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

Tenecteplase vs Alteplase for Acute Ischemic Stroke Management

Tenecteplase is a suitable alternative to alteplase for acute ischemic stroke treatment, offering similar safety and efficacy with practical advantages of single-bolus administration versus alteplase's 1-hour infusion. 1

Key Differences Between Tenecteplase and Alteplase

Pharmacological Differences

• Tenecteplase is a genetically modified tissue plasminogen activator (tPA) with structural modifications: substitution of threonine 103 with asparagine, asparagine 117 with glutamine, and a tetra-alanine substitution at amino acids 296–299 2
• Tenecteplase has greater fibrin specificity than alteplase, which decreases systemic activation of plasminogen and resulting degradation of circulating fibrinogen 2, 3
• Tenecteplase has a longer half-life (90-130 minutes) compared to alteplase, allowing for single-bolus administration rather than the 1-hour infusion required for alteplase 4, 2

Administration Differences

• Alteplase is administered as a bolus (10% of total dose) followed by the remaining dose as an infusion over 1 hour at 0.9 mg/kg (maximum 90 mg) 4
• Tenecteplase is administered as a single intravenous bolus at 0.25 mg/kg or 0.4 mg/kg, providing significant workflow advantages in acute stroke settings 4, 1

Efficacy Comparison

Clinical Outcomes

• The 2018 AHA/ASA guidelines state that tenecteplase administered as a 0.4-mg/kg single IV bolus has not been proven to be superior or noninferior to alteplase but might 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) 4
• Recent evidence from the ORIGINAL trial (2024) demonstrated that tenecteplase 0.25 mg/kg was noninferior to alteplase with respect to excellent functional outcome (mRS score of 0 or 1) at 90 days (72.7% vs 70.3%) 1
• Meta-analyses suggest that 0.25 mg/kg tenecteplase may significantly improve excellent functional outcome at 3 months compared to alteplase (OR 1.16,95% credible interval 1.02-1.32) 5

Vessel Recanalization

• Tenecteplase appears to have potentially superior efficacy in large vessel recanalization compared to alteplase, which may be particularly beneficial in patients with large vessel occlusions 3
• This improved recanalization may be attributed to tenecteplase's enhanced fibrin specificity 2, 3

Safety Comparison

Bleeding Risk

• Symptomatic intracerebral hemorrhage rates are similar between tenecteplase and alteplase (1.2% for both groups in the ORIGINAL trial) 1
• Meta-analyses show no significant difference in symptomatic intracranial hemorrhage between tenecteplase and alteplase (OR 1.12; 95% CI 0.79-1.59) 5

Mortality

• Recent evidence suggests tenecteplase may be associated with lower all-cause mortality compared to alteplase (4.6% vs 5.8% in the ORIGINAL trial) 1
• Meta-analyses support this finding, showing tenecteplase probably reduces all-cause mortality compared to alteplase (adjusted OR 0.44; 95% CI 0.30-0.64) 5

Practical Considerations

Workflow Advantages

• The single-bolus administration of tenecteplase offers significant workflow advantages over alteplase's 1-hour infusion, particularly in centers considering endovascular therapy or patient transfer 4
• This simpler administration may reduce door-to-needle times and facilitate more rapid initiation of additional treatments 4

Cost Considerations

• Tenecteplase has been reported to have lower costs compared to alteplase, which may be an additional consideration in resource-limited settings 3, 6

Current Guideline Recommendations

• The 2018 AHA/ASA guidelines state that tenecteplase might 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) 4
• Patients eligible for IV alteplase should receive IV alteplase even if endovascular therapies are being considered (Class I, Level of Evidence A) 4
• The benefit of IV fibrinolytic agents other than alteplase and tenecteplase is unproven; therefore, their administration is not recommended outside a clinical trial 4

Clinical Decision Making

When to Consider Tenecteplase Over Alteplase

• In patients with minor neurological impairment and no major intracranial occlusion 4
• When single-bolus administration offers significant workflow advantages, such as in centers considering endovascular therapy or patient transfer 4
• In settings where the practical advantages of tenecteplase (single-bolus administration, potential cost savings) outweigh the longer clinical experience with alteplase 3, 6

Cautions and Contraindications

• Both agents share similar contraindications including evidence of intracranial hemorrhage, recent significant trauma or surgery, and uncontrolled hypertension 4
• Careful patient selection remains critical regardless of which thrombolytic agent is chosen 4

Future Directions

• Ongoing trials are investigating tenecteplase in delayed treatment windows and in combination with thrombectomy 3
• Tenecteplase may eventually complement or replace alteplase as the standard thrombolytic agent for acute ischemic stroke treatment 4