BASICS
Endovascular Therapy for Stroke Due to Basilar-Artery Occlusion
Year of Publication: 2021
Authors: Lucianne C.M. Langezaal, Erik J.R.J. van der Hoeven, Francisco J.A. Mont'Alverne, ..., for the BASICS Study Group
Journal: The New England Journal of Medicine
Citation: N Engl J Med 2021;384:1910-20.
PDF: Clinical Question
In patients with acute stroke caused by basilar-artery occlusion, does endovascular therapy initiated within 6 hours of estimated stroke onset improve functional outcomes compared with standard medical care?
Bottom Line
Endovascular therapy did not significantly improve favorable functional outcomes (mRS 0-3) compared with medical therapy in basilar-artery occlusion (44.2% vs 37.7%; RR 1.18; 95% CI 0.92-1.50; P=0.19). Sample size was revised downward from an initial 750 to 300 patients due to slow enrollment over 8 years; the wide CI could not exclude a 10 percentage-point benefit, though a 16 percentage-point benefit was excluded under the revised assumptions. sICH was 4.5% vs 0.7% (P=0.06).
Major Points
- No significant benefit of EVT: favorable outcome (mRS 0-3) was 44.2% (EVT) vs 37.7% (medical), RR 1.18 (95% CI 0.92-1.50; P=0.19), a 6.5 percentage-point difference.
- Sample-size target was revised from the original 750 down to 300 patients due to slow enrollment; the final 300 patients were accrued over 8 years across 23 centers in 7 countries.
- Borderline higher sICH with EVT: 4.5% vs 0.7% (RR 6.9; 95% CI 0.9-53.0; P=0.06).
- No mortality difference: 38.3% (EVT) vs 43.2% (medical) (RR 0.87; 95% CI 0.68-1.12; P=0.29).
- EVT improved vessel recanalization: basilar patency at 24h was 84.5% vs 56.3% (RR 1.43; 95% CI 1.18-1.74). No formal significance testing was done for secondary outcomes (no prespecified plan for multiple-comparison adjustment).
- Moderate-severity NIHSS 10-19 showed signal of benefit: RR 1.55 (95% CI 1.06-2.27); 74% vs 47% favorable. Mild NIHSS <10 trended toward better with medical care (65% vs 80%).
- High IV tPA rate in both arms (~79%) likely contributed to 56.3% spontaneous recanalization, reducing incremental EVT benefit.
- Successful reperfusion (mTICI 2b/3) only 72% despite 94% use of 2nd/3rd-generation devices.
- Malignant brain edema numerically more with EVT: 11.0% vs 4.8% (RR 2.31; 95% CI 0.95-5.62; P=0.06).
- Results could not exclude a clinically meaningful benefit under the original 10 percentage-point assumption (upper CI of RR 1.50), but a 16 percentage-point benefit was excluded under the revised assumptions. Set the stage for BAOCHE.
Design
Study Type: Multicenter, open-label, international, randomized, controlled trial with blinded outcome assessment (PROBE design)
Randomization: 1
Blinding: Open-label treatment; blinded outcome assessment for mRS; independent imaging core lab of 6 neuroradiologists. Permuted blocks (size 2), stratified by center, IV tPA use, and NIHSS (<20 or ≥20).
Enrollment Period: October 23, 2011 to December 6, 2019 (~8 years)
Follow-up Duration: 90 days (no patients lost to follow-up)
Centers: 23
Countries: Netherlands, Brazil, Germany, France, Italy, Switzerland, United States
Sample Size: 300
Analysis: Intention-to-treat (primary); also on-treatment and as-treated analyses.
Inclusion Criteria
- Initial criteria (first 91 patients): age <85 years, NIHSS ≥10.
- Expanded criteria (after 91 patients): age ≥85 allowed, NIHSS <10 allowed, contraindications to IV tPA allowed.
- Acute symptoms and signs compatible with ischemia in the basilar-artery territory.
- Proven basilar-artery occlusion on CTA or MRA (complete obstruction of flow in any portion).
- Endovascular therapy feasible within 6 hours of estimated stroke onset.
- IV thrombolysis (if given) initiated within 4.5 hours of estimated occlusion.
