Endovascular Therapy Shows Promise for Mild Strokes and Extended Time Windows, but Safety Concerns Persist

• Two randomized trials investigated endovascular treatment (EVT) in previously untested scenarios: clinically mild strokes and a 24- to 72-hour time window.
• Both studies demonstrated significant functional benefits with EVT, though each raised distinct safety concerns, including procedural complications and increased hemorrhage rates.
• Ongoing trials are expected to further clarify the risk-benefit profile of EVT in these expanded indications.

Endovascular therapy (EVT) has made promising inroads into the treatment of mild and late-presenting large vessel occlusion (LVO) strokes, according to a pair of multicenter, open-label trials conducted in China.

In the MILD-MT trial, which enrolled patients with mild acute ischemic stroke (AIS), performing EVT within 24 hours of symptom onset alongside medical management yielded superior functional outcomes at 90 days—defined as a modified Rankin Scale score of 0 or 1—compared with medical management alone (69.4% vs. 50.0%; odds ratio 2.32, 95% CI 1.41–3.81). The findings were reported by Jianmin Liu, MD, PhD, of Changhai Hospital, Naval Medical University in Shanghai, and colleagues.

Meanwhile, the LATE-MT trial evaluated AIS patients with salvageable brain tissue identified on imaging 24 to 72 hours after symptom onset. Adding EVT to standard medical care was also associated with better functional outcomes (common odds ratio 1.74, 95% CI 1.19–2.55), according to Pengfei Yang, MD, also of Changhai Hospital.

However, safety signals emerged that cannot be overlooked. MILD-MT showed no excess risk of symptomatic intracranial hemorrhage (ICH) but a higher rate of serious procedural complications. In contrast, LATE-MT reported disproportionately higher rates of ICH and mortality in the EVT arm.

Both trials were published in the New England Journal of Medicine.

In an accompanying editorial, Gaultier Marnat, MD, of Bordeaux University Hospital in France, hailed LATE-MT and MILD-MT as “important advances” in a field that has sought to expand its scope since the landmark thrombectomy trials of 2015.

For nearly a decade, EVT has been indicated for anterior-circulation AIS due to LVO within 24 hours of the time last known well. Earlier this year, American stroke guidelines broadened eligibility to include patients with larger ischemic cores and basilar-occlusion strokes based on new evidence.

As EVT’s boundaries extend further, the safety incidents observed in LATE-MT and MILD-MT are not necessarily deal-breakers, Marnat suggested.

For instance, LATE-MT found symptomatic ICH occurred in 4.8% of EVT patients versus none in the control group, while 90-day mortality reached 6.0% and 1.8%, respectively.

Marnat noted that over 10% of LATE-MT participants received intravenous thrombolysis despite the late time window, and the majority received anticoagulant or antithrombotic therapy within 24 hours of 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—among whom cardioembolism is a more common cause of LVO—will fare with EVT for mild strokes and extended time windows, according to Marnat.

Further answers are anticipated from the ongoing MOSTE and SELECT LATE trials in France and the United States.

MILD-MT

Liu and colleagues conducted their study at 26 comprehensive stroke centers in China, randomizing 304 patients to EVT plus medical management or medical management alone in 2024 and 2025. Participants were selected for mild anterior-circulation strokes with substantial at-risk tissue on perfusion imaging within 24 hours of symptom onset or last known well.

The modified intention-to-treat population comprised 300 individuals (median age in the mid-to-late 60s, over 70% men). At baseline, the median NIH Stroke Scale score was 4.0, median ASPECTS was 9.0, median infarct core volume was 1.5–1.8 mL, and perfusion-mismatch volume was 103.9 mL. Median time from stroke onset to randomization was approximately 8.5 hours.

Despite randomization, imbalances emerged: prior stroke or transient ischemic attack was more common in the EVT group (20.8% vs. 11.5%), while intravenous thrombolysis was administered less frequently (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 per group, and the single death occurred in the EVT arm. Serious procedure-related complications arose in 13.2% of EVT recipients, most commonly arterial dissection (5.6%), subarachnoid hemorrhage (2.8%), and embolization to 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 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 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

Yang’s group conducted the LATE-MT trial at 35 comprehensive stroke centers in China, recruiting AIS patients with anterior-circulation LVO and imaging-identified salvageable brain tissue at 24–72 hours. As in MILD-MT, participants were assigned to EVT plus medical management or standard medical care alone.

The intention-to-treat population included 336 patients (mean age 64 years, roughly 30% women). Median time from symptom onset to randomization was 38.5 hours. Baseline median NIH Stroke Scale score 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 post-procedure reperfusion (eTICI 2b50 to 3) in 94.6% of cases.

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