Endovascular Therapy Fails in Distal Occlusion Stroke

Use of endovascular thrombectomy offered no benefit in patients with acute ischemic stroke caused by occlusions in distal vessels, findings from three new randomized trials showed. 

The treatment, which involves mechanically removing the clot, has been established as highly effective in patients with large vessel occlusion stroke. It was hoped that this positive treatment effect could be extended to patients with stroke due to occlusions in the smaller vessels further down the arterial tree, but this has not been the case. 

The three trials were all presented February 5 at the International Stroke Conference (ISC) 2025, being held this week in Los Angeles. The two larger trials, DISTAL and ESCAPE-MeVO, were also published online simultaneously in the New England Journal of Medicine. 

These two trials yielded very similar results, both showing a neutral outcome, with no major benefit or harm suggested with the endovascular therapy compared with medical treatment alone. 

The third trial, DISCOUNT, was stopped early because of a suggestion of harm. Results presented at the ISC meeting indeed showed a worse outcome in the endovascular group. 

“The two larger trials — DISTAL and ESCAPE-MeVO — show exactly the same conclusion — a neutral outcome. This means the results are reliable,” senior investigator of the DISTAL trial, Urs Fischer, MD, University Hospital Bern, Switzerland, told Medscape Medical News. 

“The endovascular treatment did not appear to cause significant additional harm in our study. That means if we can find groups who benefit, this approach may have a role in future. But at present we cannot recommend its routine use in patients with these distal occlusions based on these results,” added DISTAL lead investigator, Marios Psychogios, MD, University Hospital Basel, Switzerland, in comments to Medscape. 

The leaders of the ESCAPE trial agreed.

“At the current time, we need to be super careful about considering endovascular therapy in these patients with distal occlusions, especially because the DISCOUNT trial suggested possible harm,” Mayank Goyal, MD, University of Calgary, Canada, lead investigator of the ESCAPE trial, told Medscape Medical News. 

Senior investigator, Michael Hill, MD, MSc, University of Calgary, Canada, pointed out that the two larger trials showed higher risks of bleeding and other safety outcomes with endovascular treatment “but these were not large enough to explain the profoundly neutral overall result,” he said in an interview.

Hill suggested that future trials need to focus on patient subgroups who may benefit and trying to improve reperfusion rates. 

“ No one doubts that better reperfusion leads to better outcomes. In the DISTAL and ESCAPE trials reperfusion rates were around 72-75% in the endovascular arms — there is scope for improvement here which could be dependent on new devices and improved operator skills,” Hill said. 

Fischer highlighted the unmet need in these patients with distal occlusions. 

“I don’t think this is the end of the story,” he commented. “In our trial, 45% of patients with these distal artery occlusions had a poor outcome (severe disability or death). This must drive us to find new solutions.” 

DISTAL Trial

The DISTAL trial included 543 participants (44% women; median age, 77 years) with acute ischemic stroke caused by an isolated occlusion of medium or distal vessels, who were randomized to endovascular therapy (mostly stent retrievers) or best medical treatment alone within 24 hours of symptom onset or last known well — provided that neuroimaging suggested salvageable tissue. 

The median score on the National Institutes of Health Stroke Scale admission was 6, and IV thrombolysis was given to 65.4% of the participants.

The primary outcome was the level of disability at 90 days, as assessed with the modified Rankin scale (mRS) score, and this was not significantly different between the two groups, with a common odds ratio (OR) for improvement in the score of 0.90 (95% CI, 0.67-1.22; P =.50). 

All-cause mortality was not significantly different in the two groups (15.5% with endovascular therapy; 14% with best medical treatment alone). Symptomatic intracranial hemorrhage was numerically increased in the endovascular group (5.9% and 2.6%), but this again was not significant. 

ESCAPE-MeVO trial 

The ESCAPE trial included 530 patients with acute ischemic stroke due to medium-vessel occlusion (85% had primary occlusions in a middle-cerebral-artery branch) who presented within 12 hours from the time that they were last known to be well and who had favorable baseline non-invasive brain imaging to receive endovascular therapy using the Solitaire X device plus usual care or usual care alone.

The primary outcome was a favorable outcome (mRS score 0 or 1) at 90 days. This occurred in 41.6% in the endovascular group and in 43.1% in the usual-care group (adjusted rate ratio, 0.95; 95% CI, 0.79-1.15; P =.61).

