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Tenecteplase (TNK) for treatment of Acute Ischemic Stroke

After 25 years of Alteplase® (recombinant tissue plasminogen activator or r-tPA) being the only option for acute stroke thrombolysis, Tenecteplase® (TNK) is gaining traction as an alternative, and possibly better lytic. TNK has been FDA approved for acute MI since 2000 and is also used off label for pulmonary embolism in many centers. TNK is a bioengineered variant of naturally occurring tPA, an endogenous enzyme that promotes the breakdown of blood clots. Molecular changes to TNK make it more specific to fibrin and less prone to degradation by other naturally occurring enzymes. Greater fibrin specificity may mean fewer bleeding complications and resistance to degradation may mean better clot lysis. TNK has identical inclusion and exclusion criteria as tPA when used for acute ischemic stroke. TNK has the same potential complications of rtPA, including bleeding and angioedema and these complications are managed in the same way as r-tPA. There have been 3 major trials published in the last few years that have accelerated interest in using TNK for stroke, including NOR-TEST (Lancet Neurology. 2017;16:781-788), EXTEND-IA (NEJM. 2018;378:1573-82) and EXTEND-IA Part 2 (JAMA. 2020;323:1257-1265). A meta-analysis of 5 randomized trial comparing TNK and r-tPA a trend toward better efficacy an no signal of increased bleeding complications with TNK (Stroke. 2019;50:2156–2162) These publications led to support for TNK as an alternative to r-tPA in the 2019 American Heart Association/American Stroke Association Guidelines (Stroke. 2019;50:e344-e418). This has led to many hospitals across the country making the switch from r-tPA to TNK as their lytic of choice for stroke care, despite the drug still not having FDA approval. One of the major reasons for making the switch is that TNK can be administered as a single, rapid bolus as opposed to the bolus followed by hour-long infusion of r-tPA. This is particularly important in the clinical situation where a patient who is eligible for both thrombolysis and has a large vessel occlusion arrives to a hospital that does not perform cerebral thrombectomy. These patient need not only to be treated expeditiously with lytics, but then transferred to a center where thrombectomy can be performed. Maine EMS rules do not allow transport of patients with thrombolytic infusion running without an accompanying nurse with the PIFT paramedic. If appropriate personnel is not available, patients have to wait for the infusion of r-tPA to complete before transfer, which could worsen overall stroke outcome. Maine Medical Center switched to TNK on March 1, 2021 as the only thrombolytic used for acute ischemic stroke. Shortly after that several other MaineHealth hospitals also made the switch, including PenBay Medical Center, Waldo County General Hospital, Lincoln-Health Miles, MidCoast and Southern Maine Health Care. Other hospitals in the state are considering the switch as well.


About the Author:

Dr. Jane Morris is a neurohospitalist and stroke specialist working solely in the inpatient setting at Maine Medical Center in Portland, Maine. She trained in internal medicine and neurology and has an interest in the areas where medicine and neurology intersect. She has special interest in stroke in young patients, including working with cardiology to develop consistent and comprehensive approaches to strokes due to patent foramen ovales (PFO). She is interested in improving systems of care for all stroke patients across Maine and helped to establish the MaineHealth Telestroke Network.

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