Exclusion Criteria
- Intracranial hemorrhage.
- Extensive, bilateral brainstem infarction on CT.
- Cerebellar mass effect.
- Acute hydrocephalus on neuroimaging.
- Endovascular therapy not feasible within 6 hours of estimated stroke onset.
Baseline Characteristics
| Characteristic | Endovascular Therapy (N=154) | Medical Care (N=146) |
|---|---|---|
| Age (mean±SD) | 66.8±13.1 | 67.2±11.9 |
| Female sex | 54 (35.1%) | 50 (34.2%) |
| Mean NIHSS | 21.9 | 22.1 |
| Median NIHSS | 21 | 22 |
| Hypertension | 93/154 (60.4%) | 82/145 (56.6%) |
| Diabetes mellitus | 34/153 (22.2%) | 31/146 (21.2%) |
| Atrial fibrillation | 44/154 (28.6%) | 22/146 (15.1%) |
| Posterior-circulation stroke history | 11/154 (7.1%) | 7/146 (4.8%) |
| Pre-stroke mRS 0 | 123/153 (80.4%) | 112/146 (76.7%) |
| Pre-stroke mRS 1 | 12/153 (7.8%) | 15/146 (10.3%) |
| Pre-stroke mRS 2 | 15/153 (9.8%) | 17/146 (11.6%) |
| Pre-stroke mRS 3 | 3/153 (2.0%) | 2/146 (1.4%) |
| IV thrombolysis received | 121 (78.6%) | 116 (79.5%) |
| Time onset to IV tPA (median) | 2.0h (IQR 1.4-3.3) | 2.3h (IQR 1.6-3.5) |
| Time onset to EVT (median) | 4.4h (IQR 3.3-6.2) | |
| mTICI 2b/3 reperfusion | 63/88 (72%) |
Arms
| Field | Endovascular Therapy + Medical Care | Control |
|---|---|---|
| Intervention | Endovascular thrombectomy using methods and devices per local operator (94% used 2nd/3rd-generation devices). Angioplasty/stenting of vertebral artery allowed if stenosis hampered access. Basilar stenting allowed for residual stenosis after thrombectomy. Goal: visible outflow in at least one posterior cerebral artery. IV thrombolysis also given in 78.6%. EVT initiated at median 4.4h (IQR 3.3-6.2) after onset. | Conventional care per local protocols and national guidelines, including IV thrombolysis in 79.5%. IV tPA initiated at median 2.3h (IQR 1.6-3.5) after onset. 7 patients (4.8%) crossed over to EVT. |
| Duration | Single procedure + 90 days follow-up | 90 days follow-up |
Outcomes
| Outcome | Type | Control | Intervention | HR / OR / RR | P-value |
|---|---|---|---|---|---|
| mRS 0-3 at 90 days | Primary | 55/146 (37.7%) | 68/154 (44.2%) | 6.48% | 0.19 |
| mRS 0 | Secondary | 6 (4.1%) | 8 (5.2%) | RR 1.17 | |
| mRS 0-1 | Secondary | 19 (13.0%) | 27 (17.5%) | RR 1.32 | |
| mRS 0-2 | Secondary | 44 (30.1%) | 54 (35.1%) | RR 1.17 | |
| mRS 0-4 | Secondary | 71 (48.6%) | 78 (50.6%) | RR 1.05 | |
| mRS 0-5 | Secondary | 83 (56.8%) | 95 (61.7%) | RR 1.09 | |
| Basilar patency at 24h CTA | Secondary | 54/96 (56.3%) | 93/110 (84.5%) | RR 1.43 | |
| Median NIHSS at 24h (IQR) | Secondary | 15.0 (5.0-36.5) | 11.0 (3.0-37.5) | Mean diff -0.79 | |
| EQ-5D VAS at 90 days (mean±SD) | Secondary | 61.9±24.8 | 67.6±21.3 | Mean diff 6.0 | |
| EQ-5D index value at 90 days (mean±SD) | Secondary | 0.61±0.32 | 0.65±0.32 | Mean diff 0.05 | |
| PC-ASPECTS on noncontrast CT at 24h (median) | Secondary | 8.0 (6.0-9.0) | 8.0 (6.0-9.0) | Mean diff -0.03 | |
| PC-ASPECTS on CT angiography at 24h (median) | Secondary | 9.0 (7.0-10.0) | 9.0 (8.0-10.0) | Mean diff 0.32 | |
