WORKSHOP OUTLINE

Workshop Objective

The field is at an inflection point. Three major Western RCTs have produced largely neutral functional outcomes for thrombectomy in broad MeVO/DisVO populations, while ORIENTAL-MeVO and DISTALS suggest that patient context, IVT availability, technique, and purpose-built devices may meaningfully alter the signal. This workshop will synthesize the evidence, identify areas of agreement and equipoise, and define the questions that should guide future trials, registries, regulatory pathways, and clinical practice.

Topic 1 — Vessel Size: Definitions, Classification, and Imaging

The lack of a shared MeVO/DisVO taxonomy limits cross-trial comparison, weakens guideline development, and creates confusion in clinical practice. A practical consensus definition should combine anatomy, vessel caliber, dominance, and imaging accessibility.

1A. Definitions: Where the Field Stands

• Segment-based definitions: ACA A1–A3, PCA P1–P3, mid/distal M2, M3/M4.
• Diameter-based definitions: typically ≥1 mm and endovascularly accessible.
• Dominance-based definitions: dominant M2 may behave clinically like LVO and may warrant separate classification.
• DISTAL definition: co- or non-dominant M2, M3/M4, A1–A3, and P1–P3.
• Persistent divergence: proximal M2 is classified as LVO by some groups and MeVO by others.

Key Discussion Questions

1. Can we agree on a practical definition of MeVO and DisVO for future trials and registries?
2. Should proximal or dominant M2 be excluded from MeVO definitions and treated as LVO-equivalent?
3. Should vessel dominance be mandatory for inclusion/exclusion decisions in trials?
4. Should DisVO and MeVO be combined under one operational category, or studied separately?

1B. Imaging Detection and Standardization

• CTA remains the clinical standard; multiphase CTA may improve collateral and distal branch assessment.
• CTP is useful when CTA is equivocal or when cortical wedge-shaped deficits suggest distal occlusion.
• DISTALS used CTP-based reperfusion of threatened tissue, shifting the endpoint from simple vessel patency to tissue reperfusion.
• AI-assisted detection is increasingly used, but small-vessel performance requires prospective validation.
• MRI/DWI may be valuable for posterior circulation and tissue characterization, but acute availability is variable.

Key Discussion Questions

1. Should CTP be mandatory for MeVO trial enrollment or reserved for selected cases?
2. Can CTP-based reperfusion serve as a primary endpoint in early-phase trials?
3. Which AI imaging tools are mature enough for prospective MeVO workflows?
4. What minimum imaging protocol should be required for future DisVO/MeVO registries?

Topic 2 — Evidence Review: What Do the Trials Actually Tell Us?

The trial results should not be interpreted as a single binary answer. They differ by geography, IVT exposure, device strategy, endpoint selection, NIHSS distribution, and occlusion subtype. The goal is to identify which neutral findings are definitive and which reflect limitations of trial design or technology.

2A. Three Neutral Trials: DISTAL, ESCAPE-MeVO, DISCOUNT

• Convergent neutral results across three independent Western trials are a real signal and should temper routine broad adoption.
• Low-to-moderate NIHSS enrollment likely created a ceiling effect for mRS 0–2 and diluted treatment effect.
• Absence of screening logs leaves uncertainty about selection bias and real-world denominator.
• High IVT use in controls may have reduced the incremental benefit of MT, especially for smaller clot burdens.
• Standard stent retrievers were not designed for vessels <2 mm; ESCAPE-MeVO mandated SR first pass, potentially constraining technique.

Key Discussion Questions

1. Does DISTAL 12-month neutrality close the door on broad MeVO MT, or simply refine the population?
2. Should future trials require NIHSS ≥6, ≥8, or ≥10 to enrich for measurable benefit?
3. How much of the neutral signal is explained by IVT-responsive thrombi and mild deficits?
4. Should future trials mandate screening logs and consecutive enrollment?

2B. Positive Functional Signal: ORIENTAL-MeVO

• 563 patients in China; EVT versus medical management.
• Positive 90-day functional outcome, unlike the three neutral Western trials.
• Most control patients did not receive IVT, potentially isolating the MT effect more clearly.
• Operator choice allowed technique flexibility rather than mandating a single device approach.

Key Discussion Questions

1. Does ORIENTAL-MeVO reflect a true MT effect in IVT-limited settings, or differences in selection, practice, or disease biology?
2. Should Western trials include an IVT-ineligible or IVT-deferred stratum?
3. How generalizable are these findings to North American and European systems?

2C. Purpose-Built Device Signal: DISTALS

• 118 randomized patients in the United States and Europe; IVT-ineligible population.
• Tigertriever 13 is an adjustable, purpose-built device for distal vessels <2 mm.
• Primary endpoint: reperfusion success without sICH at 24 hours using CTP-based assessment.
• Strong positive reperfusion and safety signal; 90-day mRS data pending.
• The result suggests device design and target population may be central to future trial success.

Key Discussion Questions

1. Does DISTALS prove that purpose-built distal devices were the missing link?
2. Is CTP-based reperfusion plus safety sufficient for regulatory progress, or must functional benefit be shown first?
3. How should clinicians act on a strong reperfusion signal while awaiting functional data?
4. Should the next trial begin now or wait for mature 90-day outcomes?

