Is tenekteplase (tPA) indicated in a wake-up stroke with favorable perfusion?

Tenecteplase in Wake-Up Stroke with Favorable Perfusion

Tenecteplase should not be administered in wake-up stroke patients selected only by non-contrast CT, even with favorable perfusion, as current evidence does not support this practice. 1

Current Evidence on Wake-Up Stroke Treatment

Guidelines and Recommendations

• The American Heart Association/American Stroke Association (AHA/ASA) 2018 guidelines mention that patients with unknown symptom onset ("wake-up strokes") may benefit from alteplase if a DWI/FLAIR mismatch is present on MRI 2
• Tenecteplase is mentioned in guidelines as a potential alternative to alteplase, but primarily for patients with minor neurological impairment and no major intracranial occlusion (Class IIb, Level of Evidence B-R) 2
• The guidelines do not specifically recommend tenecteplase for wake-up stroke based on perfusion imaging alone

Recent Clinical Trial Evidence

• The TWIST trial (2023) specifically evaluated tenecteplase in wake-up stroke patients selected by non-contrast CT and found that treatment with tenecteplase was not associated with better functional outcomes at 90 days compared to standard care 1
• While the number of symptomatic hemorrhages was similar to previous trials using advanced imaging selection, the efficacy was not demonstrated

Decision Algorithm for Wake-Up Stroke Treatment

1. First determine if patient meets criteria for standard thrombolysis with advanced imaging:

   • If DWI/FLAIR mismatch is present on MRI, consider alteplase per WAKE-UP trial results 2
   • If large vessel occlusion is present with salvageable tissue on perfusion imaging AND patient is within thrombectomy window, prioritize mechanical thrombectomy 2

2. For patients without access to advanced imaging:

   • Non-contrast CT alone is insufficient to select wake-up stroke patients for tenecteplase treatment 1
   • Standard medical care without thrombolysis is currently recommended

Important Considerations and Caveats

• The TRACE-III trial (2024) showed benefit of tenecteplase in the 4.5-24 hour window in patients with large vessel occlusion and salvageable tissue on perfusion imaging, but this was in a Chinese population with limited access to thrombectomy 3
• In contrast, the TIMELESS trial (2024) found no benefit of tenecteplase in the 4.5-24 hour window in patients with large vessel occlusion and salvageable tissue, when most patients (77.3%) underwent thrombectomy 4
• These conflicting results suggest that tenecteplase may only provide benefit in extended time windows when thrombectomy is not available

Common Pitfalls to Avoid

• Do not administer tenecteplase based solely on non-contrast CT in wake-up stroke patients
• Do not assume that favorable perfusion on CT perfusion alone justifies tenecteplase use in wake-up stroke without considering other selection criteria
• Remember that the benefit of tenecteplase in wake-up stroke has not been clearly established, even with advanced imaging selection
• When using tenecteplase, the recommended dose is 0.25 mg/kg (maximum 25 mg) as a single IV bolus 5

In summary, while research continues in this area, current evidence does not support the routine use of tenecteplase in wake-up stroke patients selected by perfusion imaging alone. The most recent and highest quality evidence from the TWIST trial specifically addressing this question showed no benefit.