A treatment-response framework for interpreting endovascular thrombectomy evidence: established practice, boundary expansion and unresolved frontiers

This structured narrative review evaluates endovascular thrombectomy (EVT) through an author-developed, population-level treatment–response framework. In this framework, treatment response is the causal contrast between EVT plus best medical care and best medical care alone on a specified patient-centered outcome; it is not the outcome observed after EVT, and it cannot be observed for an individual patient because the untreated counterfactual is unknown. The framework is an evidence-interpretation tool, not a statistical estimator, a validated decision aid, or an individual prediction model. It separates four clinically actionable questions: first, trial eligibility—does the patient resemble a population in which EVT was tested; second, baseline prognosis—which features predict outcome under either strategy; third, procedural feasibility and safety—can reperfusion be achieved promptly at acceptable risk; and fourth, treatment-effect modification—does randomized evidence support a different relative or absolute effect across levels of a baseline variable? We conducted targeted, purposive searches across PubMed/MEDLINE, supplemented by backward and forward citation tracking, to identify pivotal randomized trials, individual participant data meta-analyses, population-specific guidelines, and directly relevant secondary analyses through 15 August 2026. Randomized evidence supports EVT for proximal anterior-circulation large-vessel occlusion in the early window, selected 6–24 h anterior-circulation populations, trial-defined large-core infarction, and selected moderate-to-severe basilar artery occlusion. Dedicated randomized evidence remains absent beyond 24 h and incomplete for large-vessel occlusion with a low National Institutes of Health Stroke Scale (NIHSS) score. ESCAPE-MeVO, DISTAL, and DISCOUNT did not demonstrate average functional benefit in broad medium/distal-vessel populations, whereas ORIENTAL-MeVO reported benefit in an enriched population with NIHSS at least 6; these results should not be generalized across all distal occlusions. Failure to detect an interaction does not establish homogeneous effects because interactions are outcome- and scale-specific, and most EVT trials are underpowered to detect them. Poor outcomes after successful reperfusion are descriptive of post-treatment states, not proof that EVT was futile. This framework clarifies what randomized evidence establishes, what remains prognostic or procedural, and where prospective testing is still required.