Fabiano Cavalcante, MD, is a PhD candidate at Amsterdam UMC and founder of Citadel Medical Sciences.

Fabiano Cavalcante, MD

Prior intravenous thrombolysis (IVT) did not significantly modify the functional effects of endovascular therapy (EVT) in patients with 

medium and distal vessel occlusion (MDVO) stroke

, according to a new analysis of the DISTAL trial.

Intravenous Thrombolysis Does Not Modify Endovascular Therapy for MDVO Strokes

 in Seoul, South Korea, by Fabiano Cavalcante, MD, a PhD candidate at Amsterdam UMC and founder of Citadel Medical Sciences, these exploratory data may indicate that the threshold for procedural intervention in distal occlusions may be higher than previously believed.

“It’s very important that these results should be interpreted carefully,” Cavalcante told 

 in an exclusive interview. “I think they are more on the hypothesis-generating side than actually on the treatment decision side. We need more evidence from pooling these trials together to have a larger sample size or randomizing further patients, especially now that we know the results of the first 3 trials that didn’t show a clear benefit.”

DISTAL was an open-label, randomized trial conducted across 56 locations worldwide. Patients were eligible for inclusion if they had experienced an acute ischemic stroke and had evidence of a hypoperfusion-hypodensity mismatch, a diffusion-hyperintensity mismatch, and isolated medium vessel occlusion, among other criteria. Patients with acute intracranial hemorrhage, an in-hospital stroke, known history of arterial tortuosity or pre-existing stent, among other criteria, were excluded.

Patients were randomly assigned to receive either EMT on top of standard therapy, including IVT or antiplatelet therapy if indicated, or standard therapy alone. The primary endpoint was the degree of dependency and disability in everyday life at 90 days, which investigators measured via the modified Rankin Scale (mRS). Secondary endpoints included the change in National Institutes of Health Stroke Scale (NIHSS) at 24 hours post-randomization, assessment of cognitive function via the Montreal Cognitive Assessment (MoCA) at 90 days, and change in quality of life at 90 days.

A total of 543 patients were enrolled in DISTAL, of whom 271 were assigned to the treatment arm and 272 to the control arm. Median NIHSS score at admission was 6 (interquartile range [IQR], 5-9), and 355 patients received IVT. Predominant occlusion locations were the M2 (n = 239), M3 (n = 146), P2 (n = 73), and P1 (n = 30) segments.

By 12 months, investigators found no difference in the distribution of mRS scores between the groups (adjusted common OR 0.81; 95% CI, 0.59-1.12; 

 = .2). The median mRS score was 2 (IQR, 1-4) in the treatment group and 2 (IQR, 1-4) in the control group. In the treatment arm, 58 of 263 patients who completed the study showed an improvement of ≥1 point between 90 days and 12 months, compared to 56 of 261 patients in the control arm. Another 56 patients in the treatment arm and 47 in the control arm saw mRS scores worsen by ≤1 point.

In the present analysis, Cavalcante and colleagues included patients from the DISTAL trial with non-minor stroke, defined as NIHSS >5. The primary outcome of the analysis was functional status at 90 days, analyzed using adjusted ordinal regression. Interaction terms also assessed whether the treatment effect was modified by prior IVT use and by baseline NIHSS among those ineligible for IVT.

Of the 543 patients included in DISTAL, 319 had an admission NIHSS >5 and were included in the study. Of these, 216 received IVT. No significant interaction was observed between treatment assignment and prior IVT use for 90-day mRS (ratio of odds ratios [rOR], 0.56; 95% CI, 0.24-1.32; 

-interaction = 0.18). Among patients ineligible for IVT, however, Cavalcante and colleagues did see a significant interaction between treatment allocation and baseline NIHSS (rOR = 1.49; 95% CI, 1.18-1.9; 

-interaction <.001) with EVT associated with improved functional outcomes as stroke severity increased.

Ultimately, Cavalcante and colleagues concluded that prior IVT did not significantly modify the functional effect of EVT in these patients. Among those who were ineligible, however, the benefit of EVT was very dependent on baseline severity, appearing most favorable in those patients with moderate-to-severe deficits (NIHSS >10).

“At the level of hypothesis generation, I think these results do mean that we maybe need at least a moderately severe stroke to justify the risks of IVT procedures in a more fragile, more distal vessel, which carries risks of complications,” Cavalcante said. “But again, I think it’s very important to reiterate that this study does not define whether you should treat a patient based on the NIHSS or not.”

Editors’ Note: Cavalcante reports no relevant disclosures.

Cavalcante F. Endovascular Therapy for Non-Minor MDVO Stroke in Patients Ineligible for Intravenous Thrombolysis: A Secondary Analysis of the DISTAL Randomized Clinical Trial. Presented at the World Stroke Congress (WSC) 2026, Seoul, South Korea. October 21-23, 2026.

Fischer U, Brehm A, Ribo M, et al. Endovascular treatment for medium or distal vessel occlusion stroke (distal): 12-month outcomes of a multicentre, open-label, randomised trial. 

University Hospital, Basel, Switzerland. EnDovascular Therapu Plus Best Medical Treatment (BMT) Versus BMT Alone for MedIum VeSsel Occlusion sTroke (DISTAL). ClinicalTrials.gov Identifier: NCT05029414. Updated December 24, 2024. Accessed October 21, 2026. 

https://clinicaltrials.gov/study/NCT05029414

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Fabiano Cavalcante, MD, discusses his secondary analysis of the DISTAL trial, which revealed minimal association between IVT and the effect of EVT in MDVO strokes.

Fabiano Cavalcante, MD

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