AURORA
(2026)Objective
Evaluate the association between treatment times (onset-to-randomization, onset-to-puncture, onset-to-reperfusion, randomization-to-reperfusion) and 90-day functional outcomes in patients undergoing endovascular thrombectomy (EVT) for anterior-circulation large-vessel occlusion (LVO) stroke in the extended (6–24-hour) time window.
Study Summary
• Functional independence (mRS 0–2): EVT vs control 47.5% vs 25.8% (6–12h), 45.9% vs 8.5% (12–16h), 35.7% vs 4.2% (16–24h); p-interaction<0.001
• Safety: sICH ~4–6% across epochs with no significant time association; 90-day mortality similar between arms overall (~18–20%) with no significant time effect
Intervention
Endovascular thrombectomy (EVT) with second-generation neuro-thrombectomy devices vs best medical therapy, in patients selected largely by advanced (perfusion/mismatch) imaging in the 6–24-hour extended window.
Inclusion Criteria
Anterior-circulation LVO with moderate-to-severe deficits and small-to-moderate infarct volume randomized 6–24 hours from time last known well; enrolled in one of 6 modern EVT RCTs (DAWN, DEFUSE 3, ESCAPE, REVASCAT, POSITIVE, RESILIENT); treated with second-generation thrombectomy devices.
Study Design
Arms: Endovascular thrombectomy (EVT) vs medical therapy alone
Patients per Arm: EVT 266, Control 239 (total 505)
Outcome
• Functional independence (mRS 0–2): EVT 47.5% vs 25.8% (6–12h), 45.9% vs 8.5% (12–16h), 35.7% vs 4.2% (16–24h); p-interaction<0.001
• Randomization-to-reperfusion time in EVT: mRS shift aOR 0.58 (0.37–0.91) per 60 min, p=0.018; mRS 0–2 aOR 0.51 (0.28–0.96), p=0.038
• Safety: sICH ~4–6%, no time association; 90-day mortality not significantly different by time
Bottom Line
Endovascular thrombectomy provides substantial benefit in patients with anterior circulation large vessel occlusion stroke across the 6–24 hour time window when imaging evidence of reversible cerebral ischemia is present. Thrombectomy should not be withheld on the basis of advanced age, moderate infarct size, mode of presentation, or point in time within the 6–24 h window.
Major Points
- Individual patient data meta-analysis of 6 RCTs including 505 patients randomized beyond 6 h from time last known well
- Primary outcome (mRS ordinal shift at 90 days) favored thrombectomy: adjusted cOR 2.54 (95% CI 1.83–3.54; p<0.0001); NNT = 3
- Functional independence (mRS 0–2, secondary) more than doubled: 45.9% vs 19.3% (adjusted OR 3.88, 1.94–7.78; p<0.0001)
- No increase in mortality (16.5% vs 19.3%; adjusted OR 0.96, p=0.88) or symptomatic ICH (5.3% vs 3.3%; adjusted OR 1.74, p=0.23)
- Treatment effect was stronger in the 12–24 h window (cOR 5.86) than 6–12 h (cOR 1.76); p-interaction=0.0087
- No heterogeneity of effect across age, gender, NIHSS, occlusion site, ASPECTS, or mode of presentation (wake-up, witnessed, unwitnessed)
- Findings support broadening eligibility for thrombectomy across the 6–24 h window in patients with evidence of salvageable brain tissue
Study Design
- Study Type
- Systematic review and individual patient data meta-analysis of randomized controlled trials
- Randomization
- Yes
- Sample Size
- 505
- Follow-up
- 90 days
- Countries
- USA, Canada, France, Spain, Ireland, South Korea, UK, Brazil
Primary Outcome
Definition: Disability on the modified Rankin Scale (mRS) at 90 days, analyzed by mixed-effects ordinal logistic regression (shift analysis across the full 0–6 mRS distribution)
| Control | Intervention | HR/OR | P-value |
|---|---|---|---|
| n=239; mRS shift distribution at 90 days (see Figure 1) | n=266; mRS shift distribution at 90 days (see Figure 1) | 2.54 (1.83–3.54 (adjusted cOR); 1.76–3.33 (unadjusted cOR 2.42)) | <0.0001 |
Limitations & Criticisms
- Heterogeneous imaging selection criteria across included trials — some required advanced perfusion imaging (DAWN, DEFUSE 3), others relied on ASPECTS alone
- Small contributions from four of the six trials (ESCAPE n=49; RESILIENT, POSITIVE, REVASCAT each ~21–26) — pooled estimates driven largely by DAWN and DEFUSE 3
- Findings apply only to patients with imaging evidence of reversible cerebral ischemia; generalizability to unselected late-window patients cannot be inferred
- Four included trials (DEFUSE 3, ESCAPE, POSITIVE, REVASCAT) were stopped early, raising possibility of treatment-effect overestimation
- Funded by Stryker Neurovascular, a manufacturer of thrombectomy devices — potential for sponsorship bias
Citation
Lancet 2022; 399: 249–58. Published Online November 11, 2021.