BARCELONA, Spain — A new individual patient-level meta-analysis confirms that the newer bolus thrombolytic, tenecteplase, is noninferior to alteplase for acute ischemic stroke — and may even offer superior outcomes.

Study investigator, Keith Muir, MD,consultant neurologist, University of Glasgow, Glasgow, Scotland, explained that several individual trials have suggested noninferiority of tenecteplase to alteplase, but they have had fairly wide margins for defining noninferiority because of limited statistical power.

The latest data from the meta-analysis of individual patients in the trials have confirmed noninferiority not only for the 3% boundary but also for the more rigorous 1.3% boundary in terms of the favorable functional endpoint of modified Rankin scale (mRS) scores of 0-1 at 90 days.

The meta-analysis is not complete at present because individual patient data are still awaited for three of the 12 trials included. But if study-level data from these three trials are added, then the superiority of tenecteplase over alteplase is shown, Muir noted.

“Putting it altogether, this data gives us reassurance that tenecteplase is the thrombolytic of choice for treatment of acute ischemic stroke in patients presenting within the 4.5 window,” Muir told Medscape Medical News.

“It is very encouraging to see that we have clearly got noninferiority and probable superiority at very low hemorrhage rates with a very good safety profile,” he added.

The interim CATALYST-TNK study was presented on October 22 at the 17th World Stroke Congress (WSC) 2025.

Ease of Use Advantage

Muir explained that large differences between the two drugs are not expected as they are very similar, but tenecteplase has the advantage of being much easier to use.

“Alteplase is a very effective drug, so it is unlikely that tenecteplase will be much more beneficial in terms of outcomes. But just knowing that tenecteplase is noninferior is sufficient to make it the drug of choice for use in acute ischemic stroke because it is so much more convenient to use, with its bolus dose administration,” he noted.

“Alteplase, which is given by a bolus followed an hour’s infusion, is difficult to give in the emergency situation where we are moving patients around and transferring between hospitals. It is quite impractical and challenging to deliver reliably in that environment,” Muir added.

There have been hints that tenecteplase may be slightly more effective than alteplase previously, but this individual patient meta-analysis is going to be able to refine that observation, and more accurately establish the noninferiority boundaries, Muir noted.

The new meta-analysis will eventually include data of about 7500 patients from 12 trials comparing tenecteplase (at the 0.25-mg/kg dose) with alteplase in patients with acute ischemic stroke presenting within 4.5 hours of symptom onset.

The interim analysis includes data of 4500 patients across nine trials, along with study-level results from three additional trials — TRACE-1, TRACE-2, and ACT — pending individual patient data.

So far, analysis of the available data shows the primary favorable outcome (mRS 0-1) occurred in 53.7% of alteplase patients and 56.0% of tenecteplase patients, giving an absolute difference of 2.3% in favor of tenecteplase. This is within the noninferiority margins at both -3% and -1.3% thresholds (P < .001). But superiority is not significant.

However, if study-level data from the three remaining trials are added in, results show that 50.7% of alteplase patients achieved the mRS 0-1 outcome vs 53.2% of tenecteplase patients, an absolute difference of 2.5% in favor of tenecteplase. This meets both noninferiority margins and fulfills superiority criteria — relative risk, 1.049 (95% CI, 1.011-1.089; P = .016), Muir reported.

In terms of safety, the point estimate for symptomatic hemorrhage is trending slightly toward a higher risk with tenecteplase (2.6% vs 2.2%), but Muir pointed out that this is nonsignificant, with very wide CIs.

Fatal hemorrhages in the first 7 days were the same in both groups at about 1%, and the mortality rates were also very similar (8.7% in tenecteplase vs 8.8% in alteplase).

“I would not over interpret these nonsignificant hemorrhage results as they’re based on very small numbers of events,” Muir said.

More accurate results on both efficacy and safety will be reported when all the individual patient data from the remaining trials become available, which should be “very soon,” said Muir.

This will also allow adjustment for baseline prognostic markers and examination of whether there are any differences between subgroups, he added.

Global Shift Toward Tenecteplase

Muir noted that a recent shortage of tenecteplase has now been resolved. The shortage occurred because both alteplase and tenecteplase were manufactured at a single facility, and a global surge in demand for alteplase several years ago temporarily diverted production away from tenecteplase.

Boehringer Ingelheim, the primary manufacturer for most of the global market, has since opened a second plant dedicated specifically to tenecteplase production.

Muir noted the recent licensing of tenecteplase for stroke helped justify this investment. “There is definitely a global shift toward tenecteplase for stroke treatment now, and the data from this meta-analysis support that move,” he said.

Commenting on the results of the CATALYST-TNK meta-analysis, Bastian Cheng, MD, stroke neurologist at the University Medical Center Hamburg-Eppendorf, Hamburg, Germany, said the noninferiority results were clear but whether tenecteplase was superior to alteplase is not yet confirmed.

“We are looking forward to seeing the final results of this meta-analysis when all the individual patient data are available to see if superiority can be shown,” he added.

The CATALYST-TNK meta-analysis is supported by a grant from Boehringer Ingelheim to the University of Glasgow. Muir reported serving as a consultant for and receiving grant support from Boehringer Ingelheim.