Stroke Evidence Map

IV alteplase/TNK within 3 hours

IV alteplase (0.9 mg/kg) or TNK (0.25 mg/kg single bolus) is recommended for eligible patients within 3 hours of symptom onset.

AHA/ASA 2026, §4.6.1

IV alteplase/TNK 3–4.5 hours

IV alteplase/TNK is recommended for eligible patients 3–4.5 hours from onset, with additional exclusion criteria (age >80 per ECASS III).

AHA/ASA 2026, §4.6.2

TNK is the recommended thrombolytic

Tenecteplase (0.25 mg/kg single IV bolus, max 25 mg) is the preferred thrombolytic. Pooled analysis of five RCTs (AcT, ORIGINAL, ATTEST-2, TASTE, BRIDGE-TNK) shows superiority over alteplase for excellent outcomes (OR 1.14 for mRS 0-1, 95% CI 1.03-1.25). Logistic advantages: single bolus vs. 1-hour infusion.

AHA/ASA 2026, §4.6.1 (AcT, ORIGINAL, ATTEST-2, TASTE, BRIDGE-TNK)

IVT reasonable for mild but disabling deficits

IVT is reasonable for patients with mild but functionally disabling deficits (e.g., isolated aphasia, dominant-hand paresis in a surgeon, monocular blindness in a commercial driver). Per AHA/ASA 2026 Table 4: deficit severity is determined by functional impact, not NIHSS score alone. Do not withhold IVT solely because NIHSS is low.

AHA/ASA 2026, §4.6.1, Table 4

IVT not recommended for non-disabling deficits

IVT is not recommended for patients with non-disabling deficits (e.g., isolated facial droop, mild non-dominant hand weakness, hemisensory loss). DAPT may be preferred. See Table 4 for deficit classification.

AHA/ASA 2026, §4.6.1, Table 4

Intervention: IV tPA (alteplase) 0.9 mg/kg

Landmark trial establishing IV tPA within 3 hours of stroke onset.

Intervention: IV tPA (alteplase) 0.9 mg/kg in 3–4.5h window

Extended IV tPA window to 4.5 hours with additional exclusion criteria.

IV tPA/TNK 4.5–9h with perfusion mismatch

IV thrombolysis can be beneficial for selected patients 4.5–9h from known onset when perfusion imaging shows salvageable tissue. Wake-up strokes with unknown onset use ivt-perfusion-wakeup instead. EXTEND provides the strongest positive alteplase signal; ECASS-4 used broader MRI mismatch criteria and was neutral after early stopping, so the pathway should be framed as mismatch-selected benefit rather than guaranteed late-window efficacy.

AHA/ASA 2026, §4.6.3 (EXTEND, ECASS-4)

IVT for wake-up stroke with CTP perfusion mismatch

IV thrombolysis can be beneficial for wake-up stroke patients with unknown onset when CTP perfusion imaging shows mismatch and ischemic core < 70 mL. This parallels the ivt-wakeup-mri (DWI-FLAIR) pathway but uses CT perfusion instead of MRI for onset estimation.

AHA/ASA 2026, §4.6.3 (EXTEND)

IVT for wake-up stroke with DWI-FLAIR mismatch

IV alteplase can be beneficial for wake-up stroke patients with DWI-FLAIR mismatch on MRI, suggesting onset within 4.5h. (WAKE-UP trial: 53.3% vs 41.8% mRS 0-1)

AHA/ASA 2026, §4.6.3 (WAKE-UP)

IVT for non-LVO 4.5–24h with perfusion mismatch

TNK (0.25 mg/kg) may be reasonable for non-LVO patients 4.5–24h with perfusion mismatch. OPTION: 43.6% vs 34.2% mRS 0-1. Not all extended-window reperfusion trials show clinical benefit: CHABLIS-T II (n=224, LVO) achieved radiographic reperfusion at 4.5–24h but 90-day outcomes did not improve when 55% went to preplanned EVT — patient selection and EVT access determine the benefit.

AHA/ASA 2026, §4.6.4 (OPTION)

IVT for LVO 4.5–24h without EVT access, perfusion-selected

TNK (0.25 mg/kg) may be reasonable for LVO patients 4.5–24h when EVT is not available, selected by perfusion mismatch (core <70 mL, ratio ≥1.8). TRACE-III: 33.0% vs 24.2% mRS 0-1 (NNT 11), sICH 3.0% vs 0.8%. If EVT is available and feasible, prioritize EVT (Class I). This recommendation addresses community hospitals and settings where EVT access is delayed or unavailable.