2D. Cross-Trial Synthesis

1. Prioritize a patient-level meta-analysis across DISTAL, ESCAPE-MeVO, DISCOUNT, and ORIENTAL-MeVO.
2. Pre-specify subgroup analyses by time-to-treatment, NIHSS, occlusion location, IVT eligibility, and device strategy.
3. Reconcile the field’s core tension: three neutral Western trials, one positive Chinese trial, and one positive device-based reperfusion trial.

Topic 3 — Patient Selection, Technique, and Technology

Current evidence does not support indiscriminate MeVO thrombectomy. It does support a more disciplined question: which patients, treated how early, with which device, and under which IVT conditions are most likely to benefit?

3A. Patient Selection

• Dominant M2 occlusion with NIHSS ≥6 remains the most LVO-like scenario.
• IVT-ineligible patients with accessible target vessels represent a high-priority study population.
• Earlier-presenting patients may derive greater benefit based on ESCAPE-MeVO post hoc data.
• High-NIHSS MeVO with large mismatch may better capture clinically meaningful salvageable tissue.
• Posterior circulation MeVO may require separate study because anatomy, deficits, and outcomes differ.

Key Discussion Questions

1. What NIHSS threshold should define meaningful clinical severity: 6, 8, or 10?
2. Should IVT eligibility be a formal stratification variable or trial exclusion criterion?
3. What treatment window is practical and biologically plausible for MeVO?
4. Should posterior circulation MeVO be studied in a dedicated protocol?

3B. Technique

• Standard stent retrievers may carry higher hemorrhagic or perforation risk in smaller, fragile vessels.
• Contact aspiration and cyclical aspiration techniques are improving but require stronger comparative evidence.
• Adjustable/purpose-built devices such as Tigertriever 13 may reduce distal-vessel trauma and improve reperfusion.
• Intra-arterial thrombolytics remain underexplored and may deserve a dedicated arm or adjunct strategy.

Key Discussion Questions

1. Should purpose-built devices or aspiration-first strategies be required in future trials?
2. Should intra-arterial lytics be tested as a separate treatment arm?
3. How should centers without distal-specific devices approach selected MeVO patients pending new data?

3C. Technology and Innovation

• Future regulatory pathways may need vessel-size-specific evidence for devices used below 2 mm.
• Key design features include lower profile, adjustable radial force, improved trackability, reduced retrieval tension, and minimized endothelial injury.
• Robotic-assisted navigation is early but may eventually improve distal access and expand remote expertise.

Key Discussion Questions

1. Should regulatory agencies require device-specific trials for vessels <2 mm?
2. Which device features should be considered essential for next-generation distal thrombectomy?
3. How should the field balance urgent patient need with the obligation to await functional data?

Topic 4 — Endpoints and Future Trial Design

Endpoint choice may be the central methodological issue for the next generation of MeVO trials. Dichotomized mRS 0–2 is often insensitive in mild MeVO populations, while tissue-based and domain-specific outcomes may better capture clinically meaningful benefit.

4A. The Endpoint Problem

• mRS 0–2 has a ceiling effect because many MeVO patients achieve independence without intervention.
• mRS may miss language, cognition, visual field, and fine-motor deficits that matter to patients.
• mRS shift is more sensitive than dichotomized mRS and should be favored when feasible.
• CTP-based reperfusion may be appropriate for Phase 2 or regulatory feasibility, but functional outcome remains essential for clinical adoption.
• Adjunct endpoints should include early neurological improvement, infarct volume, domain-specific PROs, return to work, and 90/180-day function.

Key Discussion Questions

1. Should CTP-based reperfusion plus safety be a Phase 2 primary endpoint, with functional outcome reserved for Phase 3?
2. Should mRS shift replace mRS 0–2 as the universal primary functional endpoint?
3. Which patient-reported outcomes best capture cortical MeVO deficits?
4. Should DWI infarct volume be co-primary or a powered secondary endpoint?
5. Is early neurological improvement a valid surrogate for 90-day outcome in MeVO?

4B. Procedural and Safety Endpoints

1. Should eTICI 2c/3 be the target in MeVO, or is eTICI 2b sufficient?
2. Should the sICH definition differ from LVO trials given smaller vessels and often smaller infarcts?
3. Should perforation, vasospasm, dissection, and distal embolization be pre-specified safety endpoints?

4C. Future Trial Design Priorities

• Enrich population by NIHSS threshold and clinically meaningful deficit.
• Exclude or stratify by IVT eligibility to better isolate MT effect.
• Require consecutive enrollment and mandatory screening logs.
• Separate or stratify non-dominant M2, M3, ACA, PCA, and posterior circulation MeVO.
• Consider adaptive designs that allow population refinement and early stopping for futility or efficacy.
• Mandate device strategy if testing a purpose-built technology hypothesis.

Key Design Questions

1. Is patient-level meta-analysis a prerequisite before launching the next pivotal trial?
2. Should the intervention be a mandated purpose-built distal device?
3. What minimum clinically meaningful effect size would justify adoption?
4. What sample size and enrollment period are realistic?