乌鸦传媒

The TESLA trial was unable to support a benefit to thrombectomy for stroke patients with large-core infarcts identified on noncontrast CT within 24 hours.

Unlike other studies, endovascular therapy in TESLA conferred no significantly better improvement in 90-day functional outcome based on the mean utility-weighted modified Rankin Scale (mRS). With a score of 0 indicating death or severe disability and 10 zero symptoms on this scale, treatment and control arms of the trial scored a mean 2.93 versus 2.27, respectively (adjusted difference of 0.63, 95% credible interval -0.09 to 1.34).

"But the width of the credible interval around the effect estimate includes the possibility of both no important effect and a clinically relevant benefit, so the potential role of thrombectomy with this imaging approach and time window will likely require additional study," stated Osama Zaidat, MD, MS, of St. Vincent Medical Center-Bon Secours Mercy Health Medical Center in Toledo, Ohio, and colleagues in .

The investigators highlighted the relatively long median 11.5 hours from stroke onset to randomization in TESLA. This, they suggested, is one way it stands apart from the more positive studies on endovascular thrombectomy for large-core strokes, like the ANGEL-ASPECT (sub-8 hours) and SELECT2 trial (sub-10 hours) from last year, and the more recent that capped patient eligibility outright after 11 hours.

Also notable was TESLA's lack of advanced stroke imaging criteria for study entry.

Thus, although the present "neutral" findings may not mirror that of the other studies, and the trial was likely underpowered, "the results of TESLA complement and extend those of the recent prior trials," according to an by Tudor Jovin, MD, and colleagues of Cooper University Health Care in Camden, New Jersey.

"Compared with earlier trials, TESLA had broader, more pragmatic entry criteria. It was the only trial to extend the enrollment window to 24 hours while requiring only noncontrast CT for infarct size estimation and CT angiography for diagnosis of target vessel occlusion without more advanced imaging techniques to identify patients for entry," the editorialists wrote.

American guidelines currently recommend certain advanced imaging criteria for mechanical thrombectomy in selected patients with acute ischemic stroke with large vessel occlusion in the anterior circulation.

"Removing the requirement for advanced imaging as a selection tool for thrombectomy in the extended time window would significantly reduce barriers in access to thrombectomy worldwide," Jovin's group surmised. However, the editorialists said that yet more research needs to be done, including on how thrombectomy would fare when used on late-presenting stroke patients with large infarcts.

TESLA was a phase III open-label trial conducted at 47 stroke thrombectomy centers in the U.S. from 2019 to 2022.

Participants were 300 people with large infarcts identified on noncontrast CT. Eligibility criteria included an anterior-circulation proximal artery occlusion, a time window of 0 to 24 hours from last seen well, age younger than 85, an NIH Stroke Scale (NIHSS) score of 6 or higher, and Alberta Stroke Program Early CT Scores (ASPECTS) of 2 to 5 -- therefore excluding people with the largest of the large infarcts.

The cohort randomized to thrombectomy or usual care was 46% women and had a median age of 67. The median baseline NIHSS score was 19. Of note, there was some disagreement between site and the core laboratory over ASPECTS, so over 10% of people were ultimately judged to have had baseline ASPECTS >5 by core laboratory.

One in five people received IV alteplase under the recommended early time window.

Ultimately, 90-day mortality rates were 35.3% with thrombectomy versus 33.3% with usual care. Symptomatic intracranial hemorrhage in 24 hours reached 4.0% versus 1.3%, respectively, indicating some excess risk in the intervention arm.

"Given the higher incidence of hemorrhagic complications seen with thrombectomy across these trials and the limited benefit of thrombolysis prior to thrombectomy beyond the ultra-early time window, investigating the benefit and safety of bridging intravenous thrombolysis prior to thrombectomy in patients with a large-core is necessary," Jovin's group commented.

Meanwhile, the secondary endpoint of proportion of 90-day mRS score range of 0 to 2 favored the thrombectomy arm (14.6% vs 8.9%).

Zaidat and colleagues reported a higher point estimate of benefit when the intervention was performed in the 0- to 6-hour time window, but they could not back this up with evidence of a significant treatment effect modification by presentation time on post hoc analysis.

The main results of TESLA were initially reported at the 2023 meeting.

Comment