PDF: DEFUSE 3
(2018)Objective
To determine whether endovascular thrombectomy is effective 6 to 16 hours after stroke onset in patients with salvageable brain tissue identified using perfusion imaging.
Study Summary
Intervention
Endovascular thrombectomy with FDA-approved devices plus standard medical therapy versus standard medical therapy alone. Imaging selection was based on RAPID software to identify target mismatch (ischemic core <70 mL, mismatch ratio ≥1.8, mismatch volume ≥15 mL).
Inclusion Criteria
Adults with acute ischemic stroke due to ICA or proximal MCA occlusion, 6–16 hours from last known well, with infarct core <70 mL and target mismatch profile on perfusion CT or MRI.
Study Design
Arms: Thrombectomy + Medical Therapy vs. Medical Therapy Alone
Patients per Arm: Thrombectomy: 92, Medical Therapy: 90
Outcome
Bottom Line
In patients with proximal anterior circulation occlusions and salvageable brain tissue on perfusion imaging, endovascular thrombectomy between 6–16 hours from last known well significantly improved functional outcomes and reduced mortality compared to medical therapy alone.
Major Points
- Randomized controlled trial of thrombectomy vs. medical therapy in patients 6–16 hours after last known well with perfusion imaging evidence of salvageable brain tissue (ischemic core <70 mL, mismatch ratio ≥1.8, mismatch volume ≥15 mL assessed by RAPID software).
- Eligible vessels: intracranial ICA or proximal MCA (M1 segment) on CTA or MRA. ICA occlusions were 35% of cohort, M1 MCA 65%.
- Trial stopped early after 182 of planned 476 patients due to overwhelming efficacy at prespecified interim analysis.
- Primary outcome (ordinal mRS shift at 90 days): OR 2.77 (95% CI 1.63–4.70, P<0.001) — thrombectomy shifted the entire mRS distribution favorably.
- Functional independence (mRS 0–2) at 90 days: 45% vs 17% (RR 2.67, P<0.001, NNT ≈ 4).
- Mortality: 14% vs 26% (P=0.05) — trend toward reduced mortality with thrombectomy.
- No significant increase in sICH (7% vs 4%, P=0.75) or serious adverse events (43% vs 53%).
- 53% of patients had wake-up stroke; 75% selected by CT perfusion, 25% by MRI perfusion.
- Median ischemic core volume was 9.4 mL (IQR 2.0–25.6); median perfusion lesion 114.7 mL. Median time from LKW to randomization ~10.9 hours.
- Together with DAWN, led to AHA/ASA 2018 guideline update extending thrombectomy window to 16–24 hours for imaging-selected patients.
Study Design
- Study Type
- Randomized, open-label, blinded-endpoint controlled trial
- Randomization
- Yes
- Blinding
- Blinded outcome assessment
- Sample Size
- 182
- Follow-up
- 90 days
- Centers
- 38
- Countries
- United States
Primary Outcome
Definition: Ordinal shift in mRS at 90 days (0–6 scale), analyzed by ordinal logistic regression
| Control | Intervention | HR/OR | P-value |
|---|---|---|---|
| Median mRS 4 (17% mRS 0–2) | Median mRS 3 (45% mRS 0–2) | - (1.63–4.70) | <0.001 |
Limitations & Criticisms
- Stopped early after 182 of 476 planned patients — may overestimate treatment effect.
- Open-label design may introduce bias despite blinded outcome assessment (PROBE design).
- Generalizability limited to patients with access to RAPID perfusion imaging — not available at many hospitals, especially in lower-resource settings.
- Only U.S. sites enrolled — limited international generalizability.
- Small sample size (182) limits power for subgroup analyses.
- Only 11% received IV tPA — different from early-window practice where >70% receive IV tPA before thrombectomy.
- Posterior circulation excluded — cannot extrapolate to basilar artery occlusions in the late window.
- RAPID software dependency — results may not be reproducible with other automated perfusion platforms.
Citation
N Engl J Med 2018;378:708–18