Tenecteplase May Improve Stroke Recovery After 4.5-Hour Treatment Window

 NOT GOOD ENOUGH! Where are the follow-on 100% recovery protocols? Oh, you incompetently are ignoring survivor requirements! Comeuppance is going to be a bitch when you are the 1 in 4 per WHO that has a stroke? Then you just might want 100% recovery.

Tenecteplase May Improve Stroke Recovery After 4.5-Hour Treatment Window

Treatment with the clot-busting drug tenecteplase given between 4.5 and 24 hours after stroke onset improved functional outcomes compared with standard therapy, according to a new study.

The multicenter, randomized clinical trial included 566 patients in China with acute ischemic stroke without large vessel occlusion and with potentially salvageable brain tissue determined by advanced imaging. About half of the participants received intravenous tenecteplase, and half were treated with standard antiplatelet therapy 4.5 to 24 hours after symptoms appeared.

Ninety days after treatment, 43.6% of participants who received tenecteplase showed excellent function compared with 34.2% of those treated with antiplatelet therapy. However, the tenecteplase group also experienced a slightly increased risk for brain bleeding. The results were published online on February 5 in JAMA.

Extending the Time Window

The American Heart Association’s “2026 Guideline for the Early Management of Patients with Acute Ischemic Stroke” recommends intravenous thrombolysis with tenecteplase or alteplase, a similar drug, for acute ischemic stroke. Dual antiplatelet therapy is recommended for those with minor symptoms to reduce the risk for bleeding. Either treatment should be administered within 4.5 hours (or within 9 hours for thrombolysis if imaging indicates) of symptoms to ensure the best outcomes.

A 2025 meta-analysis of eight randomized trials suggested that intravenous thrombolysis after 4.5 hours still helped patients achieve excellent function(That's not 100% recovery, is it? So, you're still failing at stroke rehab, aren't you?). The TRACE III and HOPE trials looked at the possibility of extending the treatment window in patients with large-vessel occlusions who would receive thrombectomy as standard treatment, yet stroke due to clots in small and medium vessels is more common.

The authors found, “Endovascular thrombectomy has generally not been shown to benefit these patients. Evidence remains scarce from direct comparisons of intravenous thrombolysis vs standard medical treatment for acute ischemic stroke due to non-large vessel occlusion beyond 4.5 hours after onset.”

Previous studies have shown that tenecteplase is as effective as alteplase in people with acute ischemic stroke.

“There’s a lot of confidence that tenecteplase is better and easier to administer,” said Shyam Prabhakaran, MD, MS, the James Nelson and Anna Louise Raymond Professor of Neurology and chair of the Department of Neurology at UChicago Medicine, Chicago. Prabhakaran was not involved in the study.

Better Functional Outcomes

The new study reports the results of the OPTION trial, conducted from June 2023 to October 2025 at 48 centers in China.

Patients with acute ischemic stroke were recruited if they had a prestroke score of 0 or 1 on the modified Rankin Scale, indicating no symptoms or no significant disability despite symptoms; had moderate to severe poststroke symptoms according to the National Institutes of Health Stroke Scale; and had salvageable brain tissue based on imaging of the brain’s core volume and penumbra. Patients were excluded if they showed blood clots in the brain’s large arteries.

Of the final cohort of 566 patients, 282 (median age, 69 years; 62.4% men) received 0.25 mg/kg of intravenous tenecteplase, with a maximum dose of 25 mg/kg. The remaining 284 (median age, 67 years; 68.3% men) received antiplatelet therapy.

In the tenecteplase group, 43.6% of patients had an excellent functional outcome — defined as a modified Rankin Scale score of 0 or 1 at 90 days, assessed by phone interview — compared with 34.2% in the antiplatelet group. The results indicated an unadjusted risk difference of 9.46% (95% CI, 1.47-17.46) and an unadjusted risk ratio of 1.28 (95% CI, 1.04-1.57).

Approximately 3% of patients receiving tenecteplase experienced brain bleeding 36 hours after treatment compared with none of the antiplatelet group (risk difference 2.85%; P = .004). At 90 days, 14 patients (5.0%) in the tenecteplase group and nine (3.2%) in the control group had died (risk ratio, 1.57; 95% CI, 0.69-3.57; P = .28). 

Benefit Despite Bleeding Risk

The results support extending the time window for administering thrombolysis in this patient population, the authors wrote, even with the increased risk for symptomatic intracranial hemorrhage.

“Bleeding is an expected risk with tenecteplase; even if administered within 4.5 hours, those that receive thrombolytics do have greater risk of bleeding,” Prabhakaran told Medscape Medical News. “It doesn’t surprise me that the rate of hemorrhage is higher in the tenecteplase group, but the use of tenecteplase, despite the risk of bleeding, does increase the functional outcome.”

Prabhakaran noted that the study examined only Chinese patients, and the majority were men. Most participants had mild strokes but a relatively large amount of tissue at risk, which may represent a narrow subset of stroke patients.

“The study is answering an important question: if you have salvageable tissue — this population was chosen because they had very small core volume and a lot of salvageable tissue — tenecteplase was really a game changer,” Prabhakaran said. “This says we can use imaging up to 24 hours [after symptom onset] to potentially open up treatment to a larger number of people.”

The study was funded by the Beijing Hospitals Authority Clinical Medicine Development of Special Funding Support and the China Shijiazhuang Pharmaceutical Company Recomgen Pharmaceutical (Guangzhou) Co., Ltd. Neither funder had a role in the design or conduct of the study.

Kat Long is a science journalist in the Washington, DC area.