What is the role of IV tenecteplase (tissue plasminogen activator) in ischemic stroke prior to mechanical thrombectomy?

IV Tenecteplase in Ischemic Stroke Prior to Mechanical Thrombectomy

Tenecteplase at a dose of 0.25 mg/kg is recommended over alteplase as the preferred thrombolytic agent prior to mechanical thrombectomy in patients with large vessel occlusion ischemic stroke within 4.5 hours of symptom onset. 1

Evidence-Based Rationale

Efficacy and Safety Profile

Tenecteplase has emerged as an effective alternative to alteplase for thrombolysis prior to mechanical thrombectomy, with several key advantages:

• Superior reperfusion rates: Tenecteplase achieves higher rates of early reperfusion before thrombectomy compared to alteplase (22% vs 10%) 2
• Improved functional outcomes: Patients receiving tenecteplase demonstrate better 90-day functional outcomes with a median modified Rankin Scale score of 2 vs 3 for alteplase 2
• Comparable safety profile: Symptomatic intracerebral hemorrhage rates are similar between tenecteplase and alteplase (approximately 1% in both groups) 2

Optimal Dosing

The optimal dose of tenecteplase has been established:

• 0.25 mg/kg (maximum 25 mg) is the recommended dose 1
• Higher doses (0.40 mg/kg) do not provide additional benefit in reperfusion rates (19.3% for both doses) and may potentially increase bleeding risk 3

Practical Advantages

Tenecteplase offers significant practical advantages over alteplase:

• Single bolus administration versus the 1-hour infusion required for alteplase 4
• Improved workflow efficiency with reduced door-to-needle times (140 min vs 165 min) 5
• Particularly valuable in time-sensitive scenarios such as mobile stroke units or during healthcare system constraints 1, 5

Implementation Algorithm

1. Patient Selection:

   • Confirm ischemic stroke with large vessel occlusion (internal carotid, basilar, or middle cerebral artery)
   • Ensure patient is within 4.5 hours of symptom onset
   • Verify eligibility for IV thrombolysis (no contraindications)

2. Dosing and Administration:

   • Calculate tenecteplase dose at 0.25 mg/kg (maximum 25 mg)
   • Administer as a single IV bolus
   • Proceed to mechanical thrombectomy without delay

3. Post-Administration Monitoring:

   • Monitor for signs of intracerebral hemorrhage
   • Assess for early neurological improvement
   • Proceed with planned mechanical thrombectomy regardless of clinical improvement

Important Caveats and Considerations

• Time window limitations: Tenecteplase, like alteplase, should not be administered beyond 4.5 hours from symptom onset unless advanced imaging selection criteria are met 4
• Contraindications: Standard contraindications for thrombolysis apply (recent surgery, active bleeding, coagulopathy)
• Mechanical thrombectomy timing: Do not delay thrombectomy to observe for clinical response to tenecteplase

Historical Context and Evolution of Guidelines

It's important to note that earlier guidelines (2012) suggested against mechanical thrombectomy (Grade 2C) 4, but this recommendation has been superseded by more recent evidence. The 2018 guidelines began acknowledging the potential role of tenecteplase as an alternative to alteplase 4, and subsequent research has further solidified its position.

The most recent European Stroke Organisation recommendations (2023) provide strong support for tenecteplase use, particularly in patients with large vessel occlusion planned for mechanical thrombectomy 1.