AHA/ASA 2026, §4.6.4 (TRACE-III)

Intervention: IV tPA (alteplase) 4.5–9h with perfusion mismatch

IV tPA in extended window (4.5–9h or wake-up) selected by perfusion imaging mismatch.

Intervention: IV tPA (alteplase) guided by DWI-FLAIR mismatch in unknown-onset stroke

MRI-guided thrombolysis for stroke with unknown time of onset. DWI-FLAIR mismatch selects patients likely within 4.5h.

Intervention: IV alteplase 0.9 mg/kg in 4.5–24h with perfusion-defined salvageable tissue and no initial EVT plan

Alteplase in the 4.5–24h window for perfusion-selected patients who were not initially planned for thrombectomy. Positive — improved 90-day functional independence despite more sICH.

Intervention: IV Tenecteplase (TNK) 0.25 mg/kg in 4.5–24h for non-LVO with perfusion mismatch

TNK in the extended window for non-LVO stroke with salvageable tissue on perfusion imaging. Positive — improved excellent 90-day outcome, with more sICH.

Intervention: IV Tenecteplase (TNK) 0.25 mg/kg in 4.5–24h for LVO patients without EVT access, selected by perfusion mismatch

TNK in extended window (4.5–24h) for LVO patients without EVT access, selected by perfusion mismatch.

Intervention: IV Tenecteplase (TNK) 0.25 mg/kg vs alteplase within 4.5h

Largest TNK non-inferiority trial (n=1465). TNK non-inferior to alteplase for mRS 0-1 at 90 days in Chinese stroke patients within 4.5h.

Intervention: IV Tenecteplase (TNK) 0.25 mg/kg vs alteplase, CTP-selected, non-EVT candidates

Non-inferiority trial of TNK vs alteplase in CTP-selected patients within 4.5h who were not EVT candidates. Non-inferior per-protocol; ITT did not meet NI margin.

Intervention: IV Tenecteplase (TNK) 0.25 mg/kg before EVT vs EVT alone for LVO

Bridge therapy trial: TNK before EVT vs EVT alone in LVO patients within 4.5h. TNK+EVT superior for functional independence (52.9% vs 44.1% mRS 0-2). Definitively answers "should I give IVT before EVT?" — Yes.

Intervention: IV Tenecteplase (TNK) 0.25 mg/kg vs alteplase

Non-inferiority trial of TNK vs alteplase. TNK was non-inferior, simpler to administer (single bolus).

EVT within 6 hours for anterior LVO

Mechanical thrombectomy is recommended for patients with anterior LVO (ICA, M1) within 6 hours of onset, NIHSS ≥6, ASPECTS ≥6, pre-mRS 0-1. Do NOT skip IVT to facilitate EVT; do NOT delay EVT to observe IVT response. For NIHSS <6 with LVO and functionally disabling deficit, see COR IIb mild-disabling pathway.

AHA/ASA 2026, §4.7.2

Intervention: Intra-arterial treatment (EVT) within 6h

First positive EVT trial. Proved benefit of endovascular treatment for anterior LVO.

Intervention: EVT within 12h with favorable imaging

EVT with emphasis on fast workflow and favorable collaterals on multiphase CTA.

Intervention: EVT after IV tPA with CTP-selected patients

EVT in patients with target perfusion mismatch on CTP, after IV tPA.

Intervention: Solitaire stent retriever + IV tPA within 6h

EVT with Solitaire device in anterior LVO patients who received IV tPA.

Intervention: Solitaire stent retriever within 8h

EVT in anterior LVO within 8 hours. Confirmed benefit across pre-specified subgroups.

EVT 6–24h with perfusion/clinical mismatch

EVT is recommended for eligible patients 6–24h from LKW who meet DAWN or DEFUSE 3 mismatch criteria. MR CLEAN-LATE extended the evidence base with CTP selection.

AHA/ASA 2026, §4.7.2 (DAWN, DEFUSE 3, MR CLEAN-LATE)

Intervention: EVT 6–24h with clinical-core mismatch (Trevo device)

Extended EVT window to 24h using clinical-core mismatch on CTP/DWI. Paradigm-shifting trial.

Intervention: EVT 6–16h with perfusion mismatch

EVT in 6–16h window selected by automated perfusion mismatch (RAPID software).

