Intravenous Tenecteplase Improves Functional Outcomes in Extended-Window Non-LVO Stroke
Key Clinical Summary
- In a randomized clinical trial of 566 patients with acute non–large vessel occlusion (non-LVO) ischemic stroke and salvageable brain tissue, intravenous tenecteplase given 4.5–24 hours after onset increased excellent functional outcomes (mRS 0–1 at 90 days) compared with standard medical treatment.
- Tenecteplase also improved early reperfusion and early clinical response at 24 hours but was associated with a higher rate of symptomatic intracranial hemorrhage within 36 hours.
- Mortality at 90 days did not differ significantly between groups.
The OPTION randomized clinical trial investigated whether intravenous tenecteplase administered in an extended time window (4.5–24 hours) after ischemic stroke onset benefits patients with non-large vessel occlusion (non-LVO) and evidence of salvageable brain tissue. Researchers observed a “greater likelihood of an excellent functional outcome at 90 days than standard care,” but this was accompanied by increased risk of symptomatic intracranial hemorrhage.
Published in JAMA, the findings provide evidence for thrombolytic use beyond conventional timeframes in a specific stroke subgroup.
Study Findings
The randomized, open-label, blinded end-point clinical trial enrolled 566 patients across 48 centers in China between June 2023 and August 2025. Eligible participants had acute ischemic stroke due to non-LVO with perfusion imaging showing potentially salvageable brain tissue and presented within 4.5 to 24 hours after last known well. Patients were randomized to receive intravenous tenecteplase (0.25 mg/kg; max 25 mg; n = 282) or standard medical treatment (n = 284).
The primary efficacy outcome was an excellent functional result, defined as a modified Rankin Scale (mRS) score of 0–1 at 90 days. This outcome was achieved in 43.6% of tenecteplase patients versus 34.2% with standard care (risk ratio [RR], 1.28; 95% CI, 1.04–1.57; P = .02). Secondary measures showed better overall mRS distribution and increased reperfusion at 24 hours with tenecteplase.
Safety outcomes, however, revealed a higher rate of symptomatic intracranial hemorrhage within 36 hours in the tenecteplase arm (2.8% vs 0; risk difference, 2.85% [95% CI, 1.16%-5.54%]; P = .004). Mortality at 90 days was 5.0% vs 3.2% (RR, 1.57; 95% CI, 0.69–3.57; P = .28).
Clinical Implications
This trial expands evidence on tenecteplase use in ischemic stroke beyond the traditional 4.5-hour thrombolytic window, specifically for patients with non-LVO strokes and salvageable cerebral tissue on perfusion imaging. The statistically significant improvement in excellent functional outcomes suggests an extended treatment window may be justifiable in carefully selected patients, supporting individualized decision-making guided by advanced imaging.
Clinicians should weigh the benefit of improved functional independence against the increased risk of symptomatic hemorrhage. The absolute increase in excellent outcomes underscores potential gains in independence and quality of life but highlights the necessity for vigilant monitoring after thrombolysis. These results may prompt revision of protocols for extended-window thrombolytic therapy in non-LVO stroke populations where endovascular thrombectomy is not indicated. The mortality findings, showing no significant difference at 90 days, reinforce the safety profile’s acceptability when balanced with efficacy.
Expert Commentary
“Among patients with non–large vessel occlusion acute ischemic stroke and salvageable brain tissue, tenecteplase administered 4.5 to 24 hours after onset resulted in a greater likelihood of an excellent functional outcome at 90 days than standard care but had an increased risk of symptomatic intracranial hemorrhage,” said Gaoting Ma, MD, Department of Neurology, Xuanwu Hospital Capital Medical University, National Center for Neurological Disorders, Beijing, China, and co-authors. They emphasize careful patient selection using perfusion imaging when considering late-window thrombolytic therapy.
Conclusion
Extended-window intravenous tenecteplase improves functional outcomes in selected non-LVO ischemic stroke patients with salvageable brain tissue, though with higher early hemorrhage risk. These findings may inform evolving stroke care protocols and imaging-guided treatment strategies.
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