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EMBOLISE 2

EMBOLISE 2: Middle Meningeal Artery Embolisation versus Observation in Mildly Symptomatic Chronic Subdural Haematoma

Year of Publication: 2026

Authors: Jared Knopman, Jason Davies, et al.

Journal: Presented at the 2026 International Stroke Conference (ISC)


Clinical Question

Does middle meningeal artery embolisation (MMAe) reduce the composite of surgical drainage need, poor clinical outcome, or clinical deterioration compared to observation alone in mildly symptomatic chronic subdural haematoma patients?

Bottom Line

MMAe resulted in a twofold reduction in the composite primary endpoint compared to observation at 90 days in mildly symptomatic cSDH patients, with significant haematoma volume reduction at 180 days, though procedural stroke risk (5.9%) warrants attention to optimized technique and maintenance of antithrombotic therapies.

Major Points

  • EMBOLISE 2 is the first trial specifically powered to study MMAe in mildly symptomatic cSDH patients.
  • Primary composite endpoint was halved with MMAe vs observation (11.9% vs 23.2%) at 90 days with a NNT of 9.
  • All three individual components of the composite endpoint showed comparable or greater reduction with MMAe.
  • MMAe failed non-inferiority for mRS deterioration at 90 days but achieved it at 180 days.
  • Haematoma volume at 180 days was nearly halved with MMAe (43.8 ml vs 80 ml).
  • Stroke rate was 5.9% in MMAe vs 0% in observation; 5 of 6 strokes were deemed preventable.
  • Key lessons: do not stop antithrombotic medications, keep the MMAe procedure simple, and avoid unnecessary catheterizations.
  • Patients with higher Charlson comorbidity index scores were at greater risk for stroke and negative outcomes.
  • Neurologic death rates were comparable between groups; no deaths in MMAe arm were attributed to Onyx or haematoma.
  • EMBOLISE 1 previously led to FDA-updated indication for Onyx in non-acute SDH.

Design

Study Type: Prospective, multicentre, randomized controlled trial

Randomization: 1

Blinding: Open-label (not blinded)

Follow-up Duration: 180 days

Centers: 60

Countries: USA

Sample Size: 200


Inclusion Criteria

  • Chronic subdural haematoma (cSDH)
  • Mildly symptomatic presentation
  • Haematoma volume ≤15 ml
  • Midline shift <5 ml

Exclusion Criteria

  • Severe motor weakness

Arms

FieldMMAeControl
InterventionUpfront middle meningeal artery embolisation with Onyx liquid embolic agentObservation only (conservative management)
Duration

Outcomes

OutcomeTypeControlInterventionHR / OR / RRP-value
Composite of need for surgical drainage, poor clinical outcome, or clinical deterioration at 90 daysPrimary23.2%11.9%11.30%
mRS deterioration (non-inferiority) at 90 daysSecondaryFailed non-inferiority
mRS deterioration (non-inferiority) at 180 daysSecondaryAchieved non-inferiority
Haematoma volume at 180 daysSecondary80 ml43.8 mlStatistically significant
StrokeAdverse0%5.9% (6 events)
Neurologic DeathAdverseComparable4 deaths (none attributed to Onyx or haematoma)Not statistically significant

Subgroup Analysis

Patients with elevated Charlson comorbidity index (CCI) scores had greater stroke risk. Of the 6 strokes in MMAe arm: 3 occurred in patients whose antithrombotic medications were withheld, 2 were due to internal carotid artery catheterization complications (1 dissection, 1 embolic shower), and 1 was related to underlying comorbidities. No strokes were related to Onyx.


Criticisms

  • Open-label design with no blinding.
  • 5.9% stroke rate in MMAe arm vs 0% in observation raises safety concerns.
  • Trial was not powered to assess individual components of the composite endpoint.
  • Baseline characteristics not reported in available data.
  • Exact p-values and confidence intervals for primary endpoint not provided in available presentation data.
  • Mildly symptomatic population may limit generalizability to more severe cSDH patients.

Funding

Medtronic (Onyx liquid embolic agent)

Based on: EMBOLISE 2 (Presented at the 2026 International Stroke Conference (ISC), 2026)

Authors: Jared Knopman, Jason Davies, et al.

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