “Don’t Do This” — 2026 COR 3 List

IVT in non-disabling deficits within 4.5 h (use DAPT instead)
Tenecteplase at 0.4 mg/kg
IV abciximab with IVT (Harm)
Early IV aspirin within 90 min of alteplase (Harm)
Tirofiban pre-EVT
EVT for non-dominant M2, distal MCA, ACA, PCA (No Benefit)
Tight glucose control 80–130 mg/dL
Intensive BP <140 after IVT in mild-mod AIS
Intensive BP <140 for 72 h after successful EVT (HARM)
Routine supplemental O₂ in non-hypoxic AIS
Routine HBO in AIS (only for air embolism)
0-degree head positioning routinely × 24 h
Hemodilution, high-dose albumin, pentoxifylline
Pharmacologic / nonpharmacologic neuroprotectants
Emergency CEA/stenting for stroke-in-evolution without intracranial clot
Triple antiplatelet therapy (Harm)
Anticoagulant + antiplatelet for AFib without CAD/recent stent (Harm)
Ticagrelor monotherapy over aspirin
DAPT continued beyond 90 days
Argatroban with IVT
Early anticoagulation (<48 h) of undifferentiated AIS
Elastic compression stockings (Harm)
Routine prophylactic antibiotics
Routine indwelling bladder catheters (Harm)
SSRIs for motor recovery in non-depressed
Very early high-dose mobilization <24 h (Harm)
IV glibenclamide for malignant edema
Hypothermia / barbiturates / corticosteroids for AIS swelling (Harm)
Prophylactic AEDs in AIS
Prehospital transdermal GTN (Harm)
Prehospital remote ischemic conditioning (RIC)
Intensive prehospital BP lowering to 130–140
Direct transport to distant TSC bypassing proficient local PSC in well-coordinated SSOC
Sonothrombolysis as adjunct to IVT
IV streptokinase (Harm)

Key Trials by Topic

Topic	Trials
Early IVT (0–4.5 h)	NINDS, ECASS-III
Wake-up / unknown onset IVT	WAKE-UP, THAWS
Extended-window IVT with perfusion	EPITHET, ECASS-4, EXTEND, TIMELESS, TRACE-3
Tenecteplase non-inferiority	AcT, TRACE-2, ATTEST-2, NOR-TEST
Early-window EVT	HERMES (MR CLEAN, ESCAPE, REVASCAT, SWIFT-PRIME, EXTEND-IA)
6–24 h EVT with mismatch	DAWN, DEFUSE-3
Large-core EVT (ASPECTS 3–5)	SELECT-2, RESCUE-Japan LIMIT, ANGEL-ASPECT, TENSION, TESLA
Very large core (ASPECTS 0–2)	LASTE
Basilar artery EVT	ATTENTION, BAOCHE
Medium/distal vessel EVT (neutral)	ESCAPE-MeVO, DISTAL
DAPT for minor stroke / high-risk TIA	CHANCE, POINT, THALES, CHANCE-2, INSPIRES
Early DOAC for AFib stroke	ELAN, OPTIMAS, TIMING
Tight glucose (negative)	SHINE
Intensive BP post-EVT (harmful)	BP-TARGET, ENCHANTED-2
Head position (neutral)	HeadPoST, HOPES-2
Argatroban / eptifibatide adjuncts (neutral)	MOST, ARAIS
Prehospital RIC (neutral)	RESIST
Prehospital GTN (harmful)	MR ASAP, RIGHT-2
Glibenclamide for malignant edema (neutral)	CHARM
DVT prophylaxis	CLOTS-1, CLOTS-2 (stockings harm), CLOTS-3 (IPC benefit)
Decompressive hemicraniectomy	DECIMAL, DESTINY, HAMLET, DESTINY-II
Very early mobilization (harmful)	AVERT
SSRIs for motor recovery (neutral)	FOCUS, AFFINITY, EFFECTS

Compiled by Ahmed Koriesh, MD · summarized from the 2026 AHA/ASA guideline.