ATLAS
Endovascular thrombectomy for patients with large-core ischaemic stroke presenting up to 24 h after onset (ATLAS): a systematic review and individual patient data meta-analysis with central imaging adjudication
Clinical Question
Does endovascular thrombectomy improve functional outcomes and reduce mortality versus medical management in patients with large-core ischaemic stroke presenting up to 24 h after onset?
Study Overview
Objective
To synthesize evidence from recent trials evaluating endovascular thrombectomy versus medical management in patients with large-core ischaemic stroke presenting within 24 h of onset, and to estimate treatment benefit within clinical and imaging subgroups.
Study Summary
- Endovascular thrombectomy improved 90-day mRS distribution vs medical management (median 4 [IQR 3-6] vs 5 [4-6]; aGenOR 1.63, 95% CI 1.42-1.88, p<0.0001)
- Mortality was reduced with thrombectomy (31.1% vs 37.3%; aRR 0.82, 95% CI 0.70-0.97, p=0.022)
- No significant difference in symptomatic ICH (1.1% vs 1.0%; risk difference -0.17 pp, 95% CI -1.01 to 0.67, p=0.69) or early neurological worsening (22.0% vs 17.9%; aRR 1.19, 95% CI 0.87-1.62, p=0.27)
- Benefit was consistent across ASPECTS and ischaemic core strata up to 150 mL; evidence limited above 150 mL beyond 6 h, though point estimates favoured thrombectomy
- NNT: 4.2 (95% CI 3.3-5.8) to improve ≥1 mRS point; 14.6 (7.5-326.3) to reduce mortality
Intervention
Endovascular thrombectomy vs best medical management in patients with large-core ischaemic stroke (ASPECTS ≤5 or ischaemic core ≥50 mL) presenting within 24 h of onset.
Patients per Arm
944 vs 942
Bottom Line
Endovascular thrombectomy improves functional outcomes and reduces mortality versus medical management in patients with large-core ischaemic stroke (ASPECTS ≤5 or core ≥50 mL) presenting within 24 h of onset, with benefit sustained across ASPECTS and ischaemic core strata up to 150 mL; evidence is limited for very extensive ischaemia (core ≥150 mL) beyond 6 h.
Major Points
- Individual patient data meta-analysis of 6 randomised trials with 1886 patients with large-core ischaemic stroke
- Endovascular thrombectomy improved 90-day mRS distribution (aGenOR 1.63, 95% CI 1.42-1.88, p<0.0001)
- Thrombectomy reduced all-cause 90-day mortality (31.1% vs 37.3%; aRR 0.82, 0.70-0.97, p=0.022)
- No increase in symptomatic intracranial haemorrhage (1.1% vs 1.0%) or early neurological worsening
- Benefit consistent across age, stroke severity, occlusion site, hemisphere, ASPECTS, perfusion mismatch, and core volume up to 150 mL
- NNT 4.2 (3.3-5.8) to improve by ≥1 mRS point; 8.6 (6.2-14.1) for functional independence; 14.6 (7.5-326.3) to reduce mortality
- Evidence limited above 150 mL core volume, though point estimates remained favourable
- Central imaging core laboratory re-adjudicated ASPECTS, ischaemic core, perfusion mismatch, and haemorrhagic transformation
Design
Study Type: Systematic review and individual patient data meta-analysis with central imaging adjudication
Randomization: 1
Blinding: Central imaging readers masked to treatment group, source trial, and prior ASPECTS assignment
Allocation: As per individual randomised trials
Enrollment Period: Literature search window: trials published between March 1, 2018 and March 1, 2025 (patient enrollment period not reported)
Follow-up Duration: 90 days
Centers: 0
Countries:
Sample Size: 1886
Analyzed: 1886
Analysis: Two-stage meta-analysis with random-effects model; primary outcome (90-day mRS distribution) analysed using adjusted pooled generalised odds ratios (aGenORs); missing data handled by multiple imputation; safety outcomes reported as adjusted pooled relative risk (aRR) and risk difference
Registration: PROSPERO CRD420251058584
Inclusion Criteria
- Adult patients with acute ischaemic stroke due to anterior circulation large-vessel occlusion
- Large-core ischaemic stroke defined by ASPECTS ≤5 on non-contrast CT or MR diffusion, OR estimated ischaemic core volume ≥50 mL on CT perfusion or MR diffusion
- Randomization within 24 h of the time patient was last known to be well
- Randomly allocated to endovascular thrombectomy or best medical care
Exclusion Criteria
- Included trials excluded patients with established oedema with mass effect (results do not apply to those patients)
- Patients with pre-existing disability were not included
- Some individual trials excluded additional subgroups such as patients older than 80 years or with ASPECTS 0-2
Arms
| Field | Endovascular thrombectomy | Control |
|---|---|---|
| N | 944 | 942 |
| Intervention | Endovascular thrombectomy plus best medical management | Best medical management alone |
| Duration |
Outcomes
| Outcome | Type | Control | Intervention | HR / OR / RR | P-value |
|---|---|---|---|---|---|
| Distribution of 90-day modified Rankin Scale (mRS) scores | Primary | Median mRS 5 (IQR 4-6); n=931 | Median mRS 4 (IQR 3-6); n=940 | 4.2 | <0.0001 |
| Functional independence (mRS 0-2) at 90-day follow-up | Secondary | 70/931 (7.5%) | 183/940 (19.5%) | 8.6 | <0.0001 |
| Independent ambulation (mRS 0-3) at 90-day follow-up | Secondary | 185/931 (19.9%) | 343/940 (36.5%) | 5.7 | <0.0001 |
| All-cause mortality within 90-day follow-up period | Safety | 347/931 (37.3%) | 292/940 (31.1%) | 14.6 | 0.022 |
| Symptomatic intracranial haemorrhage within 36 h of randomisation | Safety | 9/942 (1.0%) | 10/944 (1.1%) | Risk difference -0.17 percentage points | 0.69 |
| Neurological worsening within 24-48 h of randomisation | Safety | 161/899 (17.9%) | 197/896 (22.0%) | aRR 1.19 | 0.27 |
Subgroup Analysis
Improved functional outcomes with endovascular thrombectomy were consistent across clinical and imaging subgroups, including age, stroke severity, site of arterial occlusion, hemisphere, ASPECTS, and perfusion imaging mismatch. Benefit was seen for ischaemic core volumes up to 150 mL across the 0-24 h time window. For core volumes ≥150 mL, point estimates favoured thrombectomy (particularly in the 0-6 h window), but wide 95% CIs limited interpretation.
Criticisms
- Evidence for patients with very extensive ischaemic injury (core ≥150 mL), particularly beyond 6 h, remains limited with wide confidence intervals
- Heterogeneity in imaging modalities and eligibility criteria across included trials
- Time windows and outcome measures varied between the six included trials
- Trials excluded patients with established oedema with mass effect and those with pre-existing disability, limiting generalisability to those groups
Funding
None
Based on: ATLAS (The Lancet, 2026)
Authors: Sarraj A, Thomalla G, Yoshimura S, ..., for the ATLAS Investigators
Citation: Lancet 2026; 407: 2015-26
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