PDF: VIST
(2019)Objective
To evaluate whether vertebral artery stenting plus best medical therapy (BMT) is superior to BMT alone in preventing recurrent stroke in patients with recently symptomatic vertebral artery stenosis.
Study Summary
Intervention
Prospective, randomized, open-label, blinded-endpoint trial conducted at 14 hospitals in the UK. Patients (N=182) with symptomatic vertebral artery stenosis ≥50% were randomized 1:1 to vertebral stenting plus BMT (n=91) or BMT alone (n=88). Median follow-up: 3.5 years. Primary outcome: any stroke (fatal or non-fatal) in any arterial territory.
Study Design
Arms: Array
Outcome
• Post hoc adjusted HR: 0.34 (p=0.046); HR 0.30 for those randomized ≤2 weeks of symptoms (p=0.048)
• Intracranial stenting had higher perioperative risk (2 strokes including 1 fatal)
• No significant differences in secondary outcomes (posterior circulation stroke, death, restenosis)
• Stenting was safe in extracranial VA stenosis, but trial was underpowered
Bottom Line
The VIST trial, the largest randomized controlled trial to date on stenting for symptomatic VA stenosis, found no significant difference in the risk of recurrent stroke between the stent and best medical treatment groups. While stenting for extracranial stenosis appeared safe with low periprocedural risk, the study was underpowered due to early termination, and further larger trials are needed to confirm any potential benefit.
Major Points
- VIST was a prospective, randomized, open, parallel, blinded end-point clinical trial conducted in 14 UK hospitals.
- 182 patients were initially enrolled (91 assigned to stenting/angioplasty plus BMT, 88 to BMT alone), but recruitment was stopped early due to slower than anticipated recruitment and cessation of funding, falling short of the planned 540 patients.
- The median follow-up was 3.5 years. Of stented patients, 78.7% had extracranial stenosis and 21.3% had intracranial stenosis.
- The primary end point (fatal or non-fatal stroke in any arterial territory) occurred in 5 patients in the stent group and 12 in the medical group (Hazard Ratio [HR] 0.40, 95% CI 0.14 to 1.13; p=0.08).
- No perioperative complications occurred with extracranial stenting; two strokes occurred during intracranial stenting (one fatal subarachnoid hemorrhage, one non-fatal brainstem stroke).
- Post hoc analysis, adjusting for time from last symptoms to randomization (shorter in the stent group), showed a significant benefit for stenting (HR 0.34, 95% CI 0.12 to 0.98; p=0.046). A further post hoc analysis limited to patients randomized within 2 weeks after last symptom also showed a significant benefit (HR 0.30, 95% CI 0.09 to 0.99; p=0.048). These post-hoc findings should be treated with caution.
- Meta-analysis with other trials showed no overall benefit of stenting for any type of vertebral stenosis (Relative Risk [RR] 0.89, 95% CI 0.36 to 2.21).
Study Design
- Study Type
- Prospective, randomised, open-label, parallel-group, blinded end-point clinical trial (Phase III)
- Randomization
- Yes
- Blinding
- Independent adjudication committee masked to treatment allocation for all primary and secondary endpoints.
- Sample Size
- 182
- Follow-up
- At least 1 year for every patient; median 3.5 years.
- Centers
- 14
- Countries
- UK
Primary Outcome
Definition: Occurrence of fatal or non-fatal stroke in any arterial territory (including periprocedural stroke) during follow-up.
| Control | Intervention | HR/OR | P-value |
|---|---|---|---|
| 12 patients (including two fatal strokes) | 5 patients (including one fatal stroke) | 0.4 (0.14 to 1.13) | 0.08 |
Limitations & Criticisms
- The study was underpowered due to failure to reach target recruitment (182 patients recruited vs 540 planned) because funding was halted due to slower than anticipated recruitment. This limits the ability to draw definitive conclusions.
- There was a high rate of non-confirmation of stenosis (<50% on DSA) in the stented group (23 out of 91 randomized), emphasizing the need for stricter quality control of non-invasive imaging in future studies.
- Despite randomization, there was an imbalance in time from last symptoms to randomization, with the stent group having a shorter interval. This is a potential confounder, although post hoc analyses attempted to adjust for it.
- The primary endpoint (fatal or non-fatal stroke) showed only a non-statistically significant reduction, and the post-hoc analyses showing significant benefit should be interpreted with caution.
- It proved difficult to unequivocally determine whether some strokes were posterior circulation, leading to exclusion of a secondary endpoint (disabling stroke).
- Repeat imaging at 1 year to check for vessel patency was encouraged but not mandated, potentially leading to incomplete data on restenosis.
- Cost-effectiveness data were not available due to early termination and funding withdrawal for this analysis.
Citation
Markus HS, Larsson SC, Dennis J, Kuker W, Schulz UG, Ford I, et al. Vertebral artery stenting to prevent recurrent stroke in symptomatic vertebral artery stenosis: the VIST RCT. Health Technol Assess 2019;23(41).