REVASCAT
Thrombectomy within 8 Hours after Symptom Onset in Ischemic Stroke
Year of Publication: 2015
Authors: T.G. Jovin, A. Chamorro, E. Cobo, ..., and A. Dávalos
Journal: The New England Journal of Medicine
Citation: N Engl J Med 2015;372:2296-306.
PDF: Clinical Question
In patients with acute ischemic stroke due to a proximal anterior circulation occlusion who can be treated within 8 hours of symptom onset, does endovascular therapy with the Solitaire stent retriever improve functional outcomes compared to medical therapy alone?
Study Overview
Objective
To assess the safety and efficacy of stent retriever thrombectomy within 8 hours after stroke onset in patients with anterior circulation LVO.
Study Summary
Thrombectomy using Solitaire within 8 hours improved functional outcomes in anterior circulation stroke compared to medical therapy alone.
Intervention
Solitaire FR thrombectomy device plus standard medical therapy (including alteplase when eligible) vs. standard medical therapy alone. Patients were randomized up to 8 hours from onset.
Patients per Arm
Thrombectomy: 103, Medical Therapy: 103
Bottom Line
Among patients with anterior circulation large-vessel occlusion stroke treatable within 8 hours, endovascular thrombectomy with the Solitaire stent retriever significantly reduced the severity of post-stroke disability and increased the rate of functional independence at 90 days compared with medical therapy alone.
Major Points
- One of five landmark thrombectomy RCTs published in 2015 (MR CLEAN, ESCAPE, EXTEND-IA, SWIFT PRIME, REVASCAT) that collectively established mechanical thrombectomy as standard of care for LVO stroke.
- Conducted at 4 comprehensive stroke centers in Catalonia, Spain — the most geographically concentrated of the 2015 trials.
- Stopped early at 206 patients (target 690) due to loss of equipoise after MR CLEAN, ESCAPE, and EXTEND-IA published positive results.
- Unique 8-hour treatment window — the longest among the 2015 trials (MR CLEAN 6h, ESCAPE 12h, EXTEND-IA 6h, SWIFT PRIME 6h) — providing early evidence for extended time windows.
- Primary outcome: ordinal shift in mRS at 90 days favored thrombectomy (adjusted OR 1.7, 95% CI 1.05–2.8). Functional independence (mRS 0–2): 43.7% vs 28.2%.
- Dramatic early neurologic improvement at 24h (NIHSS drop ≥8 or score 0–2): 59% vs 20% (adjusted OR 5.8, 95% CI 3.0–11.1) — the most striking 24-hour outcome among the 2015 trials.
- Occlusion sites: ICA ~35%, M1 ~65%. Solitaire stent retriever was the exclusive first-line device.
- High IV tPA co-treatment rate: 68–78% received alteplase before randomization.
- No significant difference in sICH (1.9% each group) or 90-day mortality (18.4% vs 15.5%).
- Notably included older patients (age cap initially 80, later amended to 85) and required ASPECTS >6 on CT or >5 on DWI — stricter imaging criteria than MR CLEAN.
Design
Study Type: Multicenter, prospective, randomized, open-label phase 3 study with blinded evaluation of outcomes.
Randomization: 1
Blinding: Open-label for treatment assignment; outcome assessors for the modified Rankin Scale were blinded.
Enrollment Period: November 2012 through December 2014.
Follow-up Duration: 90 days.
Centers: 4
Countries: Spain
Sample Size: 206
Analysis: Intention-to-treat.
Inclusion Criteria
- Age 18 to 80 years (later amended to 85 years).
- Occlusion in the proximal anterior circulation (intracranial internal carotid artery or M1 segment of the middle cerebral artery).
- Could be treated within 8 hours after symptom onset.
- Pre-stroke modified Rankin Scale score of 1 or less.
- Baseline NIHSS score of 6 or more.
- Absence of a large ischemic core on imaging (ASPECTS >6 on CT or >5 on DWI).
Exclusion Criteria
- Large infarct core on imaging (ASPECTS ≤6 on CT or ≤5 on DWI-MRI).
- Prestroke modified Rankin Scale score >1 (pre-existing significant disability).
- NIHSS <6 (mild stroke).
- No confirmed proximal anterior circulation occlusion on CTA/MRA.
- Rapidly improving neurological symptoms.
- Known hemorrhagic diathesis or coagulopathy.
- Baseline blood glucose <50 mg/dL.
- Severe contrast allergy or renal insufficiency.
- Life expectancy <6 months from pre-existing condition.
- Pregnancy.
- Participation in another clinical trial.
