What are the outcomes for thrombectomy in extended time windows using perfusion scanning for acute ischemic stroke patients?

Thrombectomy in Extended Time Windows Using Perfusion Imaging: Outcomes

Thrombectomy in extended time windows (6-24 hours) using perfusion imaging for patient selection produces excellent functional outcomes, with 45-49% of patients achieving functional independence compared to 13-17% with medical therapy alone, representing a number needed to treat of less than 2.

Evidence for Extended Window Thrombectomy

The Paradigm Shift: Tissue Window vs. Time Window

Perfusion imaging enables identification of salvageable brain tissue (the ischemic penumbra) beyond arbitrary time cutoffs, fundamentally changing patient selection from time-based to tissue-based criteria 1, 2. This represents the most significant advancement in acute stroke treatment, as time of ischemia is only an average biomarker for tissue viability—individual patients vary dramatically based on collateral flow adequacy 2.

Landmark Trial Outcomes

The two pivotal trials that established extended window thrombectomy demonstrate remarkable efficacy:

• DAWN trial (6-24 hours, median 12.5 hours): Patients selected by clinical-imaging mismatch showed a 35.5% absolute increase in functional independence—the largest effect ever described in any acute stroke treatment trial 2.

• DEFUSE-3 trial (6-16 hours, median 11 hours): Thrombectomy resulted in 45% functional independence versus 17% with medical therapy alone (P<0.001), with 28% absolute increase in functional independence and 20% absolute reduction in death or severe disability 3, 2.

Selection Criteria Using Perfusion Imaging

The key to success in extended windows is rigorous patient selection using perfusion imaging to identify salvageable tissue 1, 4:

• Core-penumbra mismatch: Ratio of ischemic tissue volume to infarct volume ≥1.8 3
• Small infarct core: Initial infarct size <70 ml on CT perfusion or DWI-MRI 3, 5
• Large vessel occlusion: Proximal middle cerebral artery or internal carotid artery occlusion 3, 5
• Salvageable penumbra: Documented perfusion-core mismatch on CTP or DW-MRI 1, 4

Comparative Effectiveness

The number needed to treat with thrombectomy in extended windows is extraordinarily low:

• Extended window (6-24 hours) with perfusion selection: NNT <2 for functional independence 6
• Standard window (<6 hours): NNT 2.6 for one-level improvement on modified Rankin Scale 2

This means perfusion-selected patients in extended windows actually have BETTER treatment effects than unselected early-window patients 6.

Imaging Requirements and Techniques

Perfusion Imaging Modalities

Either CT perfusion or MR perfusion can effectively identify salvageable tissue, though the specific technique matters less than proper patient selection 7, 4:

• CT perfusion: Differentiates infarcted core from salvageable penumbra, essential for selecting patients beyond 6 hours 4
• MR diffusion/perfusion mismatch: Qualitative marker for potential infarct expansion, used successfully in DIAS trial up to 9 hours 7
• Vascular imaging: CTA, MRA, or DSA must accompany perfusion imaging to confirm large vessel occlusion 4

Critical Imaging Pitfalls

The most dangerous error is performing only non-contrast CT without vascular imaging, which misses large vessel occlusions requiring endovascular therapy 4. For any patient being considered for thrombectomy beyond 6 hours, multimodal imaging with perfusion assessment is essential 4.

Safety Profile in Extended Windows

Thrombectomy in extended windows with perfusion selection maintains excellent safety 3:

• Symptomatic intracranial hemorrhage: 7% (thrombectomy) vs 4% (medical therapy), not statistically significant 3
• 90-day mortality: 14% (thrombectomy) vs 26% (medical therapy), P=0.05 3
• No significant difference in serious adverse events 3

Time-Dependent Considerations

Every hour of delay reduces the likelihood of good functional outcomes, even within the extended window 1. The American Heart Association explicitly states that observation after IV alteplase to assess clinical response before pursuing thrombectomy is contraindicated (Class III: Harm) because any delay worsens outcomes 1.

Practical Algorithm

1. 6-24 hours from last known well: Obtain CT perfusion or MR perfusion immediately 1, 4
2. Confirm large vessel occlusion: Use CTA, MRA, or proceed directly to angiography 4
3. Assess core size: Must be <70 ml on perfusion imaging 3
4. Calculate mismatch ratio: Perfusion lesion to core ratio ≥1.8 3
5. Proceed to thrombectomy immediately if criteria met—do not delay 1

Limitations and Nuances

While perfusion imaging has revolutionized extended window treatment, important caveats exist:

• MR perfusion specificity: MRP overestimates final infarct volume in most cases, making it highly sensitive but less specific for predicting tissue outcome 7
• Quantification challenges: True quantification of penumbra remains difficult, though qualitative mismatch has proven clinically useful 7
• Validation status: The mismatch concept, while supported by multiple phase II trials, required the DAWN and DEFUSE-3 trials to provide definitive level A evidence 7, 2

The evidence demonstrates that perfusion imaging enables safe and highly effective thrombectomy up to 24 hours after stroke onset, with outcomes superior to standard time-window treatment when patients are properly selected based on tissue viability rather than time alone 2, 3, 6.