Mortality at 90 days was 13.3% in the endovascular group and 8.4% in the usual-care group (adjusted hazard ratio, 1.82; 95% CI, 1.06-3.12). Symptomatic intracranial hemorrhage occurred in 5.4% of the endovascular group and in 2.2% of the usual-care group.

The ESCAPe-MeVO authors suggest several possible reasons for the lack of benefit with endovascular therapy in this study, including a higher rate of serious adverse events — which could have resulted in the higher mortality observed in the endovascular group — and the observation that technical endovascular therapy success could not be achieved in all cases, with around one quarter of the patients in the endovascular group having incomplete reperfusion. 

They also point out that technical challenges in accessing the occluded vessel may have delayed reperfusion, particularly in smaller, distal occlusions. “The implication is that endovascular therapy may have been performed too late, at a point at which the volume of salvageable tissue may not have been large enough to result in significantly better outcomes,” investigators wrote.

DISCOUNT Trial 

Findings from the French DISCOUNT trial were presented at ISC by Frédéric Clarençon, MD, Pitié Salpêtrière Hospital, Paris. The study included patients with an acute ischemic stroke related to a distal vessel occlusion within 6 hours of symptom onset or within 24 hours if salvageable brain tissue was identified. Participants were randomized to endovascular therapy or best medical treatment alone (control). The trial was stopped after 163 patients were enrolled because of a suggestion of harm in the endovascular group and low power to show a benefit.

Interim results showed that the primary outcome — the rate of good clinical outcome at 3 months (mRS score ≤ 2) — occurred in 60% of the endovascular group vs 77% of the control arm. 

After multiple imputation of missing data, a harmful effect of endovascular therapy was seen, with an OR of a good clinical outcome of 0.42 (95% CI, 0.2-0.88; P = .024. A per-protocol sensitivity analysis showed an OR of 0.30 (95% CI, 0.12-0.74; P = .009.

Symptomatic intracranial hemorrhage was numerically higher in the endovascular group (12% vs 6%).

‘Ground Zero’ 

The trial investigators are hoping to pool the results from the three trials for further analysis. 

“Perhaps a phoenix can rise out of the ashes,” Goyal said. “These trials of distal occlusions can be very difficult to perform as there can be huge heterogeneity in terms of the area of the brain affected. There is no obvious subgroup that shows a benefit at the moment, but we are planning to merge all the data together from the three studies that will enable a more detailed look at subgroups,” he added. 

A fourth Chinese trial in patents of endovascular therapy in patents with distal occlusion stroke is ongoing, so more data will be available in due course. 

Hill believes further trials will be conducted, but they will probably need larger sample sizes and to plan for a smaller effect size than these initial trials. 

In an accompanying editorial in NEJM, J Mocco, MD, Icahn School of Medicine, Mount Sinai Health System, New York, notes that uptake of endovascular therapy for distal occlusion has been increasing in clinical practice and suggests that physicians may have chosen not to randomize potentially eligible patients with substantial deficits. 

“No matter how one considers these data, there is no question that they represent the current ground zero of evidence to inform decision making regarding the use of thrombectomy for stroke due to medium- and distal-vessel occlusion. The data clearly show that thrombectomy for distal-vessel occlusions should not be an assumed default care pathway,” Mocco concluded. 

The DISTAL trial was funded by the Swiss National Science Foundation Gottfried und Julia Bangerter-Rhyner-Stiftung, Medtronic, Stryker Neurovascular, Phenox, Rapid Medical, and Penumbra. The ESCAPE-MeVO trial was supported by grants to the University of Calgary from the Canadian Institutes for Health Research and Medtronic. The DISCOUNT trial was funded by the French Ministry of Health with devices supplied by Stryker, Phenox, Penumbra, Balt, AB Medica, MiVi, and Cerenovus). 

Psychogios reports grants/speaker fees from from Stryker, Medtronic, Phenox, Penumbra, Rapid Medical, and Acandis. Fischer reports grants from Medtronic, Stryker, Rapid medical, Penumbra, Medtronic and Phenox for the DISTAL trial. Goyal and Hill report grants from Medtronic for the ESCAPE-MeVO trial. Clarençon reports lectures fees/consultancies from Balt, Penumbra, Stryker, Cerenovus, Medtronic, Microvention, board member of Artedrone, and stock options in Intradys, LetsGetProof. Rocco reports payments from Medtronic, for the purchase of two start-up companies, consulting fees from Imperative Care, research funding from MicroVention, Penumbra, and Stryker.