Tenecteplase at 4.5–24 hours without thrombectomy feasible for ischaemic stroke

The use of tenecteplase in the extended time window of 4.5–24 hours improves functional outcomes in patients with ischaemic stroke when endovascular thrombectomy (EVT) is not immediately available, findings from the phase III TRACE-III* trial suggest.

Tenecteplase is an effective thrombolytic agent for eligible stroke patients treated within 4.5 hours after stroke onset. However, data on the effect of late tenecteplase administration (after 4.5 hours after stroke onset) are lacking, the researchers said.

“In this trial involving Chinese patients with ischaemic stroke due to anterior-circulation large-vessel occlusion (LVO) who had salvageable tissue, most of whom did not undergo EVT, tenecteplase administered between 4.5 and 24 hours after patients were last known to be well was shown to improve disability-free recovery,” they continued.

A third of tenecteplase recipients had no disability (defined as Modified Rankin Scale [MRS] score 0 or 1) at 90 days (primary outcome). In the control arm, only 24.2 percent achieved this outcome (relative rate [RR], 1.37; p=0.03). [N Engl J Med 2024;391:203-212]

There were also more functionally independent (MRS score ≤2) participants at 90 days in the tenecteplase vs control arm (43.6 percent vs 33.3 percent; RR, 1.31).

Mortality at 90 days was similar between the experimental and control arms (13.3 percent vs 13.1 percent; RR, 1.01), but the incidence of symptomatic intracranial haemorrhage within 36 hours following treatment was higher in the former than the latter (3 percent vs 0.8 percent; RR, 3.82).

In this study, 516 participants (median age 67 years, 67.8 percent men) were randomized 1:1 to receive IV tenecteplase as a bolus administered over a period of 5–10 seconds (at a dose of 0.25 mg per kg; maximum dose 25 mg) or antiplatelet therapy at investigators’ discretion 4.5–24 hours after the time patients were last known to be well.

An exciting advance in stroke care

TRACE-III provides evidence that ischaemic stroke patients who have become ineligible for thrombectomy by the time they arrive at the thrombectomy centre may benefit from IV tenecteplase at the primary stroke centre. [N Engl J Med 2018;378:708-718] “This approach does require perfusion imaging capability at these smaller hospitals, but TRACE-III and other trials provide evidence for the feasibility of this approach with the use of CT-based methods and automated software,” the researchers noted.

“[However,] the use of tenecteplase in the extended time window in conjunction with a model of transfer to another facility for planned thrombectomy was not well represented in [TRACE-III] and continues to remain a gap in knowledge that warrants further trials,” noted Dr Vivien Lee from Ohio State University Wexner Medical Center, Columbus, Ohio, US, in a separate editorial. [N Engl J Med 2024;391:273-275]

Nonetheless, Lee underscored that the results “represent an exciting advance in acute stroke care. In patients with ischaemic stroke due to LVO who had salvageable penumbra and did not have access to thrombectomy … tenecteplase administered up to 24 hours after the time the patient was last known to be well was associated with higher incidences of a good functional outcome and revascularization than standard medical treatment.”

“The use of tenecteplase in an extended time window provides a new adjunctive treatment option in our armamentarium against the most devastating type of ischaemic stroke, and this has far-reaching global clinical implications,” Lee continued.

In areas lacking resources to develop thrombectomy programmes, tenecteplase administered in the 24-hour window following stroke onset may be a practical treatment alternative that could improve functional outcomes in patients with LVO on an international scale, she added.