What are the treatment implications of the Dawn trial?

DAWN Trial Treatment Implications

The DAWN trial established that endovascular thrombectomy (EVT) should be performed in carefully selected acute ischemic stroke patients presenting 6-24 hours after last known well, specifically those with large vessel occlusion and favorable clinical-core mismatch profiles, as this significantly improves functional outcomes and reduces mortality. 1

Patient Selection Criteria from DAWN

The DAWN trial defined specific imaging and clinical criteria that now guide late-window thrombectomy decisions 1:

• NIHSS ≥10 with core infarct 0-21 mL (for patients >80 years old) 1
• NIHSS ≥10 with core infarct 0-31 mL (for patients <80 years old) 1
• NIHSS ≥20 with core infarct 31 to <51 mL (for patients <80 years old) 1

These criteria represent clinical-core mismatch—where the severity of neurological deficit substantially exceeds the volume of irreversibly injured brain tissue, indicating substantial salvageable penumbra 1.

Required Imaging Infrastructure

Sites must have specific imaging capabilities to implement DAWN criteria 1:

• CT perfusion (CTP) imaging with software providing reproducible objective measurements of ischemic core and penumbra 1
• CT angiography (CTA) from ascending aorta to vertex to identify proximal intracranial artery occlusion (carotid artery, M1 segment of MCA, or proximal M2 divisions) amenable to EVT 1
• 24-hour, seven-day-per-week access to stroke imaging 1

Clinical Implementation Algorithm

For patients presenting 6-24 hours from last known well 1:

1. Confirm proximal anterior circulation large vessel occlusion on CTA 1
2. Measure ischemic core volume using CTP (areas of low cerebral blood volume or cerebral blood flow) 1
3. Apply age-stratified DAWN criteria matching NIHSS score to core volume thresholds 1
4. Proceed to EVT if criteria met, as this provides Class 1A recommendation 2

Expanded Treatment Window Impact

The DAWN trial fundamentally changed stroke care by demonstrating that time-based exclusion alone is insufficient—tissue-based selection identifies patients who benefit from thrombectomy up to 24 hours after onset 3, 2. This represents a paradigm shift from "time is brain" to "tissue is brain" for carefully selected patients 3.

Comparison with DEFUSE-3 Criteria

While DAWN uses clinical-core mismatch, DEFUSE-3 uses different criteria (core <70 mL, mismatch ratio ≥1.8, mismatch volume ≥15 mL) 1. DEFUSE-3 is more inclusive and captures additional patients who benefit from late-window thrombectomy 4. Patients meeting DEFUSE-3 but not DAWN criteria—particularly those with cores between 51-70 mL—still demonstrate benefit from EVT 4.

Outcomes and Treatment Effect

The DAWN trial showed strong treatment effect with number needed to treat ranging from 3-10 2. Successful recanalization is significantly associated with favorable clinical outcomes (modified Rankin Scale 0-2) and reduced mortality 1, 3.

Critical Caveats

• Core volume estimation must be accurate—combining CTP volumes with any additional hypodensity on non-contrast CT not visualized on CTP 1
• Moderate-to-good pial collateral filling on CTA or CTP mismatch predicts better response to EVT 1
• Rapid treatment remains critical even in the extended window—every minute of delay reduces probability of good outcome 3
• Symptomatic intracranial hemorrhage risk must be monitored, though rates remain acceptable (approximately 6-10%) 5, 6

Systems of Care Requirements

Implementing DAWN criteria requires comprehensive stroke systems with immediate access to advanced imaging, interventional neuroradiology teams, and intensive care unit monitoring 1, 3. The 2018 Canadian Stroke Best Practice Recommendations incorporated these requirements as standard of care 1.