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

Tenecteplase in Acute Ischemic Stroke

Tenecteplase (0.25 mg/kg as a single IV bolus, maximum 25 mg) is a suitable alternative to alteplase for acute ischemic stroke within 4.5 hours of symptom onset, offering equivalent efficacy with the practical advantage of single-bolus administration versus alteplase's 1-hour infusion. 1, 2, 3

Primary Recommendation

For patients with acute ischemic stroke presenting within 4.5 hours of symptom onset, tenecteplase 0.25 mg/kg (maximum 25 mg) may be considered as an alternative to alteplase 0.9 mg/kg, particularly in patients with minor neurological impairment and no major intracranial occlusion. 1, 2

• The American Heart Association/American Stroke Association provides a Class IIb recommendation (Level of Evidence B-R) for tenecteplase as an alternative to alteplase in selected patients 1, 2
• The 2024 ORIGINAL trial (the most recent high-quality evidence) demonstrated noninferiority of tenecteplase to alteplase, with 72.7% achieving excellent functional outcome (mRS 0-1) versus 70.3% with alteplase 3
• Both agents showed identical symptomatic intracranial hemorrhage rates (1.2% each) and similar 90-day mortality (4.6% vs 5.8%) 3

Dosing and Administration

Tenecteplase is administered as a single weight-based IV bolus of 0.25 mg/kg (maximum dose 25 mg), which should be given as rapidly as possible after CT scan confirmation of eligibility. 1, 2

• The longer half-life of tenecteplase (90-130 minutes) allows single-bolus administration, compared to alteplase's requirement for 10% bolus followed by 90% infusion over 60 minutes 1, 2
• This single-bolus administration offers significant workflow advantages, particularly when endovascular therapy or patient transfer is being considered 1, 2
• The 0.25 mg/kg dose is specifically recommended for large vessel occlusions based on superior recanalization rates (22% vs 10% substantial reperfusion with alteplase) 1

Time Window and Patient Selection

Tenecteplase should be administered within 4.5 hours of symptom onset in carefully selected patients who meet eligibility criteria similar to those established for alteplase. 4, 1, 3

• For the 0-3 hour window: IV thrombolysis should be offered to patients meeting NINDS inclusion/exclusion criteria (Level A recommendation for alteplase) 4
• For the 3-4.5 hour window: IV thrombolysis should be considered in patients meeting ECASS III criteria (Level B recommendation) 4
• The ORIGINAL trial included patients with NIHSS scores 1-25 who were symptomatic for at least 30 minutes without significant improvement 3

Contraindications and Safety Profile

Both tenecteplase and alteplase share identical contraindications, including evidence of intracranial hemorrhage, recent significant trauma or surgery, and uncontrolled hypertension. 1, 2

• Absolute increase in symptomatic intracranial hemorrhage risk is approximately 6% (7% with thrombolysis vs 1% without), yielding a number needed to harm of 17 4
• Relative contraindications include recent internal bleeding (within 2-4 weeks), noncompressible vascular punctures, pregnancy, active peptic ulcer, and current oral anticoagulant use 2
• Both agents require careful consideration in patients on novel oral anticoagulants (dabigatran, rivaroxaban, apixaban), where reliable assays and clinical history are critical 1

Clinical Outcomes and Evidence Quality

Meta-analysis of multiple trials demonstrates that tenecteplase 0.25 mg/kg achieves complete recanalization more effectively than alteplase (RR 1.27) while maintaining similar safety profiles. 5, 6

• Network meta-analysis ranking places tenecteplase 0.25 mg/kg as optimal for excellent functional outcomes (P-score = 0.86), while alteplase ranks best for minimizing symptomatic intracranial hemorrhage (P-score = 0.71) 6
• The 2023 meta-analysis of 3,707 patients confirmed tenecteplase leads to significantly better complete recanalization without differences in mortality, intracranial hemorrhage, or parenchymal hematoma 5
• The NOR-TEST trial (2017) showed no superiority of tenecteplase 0.4 mg/kg over alteplase, but this higher dose is not the recommended regimen 7

Practical Implementation

Tenecteplase reduces nursing time and potential medication errors through single-bolus administration, making it particularly advantageous in centers performing endovascular therapy or requiring patient transfers. 1

• Treatment should be initiated as soon as possible after patient arrival and CT scan, with door-to-needle time targets of 30 minutes 1
• Patients eligible for IV thrombolysis should receive treatment even if endovascular therapies are being considered (Class I, Level A recommendation) 1
• Shared decision-making should include discussion of potential benefits (NNT of 8-14 for favorable outcomes) and harms (NNH of 17 for symptomatic ICH) 4

Agents NOT Recommended

Streptokinase should never be used for acute ischemic stroke due to unacceptably high hemorrhage rates, and other fibrinolytic agents (reteplase, urokinase, anistreplase) lack adequate evidence. 1, 2

• The American Heart Association states that the benefit of IV fibrinolytic agents other than alteplase and tenecteplase is unproven and should not be used outside clinical trials 1

Critical Caveat

The effectiveness of both tenecteplase and alteplase has been best established in institutions with systems in place to safely administer thrombolytic therapy, including rapid imaging, neurological assessment, and management of complications. 4