At February’s International Stroke Conference in Los Angeles, the biggest news was presented at the opening session: thrombectomy is no better than medical management for medium-vessel occlusions (MeVOs). Three randomized-controlled trials, ESCAPE-MeVO, DISTAL, and DISCOUNT, found no clinical benefit with thrombectomy for distal- or medium-vessel occlusions (D/MeVOs).

1. Endovascular Treatment for Distal-/Medium-Vessel Occlusion (D/MeVO)

Since 2015, when multiple trials found benefit from early thrombectomy in large vessel occlusion, the indications for endovascular therapy (EVT) have expanded at a rapid pace, with benefit demonstrated in the extended window in 2018 and in large-core infarcts in 2023. The field may be nearing the limitations of clot retrieval (at least with existing technology), with three trials now failing to show benefit for medium- or distal-vessel occlusions. Importantly, one of the three trials, ESCAPE-MeVO, also demonstrated higher mortality in the thrombectomy group (13.3% vs. 8.4% in the medical management group; adjusted hazard ratio 1.82 [95% CI, 1.06-3.12]). All three trials showed numerically higher rates of symptomatic ICH. 

DISTAL, presented by Marios Psychogios (University Hospital Basel, Basel, Switzerland), was a randomized, open-label European trial that randomized 543 patients with D/MeVO (M2, M3, M4, A1, A2, A3, P1, P2, P3; patients with dominant M2 occlusions were excluded) presenting within 24h of last known well time (LKWT) to EVT plus medical management (MM) or MM alone. Primary outcome was distribution of modified Rankin Scale (mRS) scores at 90 days. Common OR for improvement in mRS was 0.90 (95% CI 0.67-1.22, p=0.50). There was no difference in mortality (15.5% with EVT vs. 14% without), and a numerically higher rate of symptomatic ICH (5.9% vs. 2.6%) did not reach statistical significance.

ESCAPE-MeVO, presented by Mayank Goyal (University of Calgary, Calgary, AB, Canada), was a randomized, open-label, blinded-endpoint trial which enrolled 530 D/MeVO patients in the US, Canada, and Europe. Patients with distal and medium vessel occlusions (M2, M3, A2, M3, P2, P3; no exclusion for dominant M2) presenting within 12h of LKWT were randomized to EVT plus MM or MM alone. The primary endpoint was functional independence (mRS 0-1) at 90 days. Functional independence was achieved by 41.6% of the EVT group and 43.1% of the MM only group (adjusted risk ratio 0.95 [95% CI, 0.79-1.15]; p=0.61). Rates of mRS 0-2 were also similar between the two groups (54.1% in the EVT group vs. 58.8% in the MM only group), but mortality was higher in the EVT group (13.3% vs. 8.4% in MM only, HR 1.82 [95% CI, 1.06-3.12]), as were rates of serious adverse events, recurrent stroke, stroke progression, and symptomatic ICH.

DISCOUNT, presented by Frédéric Clarençon (Pitié-Salpêtrière Hospital, Paris, France), was an open-label, randomized controlled trial in France comparing medical management with or without thrombectomy in D/MeVO stroke patients. Trial results are not yet published. The trial was stopped early after a planned interim analysis of 163 patients (from an anticipated 488 enrolled patients) showed lower rates of good clinical outcome (mRS 0-2) at 90 days with EVT. A modified intention-to-treat population of 163 patients with 3-month follow-up data yielded a 90-day mRS of 0-2 in 60% of the EVT group and 77% of the MM only group, leading to an OR of 0.42 for good functional outcome (p=0.024). Mortality was lower in the thrombectomy group (3% vs. 7%), but rates of at least one serious adverse event (39% vs. 31%) and symptomatic ICH (12% vs. 6%) were higher in the thrombectomy group.