| Death at 90 days | Adverse | 63 (43.2%) | 59 (38.3%) | RR 0.87 | 0.29 |
| Serious adverse events - 0 | Adverse | 95 (65.1%) | 82 (53.2%) | ||
| Serious adverse events - 1 | Adverse | 33 (22.6%) | 48 (31.2%) | ||
| Serious adverse events - >1 | Adverse | 18 (12.3%) | 24 (15.6%) | ||
| sICH within 3 days | Adverse | 1 (0.7%) | 7 (4.5%) | RR 6.9 | 0.06 |
| Parenchymal hemorrhage Type 1 on 24h CT | Adverse | 4/115 (3.5%) | 2/129 (1.6%) | ||
| Parenchymal hemorrhage Type 2 on 24h CT | Adverse | 1/115 (0.9%) | 6/129 (4.7%) | ||
| Subarachnoid hemorrhage | Adverse | 1/115 (0.9%) | 3/129 (2.3%) | ||
| Subdural hemorrhage | Adverse | 1/115 (0.9%) | 0 | ||
| Intraventricular hemorrhage | Adverse | 0 | 1/129 (0.8%) | ||
| Malignant brain edema | Adverse | 7 (4.8%) | 17 (11.0%) | RR 2.31 | 0.06 |
| Cardiac ischemia | Adverse | 2 (1.4%) | 3 (1.9%) | ||
| Cerebral ischemia | Adverse | 10 (6.8%) | 13 (8.4%) | ||
| Pneumonia | Adverse | 26 (17.8%) | 30 (19.5%) | ||
| Other infection | Adverse | 6 (4.1%) | 7 (4.5%) | ||
| Extracranial hemorrhage | Adverse | 2 (1.4%) | 5 (3.2%) | ||
| Procedural complication | Adverse | 0 | 5 (3.2%) | ||
| Other complication | Adverse | 25 (17.1%) | 20 (13.0%) |
Subgroup Analysis
Prespecified but underpowered; no interaction p-values reported. Key subgroups: NIHSS <10: RR 0.85 (0.62-1.16, favoring medical); NIHSS 10-19: RR 1.55 (1.06-2.27, favoring EVT); NIHSS ≥20: RR 1.28 (0.67-2.46). By location: proximal RR 1.59, middle RR 1.24, distal RR 0.98. Age <70: RR 1.03; ≥70: RR 1.47. Thrombus ≤10mm: RR 1.04; >10mm: RR 1.31. PC-ASPECTS <8: RR 1.08; ≥8: RR 1.16.
Criticisms
- Underpowered relative to original plan: enrollment target was revised downward from 750 to 300 patients due to slow accrual over 8 years; wide CI does not exclude a 10 percentage-point benefit (though the revised 16 percentage-point threshold was excluded).
- 29.2% of eligible patients (124/424) treated outside trial; 79% of those received EVT — equipoise lacking among treating physicians.
- AF imbalance: 28.6% EVT vs 15.1% medical (adjustment did not substantially change results).
- Crossover: 4.8% of medical patients received EVT.
- No advanced imaging (CT perfusion) for patient selection.
- NIHSS less sensitive for posterior circulation symptoms.
- 8-year enrollment span — device technology and medical care evolved significantly.
- High IV tPA rate (~79%) in both arms may have attenuated the treatment effect.
- Successful reperfusion only 72% — lower than anterior circulation trials.
- Open-label design, though outcome assessment was blinded.
Funding
Dutch Heart Foundation, Swiss Heart Foundation, São Paulo Research Foundation, National Council for Scientific and Technological Development (Brazil), University Medical Center Utrecht, St. Antonius Hospital Nieuwegein.
Based on: BASICS (The New England Journal of Medicine, 2021)
Authors: Lucianne C.M. Langezaal, Erik J.R.J. van der Hoeven, Francisco J.A. Mont'Alverne, ..., for the BASICS Study Group
Citation: N Engl J Med 2021;384:1910-20.
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