Benefits of Switching to Tenecteplase for Stroke Thrombolysis

February 28, 2020

Switching from alteplase to tenecteplase as the thrombolytic used routinely for acute ischemic stroke is having multiple benefits for one US hospital system.

Tenecteplase was developed as a more fibrin-specific thrombolytic than alteplase with the advantage of being administered as a bolus dose rather than a bolus and a 60-minute infusion as is the case for alteplase.  

Both agents are manufactured by the same companies (Genentech/Boehringer Ingelheim), which have not sought approval for use of tenecteplase in stroke, but in recent years, academic investigators have conducted several studies suggesting possible benefits of tenecteplase over alteplase.

Tenecteplase is used quite frequently in Australia, New Zealand, and Norway, where the studies have mainly been conducted, and now several hospitals in the United States are also starting to favor the newer bolus thrombolytic.

The experience of one of these US healthcare systems was described by Steven J. Warach, MD, professor of neurology at the University of Texas at Austin, in a presentation at the recent International Stroke Conference (ISC) in Los Angeles.

"We have switched to routine use of tenecteplase for all stroke thrombolysis in our group of 9 hospitals," Warach told Medscape Medical News.  

"We did this after scrutinizing the available data which we thought showed substantial and strong evidence for non-inferiority of tenecteplase with alteplase, with the suggestion that tenecteplase may have an advantage in leading to earlier recanalization."

But the main motivation for the switch is that tenecteplase saves time, he said. "It can be given as a single bolus dose whereas alteplase is given as a bolus followed by a 60-minute infusion. Sometimes there may be a gap between the alteplase bolus and the infusion which may lead to some of the benefit being lost," he explained.

The bolus administration of tenecteplase is especially useful for patients being transferred from smaller hospitals to the comprehensive stroke center for thrombectomy, Warach noted.

"The transport company is reluctant to take patients while on an alteplase drip. They want a nurse to be in the ambulance but the emergency department often can't spare a nurse to do that, so the patient has to wait for the alteplase to be finished," he noted. "That can cause a long delay."

Warach reported results of an observational cohort of the first 50 patients treated with tenecteplase after the switch was made in September 2019 with comparison to experience with alteplase in 327 patients over the previous 2 years.

"We found that we are saving about half an hour by using tenecteplase instead of alteplase. That is a significant time saving and could lead to meaningful improvements in outcomes," he said. 

Another advantage of using tenecteplase is cost, as the bolus agent is cheaper. "The price differential between one dose of alteplase and one dose of tenecteplase in our hospital is $3,098. That is a large cost saving over the year," Warach commented.

In the cohort study, dosing errors occurred in 8% of patients receiving alteplase (3% had a delay to the infusion after the bolus and 5% had the infusion interrupted), whereas there was one dosing error with tenecteplase when the dose used for ST-segment elevation myocardial infarction (MI), 0.5 mg/kg, was given.

Door-to-needle time was 57 minutes for alteplase and 50 minutes for tenecteplase, with 28% of alteplase patients receiving treatment within 45 minutes versus 40% of tenecteplase patients.

For patients receiving thrombectomy, the median time from bolus thrombolytic to start of the thrombectomy procedure was 124 minutes in the alteplase patients versus 105 minutes in those given tenecteplase.

"The time difference is reinforced when we look at transfer times from primary stroke centers to comprehensive stroke centers," Warach stated.

As tenecteplase is more fibrin-specific than alteplase, it has the potential to cause less bleeding, Warach noted. "In trials in MI patients, there was a reduction in major bleeding throughout the body with tenecteplase versus alteplase. In stroke studies so far we can say it is definitely not worse in terms of bleeding and there is a trend towards tenecteplase causing less bleeding and intracranial hemorrhage," he added.

In the Austin cohort study, symptomatic intracranial hemorrhage occurred in 2.4% of alteplase patients versus 0% of tenecteplase patients.

Discharge status showed that 43% of alteplase patients and 52% of tenecteplase patients were discharged home, and 45% of alteplase patients versus 52% of those given tenecteplase had independent ambulation.

Warach cautioned that these results should be interpreted with several limitations in mind.

"The alteplase and tenecteplase samples are not contemporaneous, so improvements in workflow times might be attributable to other ongoing process improvement efforts, and 50 subjects is a small sample and statistical testing was neither planned or attempted, rather descriptive comparisons were performed," he noted.

The investigators are continuing to collect data on further patients treated with tenecteplase to increase the size of the registry.

Warach noted that his hospital system is one of the first in the United States to switch to tenecteplase as the standard of care thrombolytic for use in stroke. "There are a few other hospital systems doing it now I think. We have had a lot of interest in what we are doing and in the ISC presentation of our data," he said.  

He stressed that the transition was implemented cautiously. "There is always some reluctance in being one of the early adopters of a new treatment strategy. We went about it very methodically, and made sure all the departments involved had access to the data available on tenecteplase themselves and everyone was in agreement."  

The workflow in the emergency department has benefited considerably for the change, he added. "They are very happy not to have to set up an alteplase infusion anymore."

There has been some uncertainty on the optimum dose of tenecteplase in stroke, and Warach and his team chose the 0.25-mg/kg dose. "We were very glad to see the new data at ISC from the Australian EXTEND-IA group validating that this appears to be the best dose," he added.

Commenting on the presentation for Medscape Medical News, Jeremy Payne, MD, medical director of the stroke program at Banner University Medical Center, Phoenix, Arizona, said that although the Austin study was small so far and observational, it nonetheless filled an important role.

"We've been following tenecteplase for quite some time as it has several potential advantages over alteplase but the data available in stroke have been somewhat heterogeneous in regards to both dose and types of patients treated and there has not been enough for a level 1 indication, so it is great to see some unconstrained data from a real world setting," he said. 

"I think the Austin data look great and back up what previous studies have suggested — that tenecteplase looks comparable or even better than alteplase, with obvious advantages for patients needing to be transported to a larger center for endovascular therapy," he added.

Warach reports that he is chair of the data safety monitoring committee of the ongoing Genentech-sponsored TIMELESS trial of tenecteplase in acute ischemic stroke. Payne reports no relevant financial relationships.

International Stroke Conference (ISC) 2020: Abstract LB10. Presented February 20, 2020.

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