Tenecteplase Demonstrates Better Efficacy Outcomes Than Alteplase in Telestroke

In addition to significantly less disability observed in tenecteplase-treated patients, this group was also administered treatment 9.40 minutes faster than those on alteplase.

Although alteplase is the standard thrombolytic treatment for acute ischemic stroke (AIS), new findings suggest that tenecteplase, a genetically engineered version of alteplase, leads to better 90-day outcomes without increased complication rates for telestroke patients with large vessel occlusion (LVO).

Using modified Rankin Scale (mRS) score ordinal shift analysis, senior author Ashis Tayal, MD, neurologist, Wellstar Health System, and colleagues found significantly less disability in tenecteplase-treated patients at 90 days compared with those on alteplase (adjusted odds ratio [aOR], 0.31; 95% CI, 0.14-0.72; P = .006). The findings, presented at the 2022 American Academy of Neurology (AAN) Annual Meeting, April 2-7, in Seattle, Washington, add to the limited collection of data concerning tenecteplase use for telestroke patients.

In this retrospective analysis, outcomes for telestroke patients treated with intravenous (IV) alteplase from May 2018 to April 2020 were compared with patients treated with IV tenecteplase from May 2020 to April 2021. There were 3747 telestroke consults during the study and 537 (14.3%) were found to have an LVO, of which 109 (tenecteplase: n = 39; alteplase: n = 70) were eligible.

Although tenecteplase led to better functional outcomes, the 2 groups were similar in terms of complication rates (aOR, 3.73; 95% CI, 0.23-59.95; P = .35). Notably, using an adjusted quantile regression model instead of ordinal regression or binominal logistic regression, investigators found that tenecteplase was administered 9.40 minutes quicker than alteplase (SE, 3.67; 95% CI, 2.11-16.69; P = .01). Door-in door-out time (DIO), a secondary outcome, was not different between treatment arms (P = .63).

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There have been several reports that have shown tenecteplase to be noninferior, or even superior, to alteplase; however, this is one of the few studies to observe it with telestroke. Stroke telemedicine operates on a distinct site-and-originating site system that comprises of a large team, including a program management, clinical coordinator, vascular neurologists, neurosurgeons and radiologists at the distant site, and emergency medicine doctors and other staff at the originating site.

Tenecteplase is a tissue plasminogen activator (tPA) developed from modifications of natural human tPA complementary DNA. It binds to fibrin-rich clots and cleaves the Arg/Val bond in plasminogen to form plasmin, which then degrades the fibrin matrix of the thrombus, thereby exerting its thrombolytic action. One notable phase 3 study, TIMELESS (NCT03785678), is currently ongoing and aims to confirm tenecteplase’s benefit over alteplase in patients with AIS.

Alteplase, an IV-administered medication, has practical issues that have forced clinicians to explore the use of tenecteplase in the acute setting. Thus far, research has suggested that tenecteplase is as efficacious as alteplase with regard to neurologic improvement, and its theoretical advanced including greater fibrin specificity and longer half-life.2

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REFERENCES
1. Hackett C, Malholtra K, Cerejo R, et al. Tenecteplase is safe and efficacious in telestroke patients with confirmed large vessel occlusions. Presented at: 2022 AAN Annual Meeting; April 2-7; Seattle, Washington. Abstract 1588
2. Tanswell P, Modi N, Combs D, Danays T. Pharmacokinetics and pharmacodynamics of tenecteplase in fibrinolytic therapy of acute myocardial infarction. Clin Pharmacokinet. 2002;41(15):1229-1245. doi:10.2165/00003088-20041150-00001