Baseline Characteristics
| Characteristic | Control | Active |
|---|---|---|
| Mean age ±SD - yr | 67.2±9.5 | 65.7±11.3 |
| Male sex - no. (%) | 54 (52.4) | 55 (53.4) |
| Atrial fibrillation - no. (%) | 37 (35.9) | 35 (34.0) |
| Hypertension - no. (%) | 72 (69.9) | 62 (60.2) |
| Diabetes mellitus - no. (%) | 21 (20.4) | 18 (17.5) |
| Dyslipidemia - no. (%) | 41 (39.8) | 39 (37.9) |
| Current smoker - no. (%) | 26 (25.2) | 29 (28.2) |
| Prior stroke - no. (%) | 10 (9.7) | 9 (8.7) |
| Median NIHSS score (IQR) | 17.0 (12.0-19.0) | 17.0 (14.0-20.0) |
| Treatment with intravenous alteplase - no. (%) | 80 (77.7) | 70 (68.0) |
| Median ASPECTS value (IQR) | 8.0 (6.0-9.0) | 7.0 (6.0-9.0) |
| Occlusion site - ICA - no./total no. (%) | 36/101 (35.6) | 36/102 (35.3) |
| Occlusion site - M1 - no./total no. (%) | 65/101 (64.4) | 66/102 (64.7) |
| Median time from onset to randomization (IQR) - min | 269 (192–349) | 282 (196–362) |
Arms
| Field | Control | Thrombectomy + Medical Therapy |
|---|---|---|
| Intervention | Standard medical therapy including IV alteplase (0.9 mg/kg, max 90 mg) if eligible within 4.5h of onset. Antiplatelet agents, antihypertensives, statins, and DVT prophylaxis per local protocols. IV alteplase was given to 77.7% of control patients. No endovascular intervention permitted. | Endovascular thrombectomy using Solitaire FR or Solitaire 2 stent retriever as the mandated first-line device. Up to 6 passes allowed. Conscious sedation or general anesthesia at operator discretion. Rescue therapy with other devices permitted if Solitaire failed. Intra-arterial tPA not permitted. Balloon guide catheters used in most cases. Target: groin puncture within 30 minutes of randomization. All patients also received standard medical therapy including IV alteplase if eligible (68% received it). |
| Duration | 90 days | 90 days |
Outcomes
| Outcome | Type | Control | Intervention | HR / OR / RR | P-value |
|---|---|---|---|---|---|
| The severity of global disability at 90 days, assessed by the distribution of scores on the modified Rankin scale (analyzed as an ordinal shift). | Primary | 1.7 | |||
| Functional independence (mRS 0-2) at 90 days | Secondary | 28.2% (29/103) | 43.7% (45/103) | Adjusted OR 2.1 (95% CI, 1.1 to 4.0) | |
| Dramatic neurologic improvement at 24 hr (NIHSS decrease ≥8 or score 0-2) | Secondary | 20.0% (20/100) | 59.0% (59/100) | Adjusted OR 5.8 (95% CI, 3.0 to 11.1) | |
| Death at 90 days | Adverse | 15.5% (16/103) | 18.4% (19/103) | Risk Ratio 1.2 (95% CI, 0.6 to 2.2) | 0.60 |
| Symptomatic intracranial hemorrhage (SITS-MOST criteria) at 90 days | Adverse | 1.9% (2/103) | 1.9% (2/103) | 1.00 |
Subgroup Analysis
Benefit was consistent across prespecified subgroups (age <70 vs ≥70, NIHSS <17 vs ≥17, ICA vs M1 occlusion, ASPECTS ≤7 vs >7, time to randomization <4.5h vs ≥4.5h). Notably, treatment effect persisted in the 4.5–8 hour subgroup (aOR 1.3), providing early evidence for extended window thrombectomy. Patients receiving IV tPA benefited similarly to those not receiving it. The 8-hour window subgroup data helped inform DAWN and DEFUSE 3 trial designs. Trial was underpowered for formal interaction testing.
Criticisms
- Stopped early at 206/690 patients (30%) — markedly underpowered for subgroup analyses and rare event detection.
- Conducted at only 4 highly experienced centers in Catalonia, Spain — among the most geographically restricted of the 2015 thrombectomy trials, limiting generalizability.
- Protocol mandated vessel occlusion confirmation 30 minutes after alteplase administration, potentially delaying thrombectomy in bridging therapy patients.
- Discrepancies between site and core lab ASPECTS readings — some patients had ASPECTS ≤6 on core lab review but were enrolled based on site interpretation.
- Used ASPECTS on NCCT/DWI rather than advanced perfusion imaging (unlike EXTEND-IA and SWIFT PRIME), potentially including patients with larger established infarcts.
- Open-label treatment assignment with potential for bias in post-stroke care intensity, partially mitigated by blinded outcome assessment.
- Solitaire was mandated as first-line device — results may not generalize to other stent retriever or aspiration-first approaches.
- Higher mortality in thrombectomy group (18.4% vs 15.5%), though not significant — raises questions about safety in this extended-window population.
Funding
Fundació Ictus Malaltia Vascular through an unrestricted grant from Covidien and others.
Based on: REVASCAT (The New England Journal of Medicine, 2015)
Authors: T.G. Jovin, A. Chamorro, E. Cobo, ..., and A. Dávalos
Citation: N Engl J Med 2015;372:2296-306.
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