ISCHEMIC STROKE / ACUTE THERAPY

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

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

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

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

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