Acute Ischemic Stroke
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.
Tenecteplase 0.25 mg/kg is recommended over alteplase 0.9 mg/kg for large vessel occlusion AIS patients that are candidates to mechanical thrombectomy
For patients with acute ischaemic stroke of < 4.5 h duration and with large vessel occlusion who are candidates for mechanical thrombectomy and for whom intravenous thrombolysis is considered before thrombectomy, we suggest intravenous thrombolysis with tenecteplase 0.25 mg/kg over intravenous thrombolysis with alteplase 0.9 mg/kg (7).
Tenecteplase versus alteplase for AIS not eligible to mechanical thrombectomy
The recent European Guidelines from the European Stroke Organization recommend tenecteplase 0.25mg/kg IV as a valid first-line alternative to alteplase 0.9 mg/kg for AIS patients who are not eligible to mechanical thrombectomy (7). Also, recent guidelines from Australia, China and India similarly recognize tenecteplase as an appropriate first-line option for this indication (4).
The 2018 American Stroke Association recommendation about using tenecteplase 0.4mg/kg IV (2) has been questioned after the publication of the NOR-TEST 2 trial, in which was compared to alteplase 0.9mg/kg (standard treatment) for patients with AIS not eligible to thrombectomy (5).
The trial was prematurely terminated to fulfill the prespecified safety criteria.
Tenecteplase 0.4 mg/kg yielded worse safety and functional outcomes compared with alteplase.
Therefore, this practice guidance does not include the recommendation of AHA/ASA guidelines on this specific issue.
American Stroke Association
IV alteplase recommendations (2)
European Stroke Organization
Summary of recommendations on tenecteplase for AIS (7)
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.
Tenecteplase should not be used at a higher dose for stroke treatment.
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.
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).
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.
⚠ Contraindications to fibrinolytic therapy
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)
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
Active peptic ulcer
Prolonged or traumatic resuscitation
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.
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)
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.
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)
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
Meschia JF. Diagnostic Evaluation of Stroke Etiology. Continuum (Minneap Minn). 2023;29(2):412-424. doi:10.1212/CON.0000000000001206
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)
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