Intra-arterial thrombolysis

David Goldemund M.D.
Updated on 03/01/2024, published on 16/09/2022
  • intra-arterial thrombolysis (IAT) involves the administration of a thrombolytic agent via catheter directly into the occluded artery
  • several trials using prourokinase (MELT, PROACT) and alteplase ( IMS-3, SYNTHESIS) showed the benefit of this therapy
    • MELT  The Middle Cerebral Artery Embolism Local Fibrinolytic Intervention Trial) 
    • PROACT-2  (Prolyse in Acute Cerebral Thromboembolism)
    • IMS 3 (Interventional Management of Stroke trial)
      • demonstrated that the combined IV+IA approach to recanalization may be more effective than standard IVT alone for moderate to severe strokes, with a similar safety profile
  • alteplase (tPA) is used in clinical practice
  • the dosage is not standardized
  • the standard therapeutic time window for IAT was 0-6h; studies with advanced imaging (showing penumbra) are not available (the individual window can theoretically be derived from IVT studies – but this is not discussed in the guidelines)


  • indications are the same as for mechanical thrombectomy (MT)
  • IAT is now rarely used as a stand-alone procedure; MT is preferred as a more potent recanalization technique
  • IAT can be performed:
    • when the thrombus is inaccessible for mechanical recanalization (extreme kinking, etc.)
    • to treat distal embolization (incl. those occurring during embolectomy)  (Khatri, 2022)  [Kaesmacher, 2019]
    • as a rescue procedure after failed MT; the efficacy of MT followed by IAT was reported in the CHOICE trial  (Zaidi,2019)

CHOICE trial

  • The CHOICE trial was a Phase 2b randomized, double-blind, placebo-controlled trial conducted from December 2018 through May 2021 in seven stroke centers in Catalonia, Spain
  • It aimed to investigate whether adjunct intra-arterial alteplase after thrombectomy improves outcomes following reperfusion in patients with large vessel occlusion acute ischemic stroke
  • the trial included 121 patients treated with thrombectomy within 24 hours after stroke onset. Participants were randomized to receive intra-arterial alteplase (0.225 mg/kg; maximum dose, 22.5 mg) infused over 15-30 minutes (61 patients) or placebo (52 patients)
  • the primary outcome was the difference in the proportion of patients achieving a score of 0 or 1 on the 90-day modified Rankin Scale. Results showed that 59.0% of participants with alteplase and 40.4% with placebo achieved this score
  • the study was terminated early due to the COVID-19 pandemic, affecting placebo availability and enrollment rate
  • these findings should be interpreted as preliminary and require replication due to study limitations


Apart from the usual contraindications to thrombolysis :

  • arterial dissection
  • proximal (usually carotid) stenosis or significant coiling preventing microcatheter delivery to the occluded segment
  • extensive signs of ischemia on CT or absence of penumbra on CT perfusion


Dosing according to original IAT protocols

  • dilute ACTILYSE20 mg with 50mL NS (solution: 1mL=0.4mg tPA)
  • the dosage is not standardized; most commonly in the range of 22-69 mg  [Qureshi, 2000]
  • IAT after the previous IVT
    • usually, 20mg of tPA is administered IA within 1 hour
      • initial bolus 5mg followed by 45mL/h infusion
      • control super-selective angiograms are performed every 15 minutes until thrombus dissolution or until a maximum total dose of 20mg is reached
      • the combination of full-dose IVT followed by thrombectomy or IAT at a dose of 20mg given within 1 hour appears to be safe [Hashem, 2007]
    • IAT with a dose of 69mg has also been reported to be safe after previous IVT  [Hassan, 2012]
  • IAT without previous IVT
    • usually, 40 mg of tPA is administered over 2 hours
      • initial bolus 5ml, followed by 45mL/h infusion in the first hour and 50 mL/h in the second hour
      • control super-selective angiograms are performed every 15 minutes until thrombus dissolution or until a maximum total dose of 40mg is reached
    • in the SYNTHESIS trial, even a dose of 0.9 mg/kg was administered (without prior IVT)
    • in the CHOICE trial, a dose of 0.225 mg/kg was used; a maximum dose of 22.5 mg, administered as a 15-30 minute infusion
  • if recanalization is achieved,  wait 15-20 minutes and perform a control angiogram to rule out early reocclusion

IAT after previous mechanical thrombectomy

  • tPA dosing according to the CHOICE trial – ALTEPLASE 0.225 mg/kg; max 22.5 mg, administered within 15-30 minutes in patients with TICI 2b-3
Successful intra-arterial thrombolysis of occluded basilar artery

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Intra-arterial thrombolysis