BASIS
(2024)Objective
To determine whether submaximal balloon angioplasty plus aggressive medical management is superior to aggressive medical management alone for secondary stroke prevention in patients with symptomatic intracranial atherosclerotic stenosis (70–99%).
Study Summary
• The benefit was driven by reduced ischemic stroke in the qualifying artery territory (0.4% vs 7.5%) and reduced need for revascularization (1.2% vs 8.3%) beyond 30 days, outweighing numerically higher periprocedural risk (stroke/death within 30 days: 3.2% vs 1.6%).
• Arterial dissection occurred in 14.5% of balloon angioplasty patients; the first positive RCT of endovascular treatment over medical management for sICAS.
Intervention
Submaximal balloon angioplasty (50–70% of proximal artery diameter) with dedicated intracranial balloon (Sinomed) + aggressive medical management vs. aggressive medical management alone (DAPT 90 days + risk factor control)
Inclusion Criteria
Age 35–80 years, recent TIA (<90 days) or ischemic stroke (14–90 days) attributed to 70–99% atherosclerotic stenosis of a major intracranial artery (ICA C4–C7, M1, V4, or basilar), while receiving at least 1 antithrombotic or risk factor treatment, normal distal artery, mRS <3
Study Design
Arms: Balloon angioplasty + aggressive medical management vs. aggressive medical management alone
Patients per Arm: 501 total (Balloon angioplasty: 249, Medical management: 252)
Outcome
• 30-day stroke/death: 3.2% vs 1.6% (HR 2.05, P=0.24); beyond 30 days qualifying artery ischemic stroke: 0.4% vs 7.5%; qualifying artery revascularization: 1.2% vs 8.3%.
• Procedural complications: arterial dissection 14.5%, sICH 1.2% vs 0.4%; 1-year mRS shift favored angioplasty (generalized OR 1.26, P=0.01).
Bottom Line
Balloon angioplasty plus aggressive medical management significantly reduced the 1-year composite primary outcome (4.4% vs 13.5%; HR 0.32) driven by lower rates of qualifying artery ischemic stroke and revascularization beyond 30 days, despite numerically higher periprocedural risk. This is the first positive RCT of endovascular treatment over medical management for sICAS, though procedural complications including 14.5% arterial dissection remain a concern.
Major Points
- Primary composite outcome significantly lower with balloon angioplasty: 4.4% vs 13.5% (HR 0.32, 95% CI 0.16–0.63; P<0.001).
- 30-day stroke or death was numerically higher with angioplasty (3.2% vs 1.6%; HR 2.05, P=0.24) — Kaplan-Meier curves crossed at 30 days.
- Beyond 30 days through 1 year: qualifying artery ischemic stroke 0.4% vs 7.5%; qualifying artery revascularization 1.2% vs 8.3%.
- Post hoc analysis removing revascularization from composite still favored angioplasty (3.6% vs 9.1%; HR 0.39, P=0.01).
- Arterial dissection occurred in 14.5% of angioplasty patients; 71.4% of these underwent rescue stenting.
- sICH rate 1.2% (angioplasty) vs 0.4% (medical management).
- 1-year mRS shift favored angioplasty (generalized OR 1.26, 95% CI 1.06–1.45; P=0.01).
- Disabling stroke (mRS ≥2 at 1 year) was lower with angioplasty (2.4% vs 7.1%; P=0.02).
- Restenosis rate of the qualifying artery within 1 year was 15.7% in the angioplasty group; only 2.0% had TIA/stroke related to restenosis.
- All prespecified subgroup point estimates favored balloon angioplasty, with no significant interactions.
- First positive RCT of any endovascular approach over medical management for sICAS, after negative results from SAMMPRIS, VISSIT, and CASSISS (all stenting trials).
- Submaximal inflation (50–70% of proximal diameter) may reduce snowplowing effect on perforator branches compared to stenting.
- Median time from qualifying event to randomization was 34 days (angioplasty) and 32 days (medical), longer than SAMMPRIS (7 days) but shorter than CASSISS (38 days).
- 84.4% of qualifying events were ischemic stroke; 40.0% had border zone infarction, a marker of hemodynamic compromise.
Study Design
- Study Type
- Investigator-initiated, multicenter, randomized, open-label, blinded endpoint trial (PROBE design)
- Randomization
- Yes
- Blinding
- Open-label with blinded endpoint evaluation. Clinical event adjudication committee blinded to group assignment. Neuroimaging core lab of independent neuroradiologists masked to all clinical information.
- Sample Size
- 501
- Follow-up
- 12 months (primary; up to 3 years planned)
- Centers
- 31
- Countries
- China
Primary Outcome
Definition: Composite of any stroke or death within 30 days after enrollment or after balloon angioplasty, or any ischemic stroke in the qualifying artery territory or revascularization of the qualifying artery after 30 days through 12 months
| Control | Intervention | HR/OR | P-value |
|---|---|---|---|
| 34/252 (13.5%) | 11/249 (4.4%) | 0.32 (0.16–0.63) | P<0.001 |
Limitations & Criticisms
- Over half of enrolled patients (51.5%) were from the lead center, limiting generalizability — though post hoc center-effect adjustment showed similar results.
- All-Chinese population (98.6% Han Chinese); findings may not generalize to other ethnic populations.
- Composite primary outcome included revascularization, which is a soft endpoint partly driven by clinical decision-making — though post hoc analysis excluding revascularization still favored angioplasty.
- Kaplan-Meier curves crossed at 30 days, indicating higher early periprocedural risk with angioplasty before later benefit.
- Arterial dissection rate of 14.5% is high, with 71.4% of dissections requiring rescue stenting — partially undermining the 'angioplasty without stenting' concept.
- Sample size was revised downward from 802 to 512 during the trial due to COVID-19 pandemic and funding constraints.
- Interim analysis was forgone during sample size re-estimation; though blinded endpoint data were not accessed, this introduces methodological concern.
- Open-label design with potential for performance bias, although endpoint adjudication was blinded.
- Low baseline NIHSS (median 0) and high mRS 0–1 at admission (>91%) indicate a relatively well-recovered population, which may not represent the full spectrum of sICAS patients.
- Aggressive medical management group event rate (13.5%) was comparable to prior trials but may have been inflated by inclusion of revascularization as an endpoint.
- Long-term restenosis data and durability of balloon angioplasty effect beyond 1 year not yet available.
- Drug-coated balloons and drug-eluting stents were not assessed.
- Funded in part by Sino Medical Sciences Technology (manufacturer of the intracranial balloon catheter used in the trial).
Citation
JAMA. 2024;332(13):1059-1069. doi:10.1001/jama.2024.12829