Endovascular Therapy Eyed for Milder Strokes, Later Time Window

— Chinese trials back yet more avenues to expand stroke therapy

Endovascular therapy (EVT) made promising forays into milder and later-presenting large vessel occlusion (LVO) strokes in a pair of multicenter, open-label trials from China.

In the MILD-MTopens in a new tab or window trial of people with mild acute ischemic stroke (AIS), performing EVT within 24 hours of stroke onset alongside medical management was more likely to result in excellent patient functional outcomes (modified Rankin scale score 0 or 1) at 90 days compared with medical management alone (69.4% vs 50.0%; OR 2.32, 95% CI 1.41-3.81), reported Jianmin Liu, MD, PhD, of Changhai Hospital, Naval Medical University in Shanghai, and colleagues.

Meanwhile, in the LATE-MTopens in a new tab or window trial, with AIS patients showing salvageable brain tissue in the infarct 24-72 hours after symptom onset, EVT added to standard medical care was also associated with better functional outcomes (common OR 1.74, 95% CI 1.19-2.55), according to Pengfei Yang, MD, also of Changhai Hospital.

The caveats were safety signals that could not be ignored: There was no excess risk of symptomatic intracranial hemorrhage (ICH) but a greater risk of serious procedural complications in MILD-MT, whereas ICH and deaths came out disproportionately higher after EVT in LATE-MT.

The two trials were published in the New England Journal of Medicine.

In an accompanying editorialopens in a new tab or window, Gaultier Marnat, MD, of Bordeaux University Hospital in France, called LATE-MT and MILD-MT "important advances" in a field that has sought to expand its range since the landmark thrombectomy trials in 2015.

For nearly a decade, EVT has been indicated for AIS due to an LVO in the anterior circulation within 24 hoursopens in a new tab or window of the time last known to be well. Earlier this year, the American stroke guidelineopens in a new tab or window expanded the eligibility for EVT to patients with larger ischemic coreopens in a new tab or window and basilar occlusionopens in a new tab or window strokes on the basis of new evidence.

With EVT's boundaries pushed to yet new settings, the safety incidents in LATE-MT and MILD-MT are not necessarily deal-breakers, Marnat suggested.

For one, LATE-MT showed that symptomatic ICH occurred in 4.8% of those in the EVT group and none of the control patients. Deaths at 90 days reached 6.0% and 1.8%, respectively.

Marnat's defense was that the LATE-MT investigators had had IV thrombolysis administered to over 10% of patients despite the late time window, as well as anticoagulant or antithrombotic therapy given to the majority of patients within the first 24 hours after randomization.

"This finding indicates a need for caution when administering antithrombotic therapies in patients being considered for late endovascular therapy," the editorialist wrote.

It also remains to be seen how non-Asian populations, in whom cardioembolism is the more common cause of LVO, will fare with EVT for mild strokes and later time windows, according to Marnat.

More answers are expected from the MOSTEopens in a new tab or window and SELECT LATEopens in a new tab or window trials, both still ongoing in France and the U.S.

MILD-MT

Liu and colleagues conducted their study at 26 comprehensive stroke centers in China and had 304 people randomized to EVT plus medical management or medical management alone in 2024 and 2025. Study participants were selected for having mild anterior circulation strokes and substantial at-risk tissue on perfusion imaging within 24 hours after symptom onset or after they were last known to be well.

The MILD-MT trial cohort came out to 300 individuals in the modified intention-to-treat population (median age in the mid-to-late 60s, over 70% men). At baseline, the median NIH Stroke Scale Score was 4.0, and median ASPECTS was 9.0. Median infarct core volume was 1.5-1.8 mL and perfusion-mismatch volume 103.9 mL. Time from stroke onset to randomization was about 8.5 hours.

Of note, despite randomization, there was a between-group imbalance in the proportion of people with previous stroke or transient ischemic attack (20.8% in the EVT group vs 11.5% for controls) and those who received IV thrombolysis (25.0% vs. 35.3%).

The EVT group achieved successful reperfusion (expanded Thrombolysis in Cerebral Infarction [eTICI] grade 2b to 3) in 93.8% of cases.

Symptomatic ICH within 48 hours occurred in three patients in each group, and the one death occurred in the EVT group. Serious procedure-related complications occurred in 13.2% of the EVT group: most commonly arterial dissection (5.6%), subarachnoid hemorrhage (2.8%), and embolization in a new territory (2.1%).

"Still, the net benefit-risk ratio in the treatment of acute LVO appears to favor endovascular therapy," Marnat commented.

He also highlighted the reduction in 7-day neurologic deterioration observed with EVT (13.9% vs 31.4%; OR 0.36, 95% CI 0.20-0.64). "This finding was consistent with observational data showing that, despite the mild initial severity, acute LVO with minor symptoms is not a benign condition. These patients have a substantial risk of subsequent neurologic worsening, and EVT was shown to reduce this risk in this trial."

LATE-MT

Separately, testing the boundaries for late EVT, Yang's group conducted the LATE-MT trial at 35 comprehensive stroke centers in China. Investigators recruited AIS patients with LVO of the anterior circulation and imaging-identified salvageable brain tissue at 24-72 hours. As in MILD-MT, participants were assigned to receive EVT plus medical management or standard medical care alone.

Ultimately, 336 made it into the intention-to-treat population (mean age 64 years, roughly 30% women). Their median time from symptom onset to randomization was 38.5 hours. Median NIH Stroke Scale Score at baseline was 10-11, ASPECTS on noncontrast CT was 8, infarct volume 4.0-5.0 mL, and perfusion-lesion volume 120 mL. Nearly 80% of the cohort had good collateral status on CT angiography.

EVT recipients achieved postprocedure reperfusion (eTICI 2b50 to 3) in 94.6% of cases.