May 5, 2023

• Acute ischemic stroke (AIS) is a time-dependent emergency; a disease spectrum that can broadly be divided into events affecting large vessel occlusion and everything else. This point of view is useful in the emergency department as it helps focus on urgent therapeutic approaches for two groups (6):

  • Patients eligible for mechanical thrombectomy.

  • Patients not eligible for mechanical thrombectomy.

• Early detection and appropriate management of AIS is critical for improving functional outcome and prevention of therapeutic-associated complications (eg. bleeding). 

• Fibrinolytics are high risk medications that are inherently associated with hemorrhage complications. Precise selection of patients and thorough review of absolute and relative contraindications is imperative: a neurologist should be involved to provide this therapy. 

IV alteplase recommendations (2)

Summary of recommendations on tenecteplase for AIS (7)

1. Tenecteplase at a dose of 0.25 mg/kg is equally safe and effective to alteplase for the treatment of patients presenting with stroke symptoms within 4.5 h.

2. Tenecteplase should not be used at a higher dose for stroke treatment.

3. Tenecteplase at a dose of 0.25 mg/kg may be better than alteplase for patients treated in a specialized ambulance capable of performing brain imaging.

4. Patients with stroke due to a blood clot in a large artery in the brain should be treated with tenecteplase at a dose of 0.25 mg/kg rather than alteplase, prior to receiving an intervention to remove the clot out of the body (thrombectomy).

5. For patients becoming aware of stroke symptoms on awakening from sleep or those presenting without information on the time of symptom onset, clot-busting medications can only be given if access to special brain imaging is available. In this setting we do not know whether tenecteplase can be used instead of alteplase. However, the opinion of the experts writing the current document is that tenecteplase at a dose of 0.25 mg/kg may be used instead of alteplase in patients becoming aware of stroke symptoms on awakening from sleep or those presenting without information on the time of symptom onset, provided they meet certain criteria on special brain imaging.

Webinar presentation of ESO Expedited Recommendation on Tenecteplase for Acute Ischaemic Stroke by S. Alamowitch. February 2, 2023. 

There is not a definite and universally accepted list of contraindications to fibrinolytic therapy, and there seems to be a tendency for it to become simpler over the years. Please be aware that references may differ on certain issues:

Absolute contraindications (1, 2, 3)

• Previous intracranial hemorrhage or stroke of unknown origin at any time

• Ischemic stroke in the preceding 6 months

• Central nervous system damage or neoplasms or arteriovenous malformation

• Recent major trauma / surgery / head injury (within the preceding month)

• Gastrointestinal bleeding within the past month

• Known bleeding disorder (excluding menses)

• Aortic dissection

• Non-compressible punctures in the past 24 hours (e.g. liver biopsy, lumbar puncture)

• Active internal bleeding

Relative contraindications (1, 2, 3)

• Transient ischemic attack in the preceding 6 months

• Oral anticoagulant therapy

• Pregnancy or within 1 week postpartum

• Refractory hypertension (SBP >180mmHg and/or DBP >110 mmHg)

• Advanced liver disease

• Infective endocarditis

• Active peptic ulcer

• Prolonged or traumatic resuscitation

• Alteplase

• Fibrinolytics summary table

• Tenecteplase

1. Ibanez B, James S, Agewall S, et al. 2017 ESC Guidelines for the management of acute myocardial infarction in patients presenting with ST-segment elevation: The Task Force for the management of acute myocardial infarction in patients presenting with ST-segment elevation of the European Society of Cardiology (ESC). Eur Heart J. 2018;39(2):119-177. doi:10.1093/eurheartj/ehx393.
   Pubmed

2. Powers WJ, Rabinstein AA, Ackerson T, et al. 2018 Guidelines for the Early Management of Patients With Acute Ischemic Stroke: A Guideline for Healthcare Professionals From the American Heart Association/American Stroke Association [published correction appears in Stroke. 2018 Mar;49(3):e138] [published correction appears in Stroke. 2018 Apr 18;:]. Stroke. 2018;49(3):e46-e110. doi:10.1161/STR.0000000000000158.
   Stroke (Open Access)

3. Konstantinides SV, Meyer G, Becattini C, et al. 2019 ESC Guidelines for the diagnosis and management of acute pulmonary embolism developed in collaboration with the European Respiratory Society (ERS). Eur Heart J. 2020;41(4):543-603. doi:10.1093/eurheartj/ehz405.
   Pubmed

4. Putaala J, Saver JL, Nour M, Kleindorfer D, McDermott M, Kaste M. Should Tenecteplase be Given in Clinical Practice for Acute Ischemic Stroke Thrombolysis?. Stroke. 2021;52(9):3075-3080. doi:10.1161/STROKEAHA.121.034244
   Stroke (Open Access)

5. Kvistad CE, Næss H, Helleberg BH, et al. Tenecteplase versus alteplase for the management of acute ischaemic stroke in Norway (NOR-TEST 2, part A): a phase 3, randomised, open-label, blinded endpoint, non-inferiority trial. Lancet Neurol. 2022;21(6):511-519. doi:10.1016/S1474-4422(22)00124-7
   Pubmed

6. Meschia JF. Diagnostic Evaluation of Stroke Etiology. Continuum (Minneap Minn). 2023;29(2):412-424. doi:10.1212/CON.0000000000001206
   Pubmed

7. Alamowitch S, Turc G, Palaiodimou L, et al. European Stroke Organisation (ESO) expedited recommendation on tenecteplase for acute ischaemic stroke. Eur Stroke J. 2023;8(1):8-54. doi:10.1177/23969873221150022
   Pubmed Central (Open Access)