Safely Expanding the Time Window of Thrombolysis: Gregory W. Albers, MD

Commentary
Video

The professor of neurology and director of the Stanford Stroke Center discussed the ways stroke care is evolving and the significance of the TIMELESS trial, which demonstrated the safety of tenecteplase in later-window poststroke patients. [WATCH TIME: 7 minutes]

WATCH TIME: 7 minutes

"We’ve been at least able to say, here’s a subgroup of patients who can be treated safely. The downside of course, was that the primary outcome of efficacy was not statistically significant. It’s hard to make the argument to treat them if we don’t have strong efficacy. Part of the problem with the way our study turned out was that there was a very short time for the drug to do its thing and dissolve the clot."

Intravenous thrombolytic therapy with alteplase has generally been the standard care for eligible patients within 4.5 hours after the onset of ischemic stroke. One limitation for extending the time window for thrombolysis has been an increase in the incidence of intracranial hemorrhage. TIMELESS, a multicenter, placebo-controlled trial, tested the hypothesis that intravenous tenecteplase, initiated 4.5 to 24 hours after stroke onset, would provide a benefit in patients who had a large-vessel occlusion of the internal carotid artery or the first (M1) or second (M2) segments of the middle cerebral artery and had evidence of salvageable ischemic brain tissue identified on CT perfusion or MRI perfusion.

Led by Gregory W. Albers, MD, the trial featured 458 enrolled patients with ischemic stroke, most of which (77.3%) subsequently underwent thrombectomy prior to receiving either tenecteplase (n = 228) or placebo (n = 230). At 90 days, the 2 groups showed no significant differences in modified Rankin Scale (mRS) scores (adjusted OR, 1.13; 95% CI, 0.82-1.57; P = .45; favoring tenecteplase), the primary end point, with similar incidence rates of intracerebral hemorrhage (tenecteplase: 3.2% vs placebo: 2.3%). In addition, the incidence of recanalization at 24 hours appeared to be higher with tenecteplase, but the incidence of reperfusion was similar in the 2 groups at the end of the procedure.

All told, the study highlighted the fact that tenecteplase can be safely administered in late-window patients with ischemic stroke. Albers, a professor of neurology and director of the Stanford Stroke Center, recently sat down with NeurologyLive® to discuss the expansion of endovascular therapy and the previous studies before TIMELESS. He spoke on the subgroups of patients from the study that benefitted more from Tenecteplase, and the need to further confirm these findings in large-scale studies. Additionally, he discussed the complexities with conducting trials in this patient population and whether outcomes vary based on the time tenecteplase is given following thrombectomy.

REFERENCE
1. Albers GW, Jumaa M, Purdon B, et al. Tenecteplase for stroke at 4.5 to 24 hours with perfusion-imaging selection. NEJM. Published February 8, 2024. doi:10.1056/NEJMoa2310392
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