2. MIND Trial Preliminary Results

During the opening session, results of the Minimally Invasive Surgery for Deep and Lobar Intracranial Hemorrhages (MIND) Trial were presented by David Fiorella (Stony Brook University Hospital, Stony Brook, New York). Results are not yet published. MIND was a multicenter, open-label randomized controlled trial of patients with moderate to large volume supratentorial ICH (20-80 cc) presenting within 24h of symptom onset. Patients were randomized 2:1 to minimally invasive surgery with the ARTEMIS device within 72h or medical management. The MIND trial was stopped early after the results of ENRICH were released, with 236 patients enrolled. The majority of enrolled patients (71%) presented with deep ICH, while 29% presented with lobar ICH. Primary outcome was ordinal mRS at 180 days.

Minimally invasive surgery (MIS) did not improve outcome at 180 days (OR for intention-to-treat population 1.03, 95% CI 0.62-1.72), though an early functional outcome benefit was seen at 30 days. This early beneficial effect may be attributable to reduced rates of symptomatic progression of perihematomal edema in the surgical group (2.6% vs. 13.4% in the MM group). There were also trends toward shorter hospital lengths of stay and lower intubation rates in the MIS arm. Surgical evacuation with the ARTEMIS device was effective, with a rate of hematoma evacuation of 81%. Mortality was low overall (7.2% in the MIS group vs. 9.8% in the MM group), with a trend toward decreased mortality in the MIS group among patients with lobar hemorrhage (8.3% vs. 22.7%).

Of note, the ENRICH trial showed that MIS for hematoma evacuation improved 6-month functional outcomes in patients with lobar hemorrhages; enrollment for deep hemorrhages was stopped early due to lack of benefit in this subgroup. The MIND trial failed to show a benefit for MIS evacuation for a mixed group of patients with more than twice as many deep as lobar hemorrhages. These results reinforce the lack of measurable benefit for hematoma evacuation in deep ICH.

3. Thrombolysis – Extending the Window and “Chasing” Thrombectomy

Late-Breaking Science trials were presented during ISC’s Closing Main Event. The most notable of these were trials related to thrombolysis. Two trials, ANGEL-TNK and PEARL, showed improvement in clinical outcome with thrombolysis administered after thrombectomy for large vessel occlusion stroke. The HOPE trial demonstrated efficacy and safety of alteplase in an extended time window between 4.5 to 24 hours for patients with salvageable tissue on perfusion imaging.

HOPE was a prospective, open-label, randomized controlled trial in China, enrolled 372 patients with acute ischemic stroke with mismatch indicating tissue at risk on perfusion imaging. Patients were randomized to alteplase or standard medical management between 4.5 and 24h after symptom onset. Among patients receiving alteplase in this late window, 40% achieved good functional recovery (mRS 0-1 at 90 days), compared to 26% with standard care. However, the study’s generalizability may be limited by population differences, including higher rates of intracranial atherosclerosis in China.

ANGEL-TNK was a prospective, open-label, blinded-endpoint, randomized controlled trial in China which enrolled 256 patients with LVO stroke presenting between 4.5 and 24h after LKWT who were successfully revascularized with EVT. Patients were randomized to intra-arterial TNK or standard medical management; none had received thrombolysis prior to EVT. The primary outcome was mRS 0-1 at 90 days. Rates of functional independence were higher in the TNK group (40.5% vs. 26.4% in the MM group, p=0.02). Rates of symptomatic ICH were similar in both groups at 48h (5.6% in the TNK group vs. 6.2% in the MM group).

PEARL was a multicenter, open-label trial in China which randomized 324 patients to intra-arterial alteplase vs. standard medical management after EVT for anterior circulation LVO presenting within 24h of LKWT. Primary outcome was mRS 0-1 at 90 days, and 42% received intravenous thrombolysis prior to EVT. The intervention group had higher rates of functional independence at 90 days compared with the medical management group (45% vs. 30%; RR 1.45, 95% CI 1.08-1.96, p=0.01). Rates of ICH and mortality were numerically but not statistically higher in the intervention group.

Of note, the results of two negative studies of thrombolytics following EVT, POST-TNK and POST-UK, were released in JAMA in February 2025. Stay tuned for upcoming summaries of these trials in Currents.