What is the difference between tenecteplase and tPA (tissue plasminogen activator) in the management of acute ischemic stroke?

Tenecteplase vs tPA for Acute Ischemic Stroke

Tenecteplase 0.25 mg/kg is now a suitable alternative to alteplase (tPA) for acute ischemic stroke within 4.5 hours of symptom onset, offering superior functional outcomes with similar safety and significant practical advantages. 1, 2

Key Clinical Differences

Administration and Pharmacology

• Tenecteplase is given as a single IV bolus over 5-10 seconds at 0.25 mg/kg (maximum 25 mg), while alteplase requires a 10% bolus followed by 1-hour infusion at 0.9 mg/kg (maximum 90 mg) 3, 4
• Tenecteplase has a longer half-life (90-130 minutes) and greater fibrin specificity than alteplase, eliminating the need for prolonged infusion 4, 5
• The single-bolus administration offers significant workflow advantages, particularly when considering endovascular therapy or patient transfer 4

Efficacy Outcomes

• Tenecteplase demonstrates superiority over alteplase for excellent functional outcomes (mRS 0-1 at 90 days): 72.7% vs 70.3%, with a risk ratio of 1.05 (95% CI 1.01-1.10) 1, 2
• Tenecteplase also shows reduced disability at 3 months (≥1-point reduction across all mRS scores) compared to alteplase 1
• For arterial recanalization prior to mechanical thrombectomy, tenecteplase achieves superior reperfusion rates (22% vs 10% substantial reperfusion) 6
• Good functional outcomes (mRS 0-2) are similar between agents 1

Safety Profile

• Both agents have equivalent safety profiles with similar rates of symptomatic intracerebral hemorrhage (approximately 1.2% for both) 1, 2
• Major bleeding rates are comparable: 18% for alteplase vs 18.1% for tenecteplase 7
• 90-day mortality is similar: 4.6% for tenecteplase vs 5.8% for alteplase 2
• Both share identical contraindications including intracranial hemorrhage, recent significant trauma/surgery, and uncontrolled hypertension 3, 4

Current Guideline Recommendations

American Heart Association/American Stroke Association Position

• Tenecteplase may be considered as an alternative to alteplase in patients with minor neurological impairment and no major intracranial occlusion (Class IIb, Level of Evidence B-R) 3, 4
• The 0.25 mg/kg dose is specifically recommended for large vessel occlusions based on superior recanalization and improved 3-month outcomes 3
• Patients eligible for IV alteplase should still receive thrombolysis even if endovascular therapy is being considered (Class I, Level of Evidence A) 4

Canadian Stroke Best Practices

• As of 2018, further evidence from ongoing trials was required before recommending changes to clinical practice, though tenecteplase showed promise for superior recanalization 6
• The EXTEND-IA TNK trial demonstrated higher reperfusion rates but was not powered for clinical outcomes 6

Practical Implementation

Dosing Specifics

• Tenecteplase: 0.25 mg/kg as single IV bolus (maximum 25 mg) over 5-10 seconds 3, 7
• Alteplase: 0.9 mg/kg (maximum 90 mg) with 10% as bolus over 1 minute, remainder over 60 minutes 4

Cost Considerations

• Tenecteplase offers substantial cost savings, with one institution reporting over $40,000 in medication savings during an 18-month period 8
• The ease of single-bolus administration reduces nursing time and potential medication errors 6

Time-to-Treatment

• Both agents should be initiated as soon as possible after CT scan, with every effort to minimize door-to-needle times 3
• Door-to-needle times are comparable between agents, though some data suggest slight advantages with tenecteplase when outliers are excluded 8

Critical Caveats

Evidence Limitations

• The 2018 Canadian guidelines noted that tenecteplase trials were not powered to demonstrate effects on clinical outcomes, requiring additional evidence 6
• However, the 2024 ORIGINAL trial with 1,465 patients definitively established noninferiority and suggested superiority for excellent functional outcomes 2
• The updated 2024 meta-analysis of 11 RCTs (7,545 patients) confirms tenecteplase superiority for excellent functional outcomes while maintaining similar safety 1

Agents to Avoid

• Streptokinase should never be used due to unacceptably high hemorrhage rates 6
• Other agents (reteplase, urokinase, anistreplase) lack extensive testing in stroke and are not recommended 6

Special Populations

• Both agents require careful consideration in patients on novel oral anticoagulants (dabigatran, rivaroxaban, apixaban), where reliable assays and clinical history are critical 6
• The evidence base for tenecteplase includes both original formulations and biocopies (recombinant variants), with statistical significance for excellent outcomes retained for original tenecteplase 1