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 in patients with large-core ischaemic stroke presenting up to 24 h after onset?
Bottom Line
Endovascular thrombectomy improves 90-day functional outcomes and reduces mortality vs medical management in patients with large-core ischaemic stroke presenting within 24 h, without an increase in symptomatic intracranial haemorrhage. Benefit was sustained across ASPECTS and ischaemic core strata up to 150 mL; evidence remains limited for core volumes ≥150 mL beyond 6 h.
Major Points
- Individual patient data meta-analysis of 6 RCTs, 1886 patients with large-core ischaemic stroke (ASPECTS ≤5 or ischaemic core ≥50 mL) within 24 h
- EVT improved 90-day mRS distribution: aGenOR 1.63 (95% CI 1.42-1.88, p<0.0001)
- Reduced 90-day mortality: 31.1% (EVT) vs 37.3% (medical); aRR 0.82 (95% CI 0.70-0.97, p=0.022)
- No increase in symptomatic intracranial haemorrhage: 1.1% vs 1.0% (risk difference -0.17 pp, p=0.69)
- No significant difference in early neurological worsening (24-48 h): 22.0% vs 17.9% (aRR 1.19, p=0.27)
- NNT 4.2 to improve ≥1 mRS point; NNT 8.6 for functional independence (mRS 0-2); NNT 5.7 for independent ambulation (mRS 0-3); NNT 14.6 for reduced mortality
- Successful reperfusion (eTICI 2b-3) achieved in 82.7% of EVT-treated patients
- Benefit consistent across age, NIHSS, occlusion site (ICA vs MCA), hemisphere, time window, ASPECTS strata (0-2, 3, 4, 5, 6-10), and presence or absence of perfusion mismatch
- Benefit sustained for ischaemic core volumes up to 150 mL; for core ≥150 mL, point estimates favoured EVT (especially 0-6 h) but wide CIs limited interpretation
- Central imaging core laboratory readjudicated ASPECTS, ischaemic core volume, perfusion mismatch, and haemorrhagic transformation across all trials
Design
Study Type: Systematic review and individual patient data meta-analysis with central imaging adjudication
Randomization: 1
Blinding: Central imaging adjudicators masked to treatment group, source trial, and original core laboratory ASPECTS readings
Allocation: Individual trial-level randomisation; meta-analysis based on intention-to-treat allocation
Enrollment Period: Trials published between March 1, 2018 and March 1, 2025
Follow-up Duration: 90 days (primary outcome); 1-year outcomes planned in dedicated analysis
Centers: 0
Countries:
Sample Size: 1886
Analyzed: 1886
Analysis: Intention-to-treat; two-stage random-effects meta-analysis using REML; primary outcome analysed with probabilistic index models (PIMs) adjusted for age, NIHSS, time from last-known-well to randomisation, and ASPECTS; missing data handled by multiple imputation (chained equations, 30 datasets, Rubin's rule); sensitivity analyses with best-case and worst-case imputation; as-treated sensitivity analysis
Registration: PROSPERO CRD420251058584
Inclusion Criteria
- Adult patients with acute ischaemic stroke due to anterior circulation large-vessel occlusion
- Large-core ischaemic stroke: ASPECTS ≤5 on non-contrast CT or MR diffusion, OR estimated ischaemic core volume ≥50 mL on CT perfusion or MR diffusion
- Within 24 h of time last known to be well
- Randomly allocated to endovascular thrombectomy or best medical care
- Enrolled in randomised trials published March 1, 2018 to March 1, 2025
Arms
| Field | Endovascular Thrombectomy | Control |
|---|---|---|
| N | 944 | 942 |
| Intervention | Endovascular thrombectomy plus standard medical care | Best medical management without endovascular thrombectomy |
| Duration | Acute intervention | Acute intervention |
Outcomes
| Outcome | Type | Control | Intervention | HR / OR / RR | P-value |
|---|---|---|---|---|---|
| Distribution of modified Rankin Scale (mRS) scores at 90 days (mRS scores 5 and 6 merged into one category) | Primary | Median mRS 5 (IQR 4-6), n=931 | Median mRS 4 (IQR 3-6), n=940 | 1.63 | <0.0001 |
| Functional independence (mRS 0-2) at 90 days | Secondary | NNT 8.6 (95% CI 6.2-14.1) | |||
| Independent ambulation (mRS 0-3) at 90 days | Secondary | NNT 5.7 (95% CI 4.7-7.2) | |||
| All-cause mortality at 90 days | Secondary | 347/931 (37.3%) | 292/940 (31.1%) | 14.6 (95% CI 7.5-326.3) | 0.022 |
| Successful reperfusion (eTICI 2b-3) in EVT-treated patients | Secondary | 771/932 (82.7%, 95% CI 80.2-85.0) | |||
| Symptomatic intracranial haemorrhage within 36 h (parenchymal haematoma type 2 with ≥4-point NIHSS increase or death, or subarachnoid haemorrhage) | Safety | 9/942 (1.0%) | 10/944 (1.1%) | 0.69 | |
| Neurological worsening (≥4-point NIHSS increase at 24-48 h) | Safety | 161/899 (17.9%) | 197/896 (22.0%) | 0.27 | |
Subgroup Analysis
Improved functional outcomes with EVT were consistent across prespecified subgroups: age (<70 vs ≥70 years), sex, occlusion location (ICA vs MCA), NIHSS (<20 vs ≥20), hemisphere, time window (dichotomised at 6 h and 12 h), ASPECTS strata (0-2, 3, 4, 5, 6-10), and presence/absence of perfusion mismatch (both mismatch profiles). Benefit was sustained for ischaemic core volumes <70, 70-100, and 100-150 mL. For ischaemic core ≥150 mL, point estimates favoured EVT particularly in the 0-6 h window, but wide 95% CIs limited interpretation. No effect modification by age, stroke severity, occlusion site, or affected hemisphere.
Criticisms
- Wide 95% CIs for ischaemic core volume ≥150 mL subgroup limit interpretation, particularly beyond 6 h
- Some concerns for risk of bias for secondary outcome of neurological worsening due to missing data in two trials
- Perfusion mismatch status available for only 56.1% of patients
- 1-year outcomes not uniformly collected; planned in dedicated analysis
- Heterogeneity in original trial eligibility criteria (different imaging modalities, time windows, ASPECTS/core volume thresholds)
- 95% CIs for secondary outcomes and subgroup analyses not adjusted for multiple comparisons
Funding
None
Based on: ATLAS (The Lancet, 2026)
Authors: Sarraj A, Thomalla G, Yoshimura S, ..., Parsons MW
Citation: Sarraj A, et al. 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. The Lancet. Available online 7 May 2026.
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