What is the role of tenecteplase (tissue plasminogen activator) in the management of acute ischemic stroke?

Tenecteplase in Acute Ischemic Stroke Management

Tenecteplase at 0.25 mg/kg (maximum 25 mg) as a single IV bolus is an effective alternative to alteplase for thrombolysis in acute ischemic stroke patients within 4.5 hours of symptom onset, with comparable efficacy and safety profiles. 1, 2

Efficacy and Safety Profile

Tenecteplase is a genetically modified tissue plasminogen activator (tPA) with several advantages over alteplase:

• Higher fibrin specificity
• Longer half-life
• Single-bolus administration (versus alteplase's 1-hour infusion)
• Comparable rates of symptomatic intracerebral hemorrhage (approximately 1.2%) 1

Recent high-quality evidence from the ORIGINAL trial (2024) demonstrated that tenecteplase (0.25 mg/kg) was noninferior to alteplase with respect to excellent functional outcomes at 90 days in patients with acute ischemic stroke treated within 4.5 hours of symptom onset 2.

Time Windows and Patient Selection

The use of tenecteplase follows similar time windows as established for alteplase:

• Within 3 hours of symptom onset (Level A recommendation) 3
• Between 3-4.5 hours after symptom onset (Level B recommendation) 3

Clinical Scenarios Where Tenecteplase May Be Particularly Beneficial

1. Patients requiring urgent transport to comprehensive stroke centers for endovascular therapy
2. Patients evaluated at comprehensive stroke centers who are eligible for endovascular intervention
3. Patients with mild neurological deficit and no significant intracranial occlusion 1

The EXTEND-IA TNK trial showed that tenecteplase was superior to alteplase with respect to arterial recanalization when given prior to mechanical thrombectomy, with 22% versus 10% achieving substantial reperfusion 3.

Contraindications

Absolute contraindications for tenecteplase include:

• Previous intracranial hemorrhage
• Known structural vascular cerebral lesion
• Known malignant intracranial neoplasm
• Ischemic stroke in the last 3 months
• Suspected aortic dissection
• Active bleeding or hemorrhagic diathesis
• Significant head or facial trauma in the last 3 months
• Intracranial or intra-spinal surgery in the last 2 months
• Uncontrolled severe hypertension (SBP >180 mmHg or DBP >110 mmHg) 1

Implementation Considerations

When implementing tenecteplase for acute stroke:

• Administration should be done as quickly as possible after the decision to perform thrombolysis 1
• The recommended dose is 0.25 mg/kg (maximum 25 mg) as a single IV bolus 1
• Patients should be monitored for complications including symptomatic intracerebral hemorrhage and angioedema 4

Emerging Evidence and Future Directions

Several ongoing trials are investigating tenecteplase in various stroke scenarios:

• TASTE, TEMPO-2, TWIST, and ATTEST-2 trials are examining tenecteplase's efficacy and safety 3
• The MOST trial has been adapted to include tenecteplase as standard-of-care thrombolytic therapy, reflecting its increasing adoption 3

Pitfalls and Caveats

1. Do not use tenecteplase in wake-up stroke patients selected only by non-contrast CT, even with favorable perfusion, as current evidence does not support this practice 1

2. Effectiveness of thrombolysis is less well established in institutions without proper systems in place to safely administer the medication 3

3. Time is critical - once the decision is made to administer thrombolysis, the patient should be treated as rapidly as possible 3

4. Shared decision-making between the patient (and/or surrogate) and healthcare team should include discussion of potential benefits and harms prior to administering thrombolysis 3

Tenecteplase's practical advantages of single-bolus administration and comparable safety profile make it an increasingly preferred option for acute ischemic stroke thrombolysis, particularly in settings where rapid treatment and transfer for mechanical thrombectomy may be necessary.