Two randomised trials presented at the International Stroke Conference (ISC; 5–7 February, Los Angeles, USA) have indicated that mechanical thrombectomy treatments confer no advantages over the current standard of care for acute ischaemic strokes caused by distal- or medium-vessel occlusions (D/MeVOs). Final analyses of the ESCAPE-MeVO study revealed that thrombectomy failed to produce an improvement in patients’ clinical outcomes, while the DISCOUNT study was halted early due to safety concerns and indications of futility with the procedure.
With the DISTAL trial—also presented for the first time at ISC 2025—finding that thrombectomy was safe but did not improve disability-related outcomes versus the current standard of care, a total of three separate studies have now provided evidence suggesting that the procedure adds little clinical value in D/MeVO stroke.
“Few procedures have gone through a decade of practice-changing clinical trials as impressive as thrombectomy for stroke,” writes J Mocco (Mount Sinai Health System, New York City, USA) in an editorial accompanying the publication of ESCAPE-MeVO and DISTAL in the New England Journal of Medicine (NEJM). “Beginning in 2015 with multiple trials showing a benefit with thrombectomy in early large-vessel occlusion, followed by the extended-window trials in 2018 and then the large-core trials in 2023, it seemed that no corner of the cerebrovasculature would not have a substantial benefit from a proper clot removal—until now.
“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.”
ESCAPE-MeVO results
Presented by Mayank Goyal and Michael Hill (both University of Calgary, Calgary, Canada) on the first day of ISC 2025, the randomised, open-label, blinded-endpoint ESCAPE-MeVO trial enrolled a total of 530 D/MeVO patients across the USA, Canada, Germany, Hungary and the UK. Enrolled patients were allocated to either thrombectomy plus medical management or medical management alone. The study’s primary endpoint was the rate of functional independence at 90-day follow-up, as per a score of 0–1 on the modified Rankin scale (mRS).
Goyal relayed that the rates of mRS 0–1 at 90 days were statistically similar between the two study arms; 41.6% with thrombectomy versus 43.1% without. The investigators report an unadjusted risk ratio (RR) of 0.97 and an adjusted RR of 0.95 on this front. In his presentation, Goyal also detailed an average 90-day mRS score of 2 in both groups. Regarding a handful of efficacy-related secondary endpoints, he noted that 90-day rates of mRS 0–2 were comparable between the thrombectomy group (54.1%) and the medical management group (58.8%), while mortality rates at the same timepoint were slightly higher with thrombectomy (13.3%) versus without (8.4%).
ESCAPE-MeVO’s safety endpoint data also revealed that patients who received a thrombectomy experienced an increased rate of serious adverse events (33.9%) compared to those who did not (25.7%), with pneumonia being the most common of these events. Additionally, while major procedural complications were “rare”, rates of recurrent stroke (5.4% vs 3.7%), stroke progression (5.4% vs 1.8%) and symptomatic intracranial haemorrhage (ICH; 5.4% vs 2.2%) were also higher in the thrombectomy group. Analyses of patient subgroups in the trial revealed no statistical heterogeneity between the two treatment arms regarding age, sex, geographical region, baseline stroke severity, occlusion location, infarct volume, or use of intravenous thrombolytics; but, there was a trend towards improved outcomes with thrombectomy in patients presenting within an earlier time window (onset to randomisation, <260 minutes).
Writing in NEJM, the ESCAPE-MeVO investigators echo Mocco’s suggestion that the results of their trial “do not support routine endovascular treatment of acute ischaemic stroke due to medium-vessel occlusion”, going on to aver that further work is needed to improve the safety profile of the thrombectomy procedure and identify a population of patients who may benefit from this approach.
DISCOUNT analyses
Taking to the ISC podium immediately after Goyal, Frédéric Clarençon (Pitié-Salpêtrière University Hospital, Paris, France) detailed findings from the DISCOUNT study—a prospective, multicentre, open-label, randomised controlled trial that sought to enrol a total of 488 D/MeVO stroke patients across 22 French centres. Similarly to ESCAPE-MeVO, the study’s aim was to evaluate thrombectomy plus medical management versus medical management alone via a primary endpoint relating to 90-day disability. However, the DISCOUNT investigators opted for the broader endpoint of a ‘good’ clinical outcome (mRS 0–2).
A planned interim analysis of the trial on the first 163 randomised patients for whom a three-month follow-up visit was available led to it being stopped, with early data appearing to “disfavour” thrombectomy. Clarençon relayed that safety-related concerns and indications of low conditional power resulted in the data safety monitoring board (DSMB) recommending that the trial should be halted. Following multiple imputations and adjustments on minimisation factors, a modified intention-to-treat population of 163 patients was ultimately available for analysis.
Across this population, Clarençon reported an observed 90-day rate of mRS 0–2 of 60% in the study’s thrombectomy arm versus 77% in the medical management arm, leading—after imputation of missing data—to an odds ratio (OR) of 0.42 (p=0.024). Per-protocol sensitivity analysis also revealed an OR of 0.3 (p=0.009) pertaining to the study’s primary endpoint.
Additional analyses suggested a comparable median length of hospital stay between the two study groups—eight days in both—while evaluations of DISCOUNT’s ‘as-treated’ population found higher rates of at least one serious adverse event (39% vs 31%), as well as all ICHs (44% vs 29%) and symptomatic ICHs (12% vs 6%), with thrombectomy. However, the mortality rate was lower in the thrombectomy group (3%) versus the non-thrombectomy group (7%).
Clarençon concluded by noting that, while there did appear to be a potential deleterious effect with thrombectomy in terms of 90-day functional outcomes, this did not reach statistical significance on their interim analysis, adding that analyses of the trial’s overall population are “ongoing”.
The findings of ESCAPE-MeVO, DISCOUNT and DISTAL are likely to leave many asking the same question posed by Mocco in his recent NEJM editorial: “Where do we go from here?”
“The authors of the ESCAPE-MeVO trial correctly emphasise the importance of rigorously conducted randomised controlled trials,” he adds. “The stroke community should not be complacent. Rather, we must thoroughly test appropriate questions, evaluate alternative approaches, and not allow bias to interfere with identifying the best treatment strategies for patients with stroke. Let us not forget that almost half of all the enrolled patients in these trials had substantial disability at 90 days. There remains a continuing mandate, with more work required, to study how we can improve outcomes in patients. These two trials [ESCAPE-MeVO and DISTAL] prove that their patient populations did not have a benefit with thrombectomy and, as such, performance of thrombectomy for medium- or distal-vessel occlusion in a manner consistent with these trials is not evidence-based. Further effort—grounded in high-quality data science—is needed to evaluate alternative approaches for medium- or distal-vessel occlusion, be they medical or procedural.”
