VIST
Vertebral artery stenting to prevent recurrent stroke in symptomatic vertebral artery stenosis: the VIST RCT
Year of Publication: 2019
Authors: Hugh S Markus, Susanna C Larsson, John Dennis, ..., Andrew Clifton and Peter M Rothwell
Journal: Health Technology Assessment
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).
Link: https://www.journalslibrary.nihr.ac.uk/hta/hta23410/#/
PDF: Clinical Question
To compare the risks and benefits of vertebral angioplasty and stenting with best medical treatment (BMT) alone for recently symptomatic vertebral artery (VA) stenosis in preventing recurrent stroke.
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).
Design
Study Type: Prospective, randomised, open-label, parallel-group, blinded end-point clinical trial (Phase III)
Randomization: 1
Blinding: Independent adjudication committee masked to treatment allocation for all primary and secondary endpoints.
Enrollment Period: October 23, 2008, to February 4, 2015 (recruitment ended prematurely)
Follow-up Duration: At least 1 year for every patient; median 3.5 years.
Centers: 14
Countries: UK
Sample Size: 182
Analysis: Intention-to-treat basis; Cox proportional hazards regression models for HRs with 95% CIs. Kaplan-Meier survival analysis with log-rank test. Two-sided statistical tests, p-value <0.05 significant. Post hoc analyses adjusting for time from last symptoms to randomization. Stata version 14.1.
Inclusion Criteria
- Women or men aged > 20 years.
- Symptomatic vertebral stenosis resulting from presumed atheromatous disease.
- Severity of stenosis at least 50% as determined by MRA, CTA, or intra-arterial angiography.
- Symptoms of TIA or stroke within the previous 3 months (initially 6 months for pilot phase).
- Patients able to provide written informed consent, willing to be randomized to either treatment, and willing to participate in follow-up.
Exclusion Criteria
- Patients unwilling or unable to give informed consent.
- Patients unwilling to accept randomization to either treatment group.
- Vertebral stenosis caused by acute dissection.
- Patients in whom vertebral stenting was felt to be technically not feasible (e.g., access problems).
- Previous stenting in the randomized artery.
- Women who were pregnant or lactating.
Baseline Characteristics
| Characteristic | Control | Active |
|---|---|---|
| Age (years), mean (SD) [range] | 66.6 (10.2) [45-86] | 68.3 (9.2) (44-89] |
| Male, n (%) | 75 (85) | 73 (80) |
| Treated hypertension, n (%) | 60 (68) | 66 (73) |
| Systolic blood pressure (mmHg), mean (SD) | 139.3 (2.3) | 138.4 (2.0) |
| Diastolic blood pressure (mmHg), mean (SD) | 79.5 (1.3) | 77.0 (1.3) |
| Treated hyperlipidaemia, n (%) | 77 (88) | 77 (85) |
| Total cholesterol (mmol/l), mean (SD) | 4.5 (0.14.) | 4.4 (0.13) |
| Treated diabetes mellitus, n (%) | 19 (22) | 20 (22) |
| Current smoker, n (%) | 25 (29) | 18 (20) |
| Ischaemic heart disease, n (%) | 9 (10) | 19 (21) |
| Peripheral artery disease, n (%) | 4 (4.6) | 9 (9.9) |
| Atrial fibrillation, n (%) | 8 (9.1) | 10 (11) |
| Qualifying event - Ischaemic stroke | 58 (66) | 63 (69) |
| Qualifying event - TIA | 30 (34) | 28 (31) |
| Days between last vertebrobasilar event and randomisation, median | 24.5 | 14.0 |
| ≤14 days since last vertebrobasilar event | 30 (34) | 47 (52) |
| Location of VA target stenosis - Extracranial (V1-V3), n (%) | 74 (84) | 74 (81) |
| Location of VA target stenosis - V1, n | 70 | 71 |
| Location of VA target stenosis - V2 or V3, n | 4 | 3 |
| Location of VA target stenosis - Intracranial (V4), n (%) | 14 (16) | 17 (19) |
| Modified Rankin Scale score, median (IQR) | 1 (1-2) | 2 (1-2) |
| Days from randomisation to stenting, mean (SD) | 16.1 (1.9) |
Arms
| Field | Vertebral angioplasty and stenting plus BMT | Control |
|---|---|---|
| Intervention | Vertebral angioplasty and stenting plus best medical treatment (BMT). Stenting was preferred for proximal stenosis, while distal stenosis choice was at radiologist's discretion. Recommended antiplatelet therapy during procedure: clopidogrel and aspirin (loading dose of clopidogrel at least 12h before). Continued for at least 1 month post procedure, then standard antiplatelet therapy for stroke prevention. BMT included antiplatelet therapy/anticoagulation and control of medical risk factors. | Best medical treatment (BMT) alone. BMT included antiplatelet therapy or anticoagulation (when appropriate) and control of medical risk factors (hypertension, smoking, hyperlipidaemia). Specific drugs not mandated. |
| Duration | Median 3.5 years | Median 3.5 years |
Outcomes
| Outcome | Type | Control | Intervention | HR / OR / RR | P-value |
|---|---|---|---|---|---|
| Occurrence of fatal or non-fatal stroke in any arterial territory (including periprocedural stroke) during follow-up. | Primary | 12 patients (including two fatal strokes) | 5 patients (including one fatal stroke) | 0.4 | 0.08 |
| Fatal or non-fatal stroke in any arterial territory or TIA (exploratory) | Secondary | 0.5 | 0.05 | ||
| Fatal or non-fatal stroke in any arterial territory within 90 days | Secondary | 0.71 | 0.66 | ||
| Death from any cause during follow-up | Secondary | 0.86 | 0.76 | ||
| Periprocedural stroke or death (within 30 days of procedure) | Secondary | 3/7.2 events/person-year | 3/7.0 events/person-year | 0.98 | 0.98 |
| Posterior circulation stroke | Secondary | 8/291 events/person-year | 4/308 events/person-year | 0.47 | 0.39 |
| Posterior circulation stroke or TIA | Secondary | 19/255 events/person-year | 11/291 events/person-year | 0.53 | 0.09 |
| Restenosis in treated artery | Secondary | N/A (no stent placed in medical group) | 3 stent occlusions among 47 stented patients with follow-up CTA/MRA (2 in V1, 1 in V2); degree of stenosis could not be measured because stent obscured lumen | Not reported | |
| Any adverse events | Adverse | 29 (33.0%) | 34 (37.4%) | ||
| Cardiovascular events, any | Adverse | 6 (6.9%) | 7 (7.7%) | ||
| Angina | Adverse | 1 (1.1%) | 2 (2.2%) | ||
| