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Clinical Question

When can I give tPA?

Synthesises 15 trials0–3 h classic window through imaging-selected extended window

What does the guideline say?

  • §4.6.1 Thrombolysis Decision-Making· 2026

    In adult patients with AIS with disabling deficits (regardless of NIHSS score) and eligible for IVT, faster treatment improves functional outcomes (COR 1, LOE A). In adult patients with AIS eligible for IVT within 4.5 hours of symptom onset, treatment should be initiated as quickly as possible, avoiding potential delays associated with additional multimodal neuroimaging such as CTA/MRA and CT/MR perfusion imaging (COR 1, LOE B-NR). In eligible adult patients with AIS presenting with mild non-disabling stroke deficits within 4.5 hours, IVT should not be used routinely as it has not shown superiority in improving functional outcomes compared to dual antiplatelet treatment (COR 3 No Benefit, LOE B-R).

    Source: 2026 AHA/ASA Guideline — §4.6.1 (Thrombolysis Decision-Making)

The trials cited in the guideline's supportive text appear below.

Trials in this question· 15

NINDS1995
Alteplase within 3 h improves functional independence (42.6% vs 27.2% mRS 0–1).
+15 / 100NNT 6.5
ECASS III2008
Alteplase benefit extends from 3 h to 4.5 h after onset.
+7 / 100NNT 14
WAKE-UP2018
Alteplase guided by DWI-FLAIR mismatch in wake-up stroke improves mRS 0–1 at 90 d.
NNT 9+11.5% mRS 0–1
PRISMS2018
Alteplase vs aspirin in minor nondisabling stroke shows no functional benefit and sICH 3.2% vs 0%.
No benefitRD −1.1%
EXTEND-IA TNK2018
TNK 0.25 mg/kg achieves more reperfusion before EVT than alteplase 0.9 mg/kg in LVO patients within 4.5h.
Superior22% vs 10% reperfusion
EXTEND2019
Alteplase 4.5–9 h with perfusion-selected imaging improves recovery.
+6 / 100NNT 17
AcT2022
Tenecteplase 0.25 mg/kg non-inferior to alteplase in routine IVT within 4.5 h.
NI metRD +2.1%
NOR-TEST 2 (Part A)2022
Tenecteplase 0.4 mg/kg in moderate-severe stroke caused 6× more sICH and 3× more deaths vs alteplase.
HarmOR 0.45 mRS 0–1
TWIST2023
Non-contrast CT-only selection of wake-up stroke for tenecteplase failed to show benefit.
NeutralOR 1.18
ARAMIS2023
DAPT non-inferior to alteplase for minor nondisabling stroke at 90 d (93.8% vs 91.4%).
NI metRD +2.3%
THAWS2020
Japan-specific 0.6 mg/kg alteplase for DWI-FLAIR mismatch wake-up stroke showed no benefit; underpowered.
Neutral−1.2% mRS 0–1
ORIGINAL2024
Tenecteplase 0.25 mg/kg noninferior to alteplase within 4.5 h (mRS 0–1 72.7% vs 70.3%).
NI metRR 1.03 (0.97–1.09)
TIMELESS2024
IV tenecteplase 4.5–24 h with perfusion mismatch did not improve mRS shift; not a verdict against late IVT broadly.
NeutralOR 1.13
TRACE-III2024
IV tenecteplase 4.5–24 h with perfusion mismatch in EVT-ineligible LVO improves mRS 0–1 at 90 d.
NNT 11+8.8% mRS 0–1
RAISE2024
Reteplase superior to alteplase for mRS 0–1 at 90 d (79.5% vs 70.4%; P=0.002).
NNT 11RR 1.13

Related questions

Tenecteplase or alteplase?

head-to-head IVT comparisons across geographies, dose, and time-window extensions

Perfusion imaging or non-contrast CT for late-window selection?

evolution from CT-perfusion / MRI mismatch (DAWN, DEFUSE-3) to plain-CT and MRI ASPECTS selection (RESCUE-Japan LIMIT, LASTE, SELECT2, ANGEL-ASPECT)

Minor non-disabling stroke. Alteplase, DAPT, or aspirin?

the trade-off between thrombolysis benefit, DAPT noninferiority, and aspirin baseline in mild stroke

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