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Neurology›Clinical Question·Updated Jul 4, 2026·v1

thrombolysis for acute ischemic stroke within 4.5 hours [Grok-4.3]

Intravenous thrombolysis with [[alteplase]] is recommended for eligible adults with acute ischemic stroke within 4.5 hours of onset when standard inclusion and exclusion criteria are met [4]. The magnitude of benefit on functional independence ([[mRS]] 0-2 at 90 days) and risks of symptomatic intracranial hemorrhage

Moderate Evidence21 references·974 words·4 min read·v1
Intravenous thrombolysis with [[alteplase]] is recommended for eligible adults with acute ischemic stroke within 4.5 hours of onset when standard inclusion and exclusion criteria are met [4]. The magnitude of benefit on functional independence ([[mRS]] 0-2 at 90 days) and risks of symptomatic intracranial hemorrhage or mortality versus no thrombolysis were not quantified in the retrieved evidence.

Board Review — High Yield

  • •IV thrombolysis with [[alteplase]] recommended within 4.5 h if criteria met [4]
  • •AcT trial showed equivalent SAE rates for tenecteplase and alteplase inside 4.5 hours [7]
  • •AcT trial showed no difference in serious adverse event rates or types between tenecteplase and alteplase within 4.5 hours.
  • •Minor acute ischemic stroke shows no functional benefit and elevated harm with thrombolysis in RCT meta-analysis [2].
  • •Tirofiban infusion after thrombolysis increased mRS 0-1 rates (65.9% vs 54.9%) with low but nonzero symptomatic ICH [16].

Deep Dive — Evidence Details

References

  1. [1]

    Gonçalves OR, Tudella GCN, Cardoso LJC et al.. “Magnetic Resonance Imaging/Diffusion-Weighted Imaging-Guided Versus Perfusion-Guided Intravenous Thrombolysis with Alteplase Beyond 4.5-Hour Window: a Network Meta-Analysis of Randomized Controlled Trials.” Clinical neuroradiology (2026). PMID: 42371037 ↗

    L1SR_MA_RCTCited in: Bottom Line, Background: Evolution of Treatment, Current Evidence and Standard, Applicability and Caveats
  2. [2]

    Teo KSH, Ong JM, Yeo JYP et al.. “Neurology® Journal Club: Meta-Analysis of Randomized Controlled Trials on IV Thrombolysis in Patients With Minor Acute Ischemic Stroke.” Neurology (2026). PMID: 42335433 ↗

    L1SR_MA_RCTCited in: Bottom Line, Background: Evolution of Treatment, Current Evidence and Standard, Applicability and Caveats
  3. [3]

    Gonçalves OR, Scarcia L, Portela JGS et al.. “Tenecteplase Beyond the 4.5-h Window for Patients with Acute Ischemic Stroke: An Updated Meta-Analysis of Randomized Controlled Trials.” CNS drugs (2026). PMID: 42307864 ↗

    L1SR_MA_RCTCited in: Bottom Line, Background: Evolution of Treatment, Current Evidence and Standard, Applicability and Caveats
  4. [4]

    Debette S, Mazighi M, Bijlenga P et al.. “ESO guideline for the management of extracranial and intracranial artery dissection.” European stroke journal (2021). PMID: 34746432 ↗

    L5OTHERCited in: Bottom Line
  5. [5]

    Adams C, Heard K, Kohli Y et al.. “Safety and Efficacy of Nerinetide at Year 1 in Participants Enrolled in ESCAPE-NEXT: A Multicenter, Double-Blind, Randomized Controlled Trial.” Journal of the American Heart Association (2026). PMID: 42333641 ↗

    L1RCTCited in: Bottom Line, Background: Evolution of Treatment, Current Evidence and Standard, Applicability and Caveats
  6. [6]

    Schlemm E, Jensen M, Schell M et al.. “Large Core Stroke Thrombectomy Is Safe and Effective Regardless of Prior Antithrombotic or Thrombolytic Treatment: A Secondary Analysis of the Randomized TENSION Trial.” Journal of the American Heart Association (2026). PMID: 42261979 ↗

    L1RCTCited in: Bottom Line, Background: Evolution of Treatment, Current Evidence and Standard, Applicability and Caveats
  7. [7]

    Appoo A, Ignacio K, Doolan C et al.. “Predictors and Consequences of Serious Adverse Events in Patients Treated With Thrombolysis: A Prespecified Secondary Analysis of the AcT Trial.” Journal of the American Heart Association (2026). PMID: 42261967 ↗

    L1RCTCited in: Bottom Line, Background: Evolution of Treatment, Current Evidence and Standard, Applicability and Caveats, On the Horizon
  8. [8]

