PDF: EXTEND-IA
(2015)Objective
To evaluate whether early thrombectomy using Solitaire improves outcomes compared to alteplase alone in patients with LVO and salvageable tissue.
Study Summary
• Thrombectomy with Solitaire after alteplase led to better reperfusion, early neurologic improvement, and improved functional outcomes versus alteplase alone.
Intervention
IV alteplase (0.9 mg/kg) with or without Solitaire thrombectomy. Endovascular therapy started within 6 hours after onset and completed within 8 hours.
Inclusion Criteria
Acute anterior circulation stroke, within 4.5 hours from onset, LVO (ICA/M1/M2), salvageable tissue and ischemic core <70 mL on perfusion imaging, mRS <2 before stroke.
Study Design
Arms: Thrombectomy + Alteplase vs. Alteplase Alone
Patients per Arm: Thrombectomy: 35, Alteplase: 35
Outcome
• Primary: Reperfusion at 24h: median 100% vs. 37%, P<0.001. Early neurologic improvement: 80% vs. 37%, P=0.002.• mRS 0–2 at 90d: 71% vs. 40%, P=0.01.• Median mRS at 90d: 1 vs. 3.• Ordinal mRS shift: Wilcoxon–Mann–Whitney generalized OR 2.0 (95% CI 1.2–3.8), P=0.006.• sICH: 0% vs. 6%.• Mortality: 9% vs. 20% (adjusted P=0.31; unadjusted P=0.18).• Parenchymal hematoma: 11% vs. 9%.• Groin hematoma requiring transfusion in the endovascular group.• Reperfusion >90% at 24h without sICH: 89% vs. 34%, P<0.001.• Median infarct growth: 10.9 vs. 35.3 mL.• Median home time at 90d: 73 vs. 15 days.
Bottom Line
Endovascular thrombectomy with the Solitaire FR device significantly improved early reperfusion, functional outcomes, and reduced infarct growth compared to IV tPA alone in patients with large-vessel occlusion and favorable imaging profile.
Major Points
- One of five landmark 2015 thrombectomy RCTs. Unique contribution: first to use automated CT perfusion (RAPID software) for patient selection and first to demonstrate perfusion imaging-guided thrombectomy efficacy.
- Conducted in Australia and New Zealand (10 enrolling centers) — the only 2015 trial from the Southern Hemisphere.
- Stopped early after just 70 patients (target 100) at the first planned interim analysis — the smallest of the 2015 trials but with the largest effect sizes.
- Coprimary outcomes were reperfusion at 24h on perfusion imaging (100% endovascular vs 37% control, p<0.001) and early neurologic improvement at 3 days (80% vs 37%, p=0.002).
- Functional independence (mRS 0–2 at 90 days): 71% vs 40% (adjusted OR 4.2, 95% CI 1.4–12, p=0.01) — the highest absolute rate of independence in any 2015 thrombectomy trial.
- Median infarct growth at 24h: 10.9 mL endovascular vs 35.3 mL alteplase-only (p=0.007) — demonstrating that thrombectomy substantially reduces infarct progression.
- Pioneered use of RAPID automated perfusion software for patient selection: ischemic core <70 mL, mismatch ratio >1.2. This became the standard imaging paradigm for DAWN, DEFUSE 3, and subsequent trials.
- Occlusion sites eligible: ICA, M1 or M2 segment of MCA. Required IV tPA eligibility (bridging therapy mandatory, similar to SWIFT PRIME).
- 90-day mortality: 9% endovascular vs 20% alteplase-only (adjusted p=0.31; unadjusted p=0.18) — numerically the largest mortality reduction among 2015 trials, though not significant due to small sample size.
- sICH: 0% endovascular vs 6% alteplase-only (p=0.49) — no sICH in the endovascular arm; both sICH events in the control arm were fatal.
- Solitaire FR stent retriever was the exclusive device used — results specific to this device platform.
Study Design
- Study Type
- Prospective, randomized, open-label, blinded endpoint (PROBE) multicenter trial
- Randomization
- Yes
- Blinding
- Outcome assessors were blinded; patients and physicians were unblinded
- Sample Size
- 70
- Follow-up
- 90 days
- Centers
- 10
- Countries
- Australia, New Zealand
Primary Outcome
Definition: Coprimary: (1) Reperfusion at 24 h — percentage reduction in perfusion-lesion volume between baseline and 24-hour imaging; (2) Early neurologic improvement — ≥8-point reduction on NIHSS or NIHSS 0 or 1 at day 3
| Control | Intervention | HR/OR | P-value |
|---|---|---|---|
| Median reperfusion 37% (IQR −0.5 to 96); Early neurologic improvement 13/35 (37%) | Median reperfusion 100% (IQR 100 to 100); Early neurologic improvement 28/35 (80%) | - (Reperfusion Wilcoxon–Mann–Whitney generalized OR 4.7 (2.5–9.0); Early neurologic improvement adjusted OR 6.0 (2.0–18.0)) | <0.001 (reperfusion); 0.002 (early neurologic improvement) |
Limitations & Criticisms
- Smallest of the 2015 thrombectomy trials (n=70) — stopped early at first interim analysis, raising concerns about effect size overestimation (acknowledged by the authors).
- Highly selected population: required CT perfusion with automated RAPID software, IV tPA eligibility, and favorable mismatch profile — may not generalize to patients without perfusion imaging access.
- Open-label design (PROBE) — knowledge of treatment assignment could influence post-procedure care intensity and rehabilitation referral patterns.
- Exclusive use of Solitaire FR device — results cannot be directly extrapolated to aspiration-first techniques or other device platforms.
- Australia/New Zealand healthcare system context — workflow and access patterns may differ from North American and European settings.
- CT perfusion availability required at enrolling sites — limits applicability in settings without 24/7 perfusion imaging capability.
- Mandatory IV tPA excludes patients with contraindications to thrombolysis — later studies (MR CLEAN subgroups) showed benefit of direct thrombectomy.
- Only 10 of 14 planned centers actually enrolled patients — trial recruitment was concentrated in a limited number of high-volume sites.
Citation
N Engl J Med 2015;372:1009–18