Interventional Radiology · Neurointervention · Primary publication

DEFUSE 3 (2018): Perfusion-Selected Thrombectomy at 6–16 Hours

DEFUSE 3 established the benefit of mechanical thrombectomy 6–16 hours after last known well in selected anterior-circulation large-vessel occlusion with a favourable perfusion-mismatch profile.

Key takeaway

In carefully selected patients with anterior-circulation large-vessel occlusion and salvageable tissue on automated CT or MR perfusion imaging, thrombectomy performed 6–16 hours after last known well substantially improved 90-day functional outcome compared with medical therapy alone.

At a glance

Study design: Multicentre, prospective, randomised, open-label, blinded-endpoint trial conducted at 38 US centres. Patients were assigned 1:1 to thrombectomy plus standard medical therapy or standard medical therapy alone; the trial was terminated early for efficacy after an interim analysis prompted by the DAWN results.
Population: Patients aged 18–90 years with acute anterior-circulation ischaemic stroke, NIHSS score of at least 6, pre-stroke modified Rankin Scale score of 0–2, cervical or intracranial internal carotid artery or proximal M1 middle cerebral artery occlusion, and an automated target-mismatch profile comprising an ischaemic core below 70 mL, mismatch ratio of at least 1.8 and mismatch volume of at least 15 mL. Endovascular treatment had to be initiated 6–16 hours after last known well.
Sample size: 182 participants
Intervention: Mechanical thrombectomy with an FDA-cleared thrombectomy device plus standard medical therapy.
Comparator: Standard medical therapy alone.
Primary endpoint: Ordinal distribution of modified Rankin Scale scores at 90 days.

Key results

The 90-day modified Rankin Scale distribution favoured thrombectomy: median score 3 versus 4, with an unadjusted common odds ratio of 2.77 (95% CI 1.63–4.70; P<0.001).
Functional independence at 90 days, defined as modified Rankin Scale 0–2, occurred in 45% with thrombectomy versus 17% with medical therapy (risk ratio 2.67, 95% CI 1.60–4.48; P<0.001).
Mortality at 90 days was 14% with thrombectomy versus 26% with medical therapy (P=0.05).
Symptomatic intracranial haemorrhage occurred in 7% with thrombectomy and 4% with medical therapy; the difference was not statistically significant (P=0.75).

Limitations

The trial was stopped early after 182 of a planned maximum of 476 participants had been randomised, reducing precision for safety and subgroup analyses.
Only highly selected patients with a small infarct core and favourable automated perfusion-mismatch profile were enrolled, limiting generalisability to patients with larger cores or absent mismatch.
Advanced CT perfusion or MR diffusion-perfusion imaging with RAPID processing was required, so the results cannot automatically be extrapolated to different selection methods.
Treatment allocation could not be blinded, although 90-day outcomes were assessed by certified assessors intended to be unaware of treatment assignment.

Why it matters

DEFUSE 3 demonstrated that tissue viability, rather than clock time alone, can identify patients who benefit from thrombectomy beyond 6 hours. Together with DAWN, it established late-window thrombectomy as a major treatment pathway for selected anterior-circulation large-vessel occlusion.

Practice implication

Patients presenting 6–16 hours after last known well should not be excluded from thrombectomy solely because of elapsed time when CTA or MRA confirms an eligible anterior-circulation occlusion and automated perfusion imaging demonstrates the DEFUSE 3 target-mismatch profile.

Exam pearl

Remember the DEFUSE 3 imaging triad: ischaemic core below 70 mL, mismatch ratio at least 1.8 and mismatch volume at least 15 mL, with thrombectomy initiated within 6–16 hours of last known well.

Viva questions

What is the full form of DEFUSE 3?: DEFUSE 3 stands for Endovascular Therapy Following Imaging Evaluation for Ischemic Stroke 3.
What was the design of DEFUSE 3?: It was a multicentre, randomised, open-label trial with blinded 90-day outcome assessment, comparing thrombectomy plus medical therapy with medical therapy alone at 38 US centres.
Which vascular occlusions were eligible for DEFUSE 3?: CTA or MRA had to demonstrate cervical or intracranial internal carotid artery occlusion or proximal M1 middle cerebral artery occlusion.
What was the DEFUSE 3 target-mismatch profile?: The ischaemic core had to be below 70 mL, the mismatch ratio at least 1.8 and the mismatch volume at least 15 mL on automated CT perfusion or MR diffusion-perfusion analysis.
What was the primary endpoint and result of DEFUSE 3?: The primary endpoint was the ordinal 90-day modified Rankin Scale distribution. It favoured thrombectomy with a common odds ratio of 2.77 and P<0.001.
What was the functional-independence result in DEFUSE 3?: At 90 days, modified Rankin Scale 0–2 was achieved in 45% with thrombectomy versus 17% with medical therapy alone.
What were the major safety results of DEFUSE 3?: Ninety-day mortality was 14% versus 26%, while symptomatic intracranial haemorrhage was 7% versus 4% and was not significantly different.
How should DEFUSE 3 be distinguished from DAWN?: DEFUSE 3 selected patients within 6–16 hours using a tissue–core perfusion mismatch, whereas DAWN extended selection to 24 hours and used an age-adjusted clinical–core mismatch.