    Pensato U, Zhang J, Barakhanov K et al.. “Association of 24-Hour Computed Tomography Infarct Density on Functional Outcomes in Stroke: Secondary Analysis From the AcT Trial.” Journal of the American Heart Association (2026). PMID: 42179273 ↗

    L1RCTCited in: Bottom Line, Background: Evolution of Treatment, Current Evidence and Standard, Applicability and Caveats
  9. [9]

    Ignacio KHD, Pensato U, Bala F et al.. “Effect of time on reperfusion in acute ischemic stroke treated with thrombolysis within the 4.5-hour window: a secondary analysis of the AcT Trial.” Journal of stroke and cerebrovascular diseases : the official journal of National Stroke Association (2026). PMID: 42173266 ↗

    L1RCTCited in: Bottom Line, Background: Evolution of Treatment, Current Evidence and Standard, Applicability and Caveats
  10. [10]

    Hu W, Jing X, Chen Z et al.. “Endovascular Treatment of Medium-Vessel-Occlusion Strokes.” The New England journal of medicine (2026). PMID: 42127389 ↗

    L1RCTCited in: Bottom Line, Current Evidence and Standard, Applicability and Caveats
  11. [11]

    Liu X, Zhang F, Zhang C et al.. “Intravenous Tirofiban After Tenecteplase in Acute Ischemic Stroke: The INSTANT Randomized Clinical Trial.” JAMA (2026). PMID: 42100960 ↗

    L1RCTCited in: Bottom Line, Current Evidence and Standard, Applicability and Caveats
  12. [12]

    Pierot L, Jarayaman M, Szikora I et al.. “Standards of Practice in Acute Ischemic Stroke Intervention International Recommendations.” The Canadian journal of neurological sciences. Le journal canadien des sciences neurologiques (2019). PMID: 30890199 ↗

    L5REVIEW_NARRATIVECited in: Bottom Line
  13. [13]

    Renú A, Fernández-Couto MD, de la Riva P et al.. “Adjunctive Intra-Arterial Alteplase After Successful Thrombectomy for Acute Ischemic Stroke: The CHOICE-2 Randomized Clinical Trial.” JAMA (2026). PMID: 42096239 ↗

    L1RCTCited in: Current Evidence and Standard
  14. [14]

    Wang J, He D, Gu H et al.. “Efficacy and Safety of Reteplase Versus Alteplase in Acute Ischemic Stroke Based on Fibrinogen Levels: The RAISE Trial Subgroup.” Journal of the American Heart Association (2026). PMID: 42089199 ↗

    L1RCTCited in: Current Evidence and Standard
  15. [15]

    Zini A, Vandelli L, Forlivesi S et al.. “Fibrinogen replacement to prevent intracranial hemorrhage in ischemic stroke patients after thrombolysis - a prospective randomized open blinded endpoint trial (FibER): rationale and methods.” Journal of stroke and cerebrovascular diseases : the official journal of National Stroke Association (2026). PMID: 41581534 ↗

    L1RCTCited in: On the Horizon
  16. [16]

    Tao C, Liu T, Cui T et al.. “Early Tirofiban Infusion after Intravenous Thrombolysis for Stroke.” The New England journal of medicine (2025). PMID: 40616232 ↗

    L1RCTCited in: On the Horizon
  17. [17]

    Shawkat A, Barreto AD, Broderick JP et al.. “Comparison of Local and Centrally Adjudicated Modified Rankin Scale Scores in the MOST Trial.” Stroke (2025). PMID: 40123511 ↗

    L1RCTCited in: On the Horizon
  18. [18]

    Singh N, Bala F, Ademola A et al.. “Safety, Functional Disability, Healthcare Utilization, and Quality-of-Life Outcomes in Elderly Receiving Alteplase and Tenecteplase: A Secondary Analysis From the AcT Trial.” Stroke (2025). PMID: 40123483 ↗

    L1RCTCited in: On the Horizon
  19. [19]

    Galinovic I, Fiebach JB, Boutitie F et al.. “Effect of IV Thrombolysis With Alteplase in Patients With Vessel Occlusion in the WAKE-UP Trial.” Neurology (2024). PMID: 39705631 ↗

    L1RCTCited in: On the Horizon
  20. [20]

    Dhillon PS, Butt W, Podlasek A et al.. “Effect of Proximal Blood Flow Arrest During Endovascular Thrombectomy (ProFATE): A Multicenter, Blinded-End Point, Randomized Clinical Trial.” Stroke (2024). PMID: 39697177 ↗

    L1RCTCited in: On the Horizon
  21. [21]

    Ospel JM, Goyal M, Menon BK et al.. “Factors Influencing Nerinetide Effect on Infarct Volume in Patients Without Alteplase in the Randomized ESCAPE-NA1 Trial.” Stroke (2024). PMID: 39648909 ↗

    L1RCTCited in: On the Horizon

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