Intervention: EVT 6–24h with collateral-based CTA selection

EVT in the late window (6–24h) using collateral flow on CTA rather than perfusion-software selection. Netherlands multicenter phase 3 trial (n=502 mITT, 535 randomized). Specifically excluded DAWN/DEFUSE-3-eligible patients.

EVT for large ischemic core (ASPECTS 3-5)

EVT is recommended for patients with large ischemic core (ASPECTS 3-5 on CTP/DWI, or core ≥50 mL) within 24h of onset (SELECT2, ANGEL-ASPECT, RESCUE-Japan LIMIT: 0–24h; TENSION: 0–12h). Caution: SELECT2 found ≥26 mL severe hypodensity on NCCT (≤26 HU) was associated with no benefit; TESLA (NCCT-only selection) was neutral — advanced imaging (CTP or DWI) preferred for patient selection when feasible.

AHA/ASA 2026, §4.7.2 (SELECT2, ANGEL-ASPECT, RESCUE-Japan LIMIT, TENSION)

EVT for very large core (ASPECTS 0-2)

EVT can be beneficial for patients with ASPECTS 0-2, though evidence is limited. Underrepresented: age >80, vessel tortuosity, seizures at onset, intracranial stenosis, life expectancy <6 months.

AHA/ASA 2026, §4.7.2

EVT for patients with pre-mRS 2

EVT can be beneficial for patients with pre-stroke mRS of 2 (slight disability). Treatment should be individualized based on patient goals and baseline function.

AHA/ASA 2026, §4.7.2

EVT for patients with pre-mRS 3-4

EVT may be reasonable for patients with pre-stroke mRS 3-4 (moderate-severe disability). Limited evidence; individualized decision based on goals of care.

AHA/ASA 2026, §4.7.2

Intervention: EVT for large ischemic core (ASPECTS 3-5 or core 50+ mL)

International RCT (31 centers, 5 countries) showing EVT benefit in large core infarcts previously excluded from trials. Required CTP or DWI for core quantification. Stopped early at 352/560 (63%) after RESCUE-Japan LIMIT results.

Intervention: EVT for large core (ASPECTS 3-5) within 24h

Chinese RCT confirming EVT benefit in large core strokes (ASPECTS 3-5).

Intervention: EVT for large core (ASPECTS 3-5) within 6h (or 24h with mismatch)

Japanese trial confirming EVT benefit in large core strokes.

Intervention: EVT for large core on NCCT or DWI (ASPECTS 3-5) within 11h

EVT for large core selected by NCCT ASPECTS alone (no CTP required). European trial. Stopped early for efficacy.

EVT for basilar artery occlusion

EVT is recommended for basilar occlusion within 24h, NIHSS ≥10, PC-ASPECTS ≥6. Upgraded from IIa to Class I based on ATTENTION (46% vs 23% mRS 0-3) and BAOCHE (46% vs 24% mRS 0-3).

AHA/ASA 2026, §4.7.3 (ATTENTION, BAOCHE)

EVT for basilar occlusion with lower NIHSS (6–9)

EVT may be considered for basilar occlusion with NIHSS 6–9, PC-ASPECTS ≥6, within 24h. Based on BAOCHE subgroup analysis showing benefit in the NIHSS ≥6 population, though primary endpoint powered for NIHSS ≥10.

AHA/ASA 2026, §4.7.3 (BAOCHE subgroup)

Intervention: EVT for acute basilar artery occlusion within 12h

First positive basilar EVT trial. Significant benefit of thrombectomy for acute basilar occlusion within 12 hours.

Intervention: EVT for basilar artery occlusion 6–24h

EVT for basilar occlusion in extended window (6–24h). Significant benefit with PC-ASPECTS ≥ 6.

EVT for dominant M2 occlusion

EVT can be beneficial for dominant M2 occlusions causing significant deficit (NIHSS ≥6). Upgraded from IIb (2019) to IIa based on ASTER2 and subgroup data.

AHA/ASA 2026, §4.7.2

EVT for mild but disabling LVO stroke (NIHSS <6)

EVT may be reasonable for patients with anterior LVO and NIHSS <6 when the deficit is functionally disabling (e.g., isolated aphasia, dominant-hand weakness in a surgeon). Individualize based on deficit impact, patient goals, and procedural risk.

AHA/ASA 2026, §4.7.2