Tenecteplase vs Alteplase in Acute Ischemic Stroke
Tenecteplase at 0.25 mg/kg as a single IV bolus is a reasonable alternative to alteplase for acute ischemic stroke, particularly in patients with large vessel occlusions, offering equivalent safety and efficacy with superior workflow advantages. 1, 2
Current Guideline Recommendations
The American Heart Association/American Stroke Association (2018) states 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), though this represents a weaker recommendation than alteplase's Class I indication. 1, 2 However, more recent evidence suggests broader applicability, particularly for large vessel occlusions where tenecteplase at 0.25 mg/kg demonstrates superior recanalization and improved 3-month outcomes compared to alteplase. 2, 3
Key Practical Differences
Administration
- Alteplase: 0.9 mg/kg (maximum 90 mg) given as 10% bolus over 1 minute, then 90% infusion over 60 minutes 4, 1
- Tenecteplase: 0.25 mg/kg (maximum 25 mg) as a single IV bolus 2
The single-bolus administration of tenecteplase offers significant workflow advantages over alteplase's 1-hour infusion, particularly beneficial in centers considering endovascular therapy or patient transfer. 1, 2 This practical advantage reduces nursing burden and medication errors without compromising outcomes.
Pharmacologic Properties
Tenecteplase has a longer half-life (90-130 minutes vs. alteplase's shorter duration), greater fibrin specificity, and higher resistance to plasminogen activator inhibitor-1, potentially providing superior lysis with fewer hemorrhagic complications. 1, 5, 3
Efficacy Evidence
Meta-analyses of randomized trials (1585 patients) demonstrate tenecteplase noninferiority in disability-free 3-month outcomes and superiority in recanalization of large vessel occlusions, without increases in symptomatic intracranial hemorrhage or mortality. 3 The evidence base includes four phase 2 and one phase 3 study comparing tenecteplase to alteplase. 3
For large vessel occlusions specifically, the 0.25 mg/kg dose shows superior recanalization and improved 3-month outcomes relative to alteplase. 2, 3 This makes tenecteplase particularly attractive for patients with confirmed large vessel occlusions on initial imaging.
Safety Profile
Both agents share identical contraindications including intracranial hemorrhage, recent significant trauma or surgery (within 3 months for head trauma), uncontrolled hypertension (>185/110 mmHg), and active bleeding. 4, 1, 2
Symptomatic intracranial hemorrhage rates are comparable between tenecteplase and alteplase, with no significant safety differences demonstrated in pooled analyses. 3 The 2.4% symptomatic ICH rate for alteplase in the 3-4.5 hour window (vs 0.2% placebo) provides context for expected hemorrhage risk. 6
Time Window Considerations
Both agents are approved for use within 3-4.5 hours of symptom onset. 4, 1 Treatment should be initiated as quickly as possible, as time to treatment is strongly associated with outcomes (Class I, Level of Evidence A). 4 The benefit decreases as time from onset increases, with greatest benefit achieved with early treatment. 7
For the 3-4.5 hour window, alteplase has established efficacy (52.4% favorable outcome vs 45.2% placebo, OR 1.34,95% CI 1.02-1.76). 6 Tenecteplase trials in this extended window are ongoing. 3
Clinical Decision Algorithm
For patients with large vessel occlusion on initial imaging: Tenecteplase 0.25 mg/kg is preferred given superior recanalization rates and improved outcomes. 2, 3
For patients with minor neurological impairment and no major intracranial occlusion: Tenecteplase is a reasonable alternative per AHA/ASA guidelines. 1, 2
For all other eligible acute ischemic stroke patients within 4.5 hours: Either agent is appropriate, with tenecteplase offering workflow advantages without compromising safety or efficacy. 1, 3
Patients eligible for endovascular therapy should still receive IV thrombolysis (either agent) without delay (Class I, Level of Evidence A), as bridging therapy improves outcomes. 1
Important Caveats
The AHA/ASA guidelines state that the benefit of IV fibrinolytic agents other than alteplase and tenecteplase is unproven; therefore, their administration is not recommended outside clinical trials. 1 Streptokinase specifically should never be used due to high hemorrhage rates. 2
Careful patient selection remains critical regardless of which agent is chosen, with strict adherence to inclusion/exclusion criteria to minimize hemorrhagic complications. 4, 1 Hyperglycemic patients have substantially increased risk of symptomatic cerebral hemorrhage with thrombolysis. 4
The 0.4 mg/kg tenecteplase dose has been studied but shows no advantage over 0.25 mg/kg, making the lower dose the recommended option. 3