When a patient displays the signs or symptoms of a stroke, time is of the essence and quick oxygen delivery to the brain is crucial. A new drug called tenecteplase (TNK) is supposed to be a faster and more effective treatment than the current standard, but medical professionals are speaking up about the drug’s potentially disastrous effects.
Last year, one nurse in the Emergency Department at Martha Jefferson Hospital instructed me to use caution if I ever had a patient or a family member eligible to be administered TNK, sharing that she has seen otherwise healthy patients who have bled out and died in gruesome ways after being treated with it. A few months later, another nurse at the UVA Medical Center told me that while working in a neurology and stroke unit, she was ordered by a doctor to administer TNK despite voicing her concerns. The next day, her patient died. They later found out that the patient had intracranial hemorrhage—bleeding in his brain—which is a clear contraindication of administering the drug. The bleeding may have been carelessly missed or perhaps did not show up on scans, but this patient should not have been given TNK, and people suffered because of it.
These nurses were so passionate about the dangers of TNK that it made me wonder how it is ethically being used in hospitals. After some research, I found that it is a newer version of a clot-busting drug that is thought to be faster, easier, and more effective at treating acute ischemic strokes than the previous standard called alteplase. Although many hospitals and health systems, like the Cleveland Clinic, are now transitioning to using TNK for stroke care, it still has not been approved by the FDA for this purpose [1]. It is still unclear why the company that creates TNK has not applied for FDA approval to use the drug to treat ischemic stroke (it is approved to treat heart attacks). Some doctors theorize that it is in an effort to keep the price down, as FDA approval would likely increase demand [2]. This drug seems to be reliable, yet it does not have the stamp of approval from the administration that ensures public health. Is TNK safe or is it putting lives at risk?
For patients with ischemic strokes, the recanalization of occluded blood vessels as early as possible is critical to preserving their function and quality of life. As a result, intravenous thrombolysis, or the breaking up of clots, has been recommended as the first-line therapy for ischemic stroke [3]. Because blood clots in the brain prevent it from receiving crucial oxygen, the sooner these thrombolytic treatments are given, the better chance a patient has at returning to their pre-stroke capabilities [4].
The only FDA-approved treatment for ischemic stroke is intravenous alteplase given within the first three hours after stroke symptoms start. This drug essentially breaks up clots that are blocking blood flow to the brain and stopping it from receiving oxygen [4]. However, alteplase must be given in two doses—the first as a quick single IV bolus, and the second as an IV infusion that takes at least an hour [1]. This clot-buster has been the standard for the past 30 years—until now.
TNK has the same clot-busting effect as alteplase, but it is modified with a higher attraction to blood clots. This means that TNK could result in less potentially life-threatening bleeding in other unintended parts of the brain [4]. In other words, TNK does a better job at breaking apart only what it needs to, with less collateral damage. Additionally, TNK can be effectively used within 4.5 hours of the patient’s last known well time [6]. TNK’s longer window of use allows more stroke patients to be treated, especially those who have passed the 3.5 hour mark and can no longer have alteplase. Furthermore, the administration of TNK is both faster and easier than alteplase, as it does not require an IV infusion. Instead, the medication is delivered in one dose through a syringe. It takes about five seconds to administer, meaning that it requires less nursing care and resources. This quality of TNK is critical—time is of the essence in ischemic stroke cases, and the faster a medication can be given, the better. Because of its ease, TNK can also be administered easily in pre-hospital settings, preventing the delay of life-saving care for those who live far from a hospital. Moreover, patients are not attached to an IV for an hour, meaning they can be easily transferred to a stroke center to receive a high level of care [5]. Lastly, both in the US and internationally, TNK is consistently less expensive than alteplase, costing about $6,000 per dose of TNK versus $9,000 per dose of alteplase [7].
