Acute Ischemic Stroke Management

Patient Selection and Treatment Timing

The American Heart Association recommends administering tenecteplase within 4.5 hours of stroke symptom onset in patients with acute ischemic stroke, with a Class I, Level of Evidence A recommendation for administration within 3 hours of symptom onset, and a benefit-to-risk ratio that is strongly time-dependent 1
Patients eligible for tenecteplase should be ≤80 years of age, without a history of both diabetes mellitus and prior stroke, with an NIHSS score ≤25, and no imaging evidence of ischemic injury involving more than one-third of the MCA territory, and should not have recent history of major surgery, trauma, or bleeding, or be taking oral anticoagulants or have an INR <1.7 if taking warfarin 1, 2
Patients with unknown symptom onset ("wake-up strokes") and a DWI/FLAIR mismatch on MRI may benefit from thrombolysis with tenecteplase, according to the American Heart Association/American Stroke Association (AHA/ASA) guidelines with a Class IIb, Level of Evidence B-R recommendation 3, 4

The recommended dose of tenecteplase is 0.25 mg/kg, maximum 25 mg, as a single IV bolus, which offers a better safety profile with comparable efficacy to alteplase, and is especially beneficial for patients requiring urgent transport to comprehensive stroke centers, patients eligible for mechanical thrombectomy, and patients with large vessel occlusion 1, 5, 6, 3
Door-to-needle time goals should be established with a primary goal of achieving treatment within 60 minutes in ≥50% of patients, and a secondary goal of door-to-needle times within 45 minutes in ≥50% of patients may be reasonable, with multicomponent quality improvement initiatives recommended to safely increase thrombolytic treatment rates 1
The American College of Cardiology and the American Heart Association list absolute contraindications for tenecteplase, including prior intracranial hemorrhage, known structural cerebral vascular lesion, known malignant intracranial neoplasm, ischemic stroke within 3 months, suspected aortic dissection, active bleeding or bleeding diathesis, significant closed-head or facial trauma within 3 months, intracranial or intraspinal surgery within 2 months, and severe uncontrolled hypertension (SBP >180 mm Hg or DBP >110 mm Hg) 7, 6

Tenecteplase has been shown to be non-inferior to alteplase in functional outcomes at 90 days in patients treated within 4.5 hours, with a higher rate of significant neurological improvement at 24 hours, and lower rates of symptomatic intracranial hemorrhage and major bleeding compared to alteplase 3, 1, 4
The EXTEND-IA TNK study demonstrated the superiority of tenecteplase over alteplase in arterial recanalization when administered before mechanical thrombectomy, with 22% vs 10% substantial reperfusion 3, 4
Tenecteplase is preferred over alteplase due to its higher specificity for fibrin, longer half-life, single-bolus administration, and better safety profile with comparable efficacy, according to the American Heart Association/American Stroke Association (AHA/ASA) guidelines with a Class IIb, Level B-R recommendation 3, 1, 6

The American Heart Association/American Stroke Association recommends tenecteplase as an alternative to alteplase in patients with minor neurological deterioration and no significant intracranial occlusion (Class IIb, Level B-R) 3, 1, 4
The American College of Emergency Physicians recommends thrombolysis within 3 hours of symptom onset (Level A recommendation) and suggests thrombolysis between 3-4.5 hours after symptom onset (Level B recommendation) 8, 9
Several ongoing trials, including TASTE, TEMPO-2, TWIST, and ATTEST-2, are examining tenecteplase's efficacy and safety, and the MOST trial has been adapted to include tenecteplase as standard-of-care thrombolytic therapy, reflecting its increasing adoption 4, 10