What are the guidelines for endovascular therapy in acute ischemic stroke based on the DEFUSE (Diffusion-Weighted Imaging Evaluation for Understanding Stroke Evolution) trial?

Guidelines for Endovascular Therapy in Acute Ischemic Stroke Based on DEFUSE Trial

Endovascular thrombectomy is strongly recommended for patients with acute ischemic stroke due to large vessel occlusion in the 6-16 hour time window who meet DEFUSE 3 criteria, with treatment resulting in significantly better functional outcomes compared to standard medical therapy alone. 1

Patient Selection Criteria for Extended Time Window (6-16 hours)

DEFUSE 3 Trial Criteria

• Proximal middle cerebral artery (M1) or internal carotid artery (ICA) occlusion 2, 1
• Initial infarct size <70 ml 1
• Ratio of ischemic tissue volume to infarct volume ≥1.8 1
• Patient last known well between 6-16 hours prior to treatment 1

Additional Selection Factors

• Age ≥18 years 2, 3
• Pre-stroke modified Rankin Scale (mRS) score of 0-1 2, 3
• NIHSS score ≥6 2
• ASPECTS ≥6 2, 3

Imaging Protocol for Patient Selection

1. Initial Imaging:

   • Non-contrast CT (NCCT) to rule out hemorrhage and estimate ischemic core using ASPECTS 2
   • CT angiography (CTA) or multiphase CTA (mCTA) to detect and localize the occlusion 2

2. Advanced Imaging for Extended Window:

   • CT perfusion (CTP) or diffusion-weighted MRI to determine ischemic core volume 2
   • Perfusion imaging to identify salvageable tissue (penumbra) 2, 1

Current guidelines recommend CTP or DWI in patients with unknown onset and those presenting >6 hours from onset because the DEFUSE-3 trial relied on these modalities to determine ischemic core and identify patients with salvageable tissue 2.

Treatment Recommendations

1. Early Window (0-6 hours):

   • Patients should receive IV thrombolysis if eligible 2
   • Proceed directly to endovascular therapy without waiting to assess response to IV thrombolysis 2
   • CTP is not necessary for clinical decision-making in this time window 2

2. Extended Window (6-16 hours):

   • Patients meeting DEFUSE 3 criteria should receive endovascular thrombectomy 1
   • Treatment results in better functional outcomes than standard medical therapy alone 1
   • The goal should be achieving modified TICI grade 2b/3 reperfusion 2, 4

3. Very Extended Window (16-24 hours):

   • Patients meeting DAWN criteria may receive endovascular thrombectomy 3
   • Beyond 24 hours, treatment is not currently recommended 3

Clinical Outcomes Based on DEFUSE 3

• Functional Independence: 45% of thrombectomy patients achieved functional independence (mRS 0-2) at 90 days versus 17% with medical therapy alone 1
• Mortality: 14% in thrombectomy group versus 26% in medical therapy group 1
• Hospital Stay: Median length of hospital stay was 6.5 days in thrombectomy group versus 9.1 days in medical therapy group 5
• Home Time: Median home-time during first 90 days was 55 days in thrombectomy group versus 0 days in medical therapy group 5

Technical Considerations

• Stent retrievers are preferred over other mechanical thrombectomy devices 2, 3
• Using a proximal balloon guide catheter or large-bore distal-access catheter may be beneficial 2
• Complete reperfusion (TICI 3) results in better outcomes than partial reperfusion (TICI 2B) 4
• Successful reperfusion is independent of device used, site of occlusion, or adjunctive use of carotid angioplasty and stenting 4

Important Caveats

1. Persistent Mismatch Beyond 24 Hours:

   • Approximately 20% of untreated patients maintain a favorable perfusion profile beyond 24 hours 6
   • These patients have favorable collaterals (lower hypoperfusion intensity ratio) but still experience poor clinical outcomes without treatment 6

2. Penumbra Salvage:

   • In untreated patients, approximately 54% of Tmax >6s penumbral tissue is consumed within 24 hours 7
   • With successful reperfusion (TICI 3), only about 5% of Tmax >6s penumbral tissue is consumed 7

3. Potential Pitfalls:

   • Overly selective treatment criteria may deny treatment to patients who could benefit 2
   • Many late-window patients with unknown symptom onset (wake-up strokes) might actually be within the 6-hour time window 2
   • Relying solely on time from last known well without considering tissue viability may exclude eligible patients 2

The DEFUSE 3 trial has significantly expanded the treatment window for acute ischemic stroke, demonstrating that with appropriate patient selection using perfusion imaging, endovascular thrombectomy can provide substantial clinical benefits even in the extended time window of 6-16 hours after symptom onset.