There seem to be a lot of benefits to TNK—but is it effective? In a study of 6,864 patients with ischemic stroke, patients treated with TNK had a lower mortality rate (8.2%) than patients treated with alteplase (9.8%) at 30 days after thrombolysis. They also had a lower risk of major bleeding, measured by the frequency of blood transfusions (0.3% versus 1.4%) [8]. Additionally, Dr. Andrew Russman, the Head of Cleveland Clinic’s Stroke Program, discussed the EXTEND-IA TNK trial where “early reperfusion was achieved in 22% of patients who received TNK versus 10% of those who received alteplase” [6]. This means that TNK resulted in a greater percentage of patients who had early restored blood flow to their brain, which is critical to survival and quality of life after a stroke. However, according to a Canadian study that included around 1,600 patients, TNK and alteplase performed equally well “when comparing bleeding rate and dissolving the clot.” In fact, about 89-93% of patients in both groups had good or excellent outcomes, and only about 3.5% of patients in both groups had bleeding complications [5].
It seems to be an evolving conversation if TNK is actually more effective than alteplase at increasing positive outcomes and reducing complications from ischemic stroke. However, TNK has no additional negative side effects while being faster, less expensive, and easier to administer in situations where time matters. The fearful warnings that I received seem to be lacking in scientific basis.
With any thrombolytic medication or therapy, providers must use a lot of caution, and risk always exists. Patients might experience minor bleeding, intracranial or systematic hemorrhage, and immunologic complications. Despite this, for most patients, the advantages of quick treatment outweigh these rare complications [9]. As always, informed consent is of the utmost importance, and treatment decisions must be individualized.
While TNK usage for ischemic stroke has not yet been approved by the FDA, the National Institute of Neurological Disorders and Stroke and the American Heart Association both deem the medication effective and safe [1]. Although research is still continuing on its effectiveness, it is easy to see why many hospitals are transitioning to the use of TNK. As long as healthcare providers are using caution and providing in-depth care, this modern technology should be celebrated, not treated with fear.
References:
1. Why more hospitals are switching the medication used to stop a stroke. Henry Ford Health - Detroit. (2023, July 14). https://www.henryford.com/blog/2023/07/why-more hospitals-are-switching-the-medication-used-to-stop-a-stroke.
2. Fallik, D. (2023, June 15). IV tenecteplase results in fewer symptomatic intracranial hemorrhages than alteplase in patients with acute ischemic stroke. Neurology Today. https://journals.lww.com/neurotodayonline/blog/breakingnews/pages/post.aspx?PostID=1 368.
3. Li, G., Wang, C., Wang, S., Xiong, Y., & Zhao, X. (2022, May 11). Tenecteplase in ischemic stroke: Challenge and opportunity. Neuropsychiatric Disease and Treatment. https://www.dovepress.com/tenecteplase-in-ischemic-stroke-challenge-and-opportunity-p eer-reviewed-fulltext-article-NDT.
4. U.S. Department of Health and Human Services. (2023, May 26). Stroke Treatment. National Heart Lung and Blood Institute. https://www.nhlbi.nih.gov/health/stroke/treatment.
5. Girotra, T. (2022, December 28). Stroke drug tenecteplase dissolves clots as well as standard TPA-but in a single dose. UNM Health. https://unmhealth.org/stories/2022/12/stroke-drug-tenecteplase-dissolves-clots-as-well-as-standard-tpa-in-a-single-dose.html.
https://unmhealth.org/stories/2022/12/stroke-drug-tenecteplase-dissolves-clots-as-well-as -standard-tpa-in-a-single-dose.html.
6. Campbell, G. (2022, February 4). Making the switch from alteplase to tenecteplase for acute ischemic stroke. Cleveland Clinic. https://consultqd.clevelandclinic.org/making the-switch-from-alteplase-to-tenecteplase-for-acute-ischemic-stroke/.
7. Zachrison, K., & Schwamm, L. (2022, October 20). Making the case for tenecteplase as a treatment for acute ischemic stroke. Massachusetts General Hospital. https://www.mass general.org/news/research-spotlight/tenectepase-treatment-for-acute-stroke.
8. Murphy, L. et al. (2023, May 11). Tenecteplase versus alteplase for acute stroke: Mortality and bleeding complications. Annals of emergency medicine. https://pubmed.ncbi.nlm.nih.gov/37178103/.
9. Hengsterman, R. (2022, September 23). Thrombolytic therapy: TNKase or Activase? Nursing CE Central. https://nursingcecentral.com/thrombolytic-therapy/.