PDF: DAWN
(2018)Objective
To evaluate the efficacy of endovascular thrombectomy 6 to 24 hours after stroke onset in patients with a clinical–imaging mismatch.
Study Summary
Intervention
Endovascular thrombectomy with the Trevo device plus standard care vs standard care alone. Imaging-based eligibility required mismatch between NIHSS and infarct volume (measured by MRI or perfusion CT with RAPID).
Inclusion Criteria
Acute anterior circulation large-vessel occlusion, 6–24 hours from last known well, infarct core <21 mL (age ≥80), <31 mL (age <80, NIHSS ≥10), or <51 mL (age <80, NIHSS ≥20).
Study Design
Arms: Thrombectomy + Standard Care vs. Standard Care Alone
Patients per Arm: Thrombectomy: 107, Standard Care: 107
Outcome
Bottom Line
Endovascular thrombectomy plus standard care improved 90-day functional outcomes compared with standard care alone in patients presenting 6–24 hours after stroke onset with a clinical–core mismatch.
Major Points
- First RCT to show benefit of thrombectomy in the 6–24 hour window using clinical-core mismatch (RAPID automated perfusion software).
- Used Bayesian adaptive enrichment design with 3 mismatch groups: Group A (age ≥80, NIHSS ≥10, core <21 mL), Group B (age <80, NIHSS ≥10, core <31 mL), Group C (age <80, NIHSS ≥20, core 31–51 mL).
- Eligible vessels: intracranial ICA or proximal MCA (M1 segment) on CTA or MRA.
- Trial stopped early for efficacy after 206 of planned 500 patients — posterior probability of superiority exceeded 0.986.
- Primary outcome (utility-weighted mRS at 90 days): 5.5 vs 3.4 (adjusted difference 2.0, 95% credible interval 1.1–3.0, posterior probability >0.999).
- Functional independence (mRS 0–2) at 90 days: 49% vs 13% (adjusted difference 33%, 95% credible interval 21–44%, NNT ≈ 2.8).
- Successful reperfusion (mTICI 2b/3): 84%. Median time from symptom onset to groin puncture: 12.2 hours. Median onset-to-reperfusion: 13.6 hours.
- No significant increase in sICH (6% vs 3%, P=0.50) or 90-day mortality (19% vs 18%, P=1.00).
- 53% of patients presented with wake-up stroke — DAWN validated treatment of wake-up strokes using perfusion mismatch selection.
- Results, together with DEFUSE 3, led to AHA/ASA 2018 guideline update extending thrombectomy window to 24 hours for selected patients.
Study Design
- Study Type
- Randomized controlled trial
- Randomization
- Yes
- Blinding
- Blinded endpoint assessment
- Sample Size
- 206
- Follow-up
- 90 days
- Centers
- 26
- Countries
- USA, Canada, Europe, Australia
Primary Outcome
Definition: Utility-weighted modified Rankin Scale at 90 days
| Control | Intervention | HR/OR | P-value |
|---|---|---|---|
| 3.4 | 5.5 | - (1.1–3.0) | <0.001 |
Limitations & Criticisms
- Imbalance in baseline atrial fibrillation (43% control vs 36% intervention) may have biased results — AF associated with larger infarcts and worse outcomes.
- Strict exclusion of large ischemic cores (>51 mL) limits generalizability — later addressed by SELECT2, ANGEL-ASPECT, and RESCUE-Japan LIMIT.
- RAPID perfusion imaging software required — not universally available, particularly in lower-resource settings.
- Industry-sponsored (Stryker) — may influence device selection and reporting.
- Only 5% received IV tPA (due to late presentation) — limited data on combined IV tPA + late-window thrombectomy.
- Stopped early after 206 of 500 planned patients — may overestimate treatment effect.
- Bayesian adaptive design is complex and less intuitive than traditional frequentist analysis.
- Posterior circulation occlusions were excluded — DAWN results cannot be extrapolated to basilar artery occlusion.
Citation
N Engl J Med 2018;378:11–21