Endovascular Therapy Hits a Wall for Stroke Clots Lodged in Mid-Size Vessels

LOS ANGELES — Contrary to expectations, the benefits of endovascular thrombectomy (EVT) did not extend to strokes related to mid-size vessel occlusions, as shown independently by two randomized trials.

EVT failed to improve clinical outcomes when tested in patients with acute ischemic strokes attributed to medium- or distal-vessel occlusions in the DISTAL trial, in which the procedure conferred no better distribution of modified Rankin Scale (mRS) scores at 90 days over best medical therapy (common OR for improvement 0.90, 95% CI 0.67-1.22), reported Marios Psychogios, MD, of University Hospital Basel, and Urs Fischer, MD, MSc, of the University Hospital Bern, both in Switzerland.

Similarly, among patients with medium-vessel occlusion strokes in ESCAPE-MeVO, the EVT group was no more likely than controls to log favorable mRS scores of 0-1 at 90 days (41.6% vs 43.1%, adjusted RR 0.95, 95% CI 0.79-1.15), with the median score being 2 in both groups, according to Mayank Goyal, MD, PhD, and Michael Hill, MD, both of the University of Calgary in Canada.

Besides the lack of effectiveness, there were signals of risk from EVT in these trial populations: in DISTAL, all-cause mortality was numerically higher with EVT (15.5% vs 14.0% with standard care), while death rates were significantly higher in ESCAPE-MeVO (13.3% vs 8.4%, adjusted HR 1.82, 95% CI 1.06-3.12).

The outcome of symptomatic intracranial hemorrhage also favored usual care over EVT in both DISTAL (2.6% vs 5.9%) and ESCAPE-MeVO (2.2% vs 5.4%).

Both were presented as high-profile, multicenter trials at the International Stroke Conference and simultaneously published in the New England Journal of Medicine.

“The results show the outer limits of mechanical thrombectomy efficacy to the main large intracranial vessels. Unless further technical improvements or ability to select potential subgroups of patients with higher benefits, mechanical thrombectomy should no longer be performed in this setting,” said Pierre Fayad, MD, of University of Nebraska Medical Center in Omaha, who was not involved with either trial.

The present data from DISTAL and ESCAPE-MeVO mark a stark departure for EVT, which has a strong track record — based on about a decade of positive randomized trials and observational reports — of good safety and effectiveness in large vessel occlusion strokes.

“At this time, with these results, mechanical thrombectomy for distal intracranial (mid-size vessel) occlusions, in general, should not be performed with the purpose of improving patient clinical outcomes in the setting of acute ischemic stroke. The potential trend for increased risks of symptomatic intracranial hemorrhage and mortality is concerning on top of the lack of efficacy,” Fayad told MedPage Today in an email.

DISTAL included 543 people with an isolated occlusion of medium or distal vessels. After meeting imaging criteria, participants were randomized to receive EVT (the device or technique left to each operator) or best medical treatment alone within 24 hours after the participant was last seen to be well. Exclusion criteria included patients who were bedridden or coming from a nursing facility, in-hospital strokes, and any vessel recanalization prior to randomization.

The study cohort ended up having 44% women and a median age of 77 years. The median NIH Stroke Scale score was 6 at admission. Represented occlusion locations were the M2 segment (44.0%) or M3 segment (26.9%) of the middle cerebral artery (MCA), as well as the P2 segment (13.4%), and P1 segment (5.5%) of the posterior cerebral artery.

EVT and medical therapy groups had been randomized at a median 3.8 and 4.0 hours, respectively, since last seen well, and IV thrombolysis was administered to 62.0% and 68.8%. Of the EVT cohort, 71.7% achieved successful reperfusion.

“We were surprised at the overall outcome of the participants, which was worse than we anticipated based on retrospective data,” Psychogios said in a press release. “While the results of the DISTAL trial might seem discouraging, we see it as a wake-up call to continue investigating treatment options for medium or distal vessel occlusion patients as outcomes appear to be more severe than expected and evidence-based effective treatment options are still lacking.”

Indeed, people with medium vessel occlusions tend to have a poor prognosis, with half of people not achieving excellent clinical outcomes with standard care, which includes thrombolytic therapy.

The ESCAPE-MeVO participants were 530 people with symptomatic strokes attributed to medium-vessel occlusion who presented within 12 hours of symptom onset. Exclusion criteria included any intracranial hemorrhage at baseline, a major comorbid illness, and people not living independently at home. Investigators had also avoided secondary medium vessel occlusions, namely those that used to be large vessel occlusions, because they are thought to involve more extensive ischemic changes and may not benefit from thrombectomy and IV thrombolysis.

Median age was around 75 years, and just over 46% were women. The median NIH Stroke Scale score was 7 in the control group and 8 in the EVT group. Baseline ASPECTS was 10 and 9, respectively. The occluded vessels were largely a mix of M2 and M3 segments of the MCA.

The ESCAPE-MeVO patients had been randomized to standard care with or without EVT more than 4 hours after symptom onset. IV thrombolysis was given to 60.2% of controls and 56.5% of the EVT group. The EVT group achieved successful reperfusion in 75% of cases, stent retrievers having been mandated as the first-line approach.

“The two trials, in spite of different design, different times of enrollment, different vessels treated, show consistent lack of efficacy,” Fayad commented. While similar studies are ongoing, he predicted that “it is likely that the ongoing studies will have to stop randomizing patients and have an interim analysis of the obtained data so far, reviewed by the [data and safety monitoring board], to see whether it is ethical to continue the studies.”

To explain EVT’s failure so far in medium vessels, Mayank surmised that it is possible that these vessels are more like end arteries needing an earlier time window for treatment. There were also technical limitations in the current EVT workflow, he suggested, and the quality of recanalization may be improved in the future.

In an editorial, J. Mocco, MD, of Mount Sinai Health System in New York City, characterized the DISTAL and ESCAPE-MeVO cohorts as being older and having higher baseline disability, which may have reduced the potential benefit of thrombectomy.

“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 stressed.

Hill said the ESCAPE-MeVO trial is ongoing with plans for a 1-year follow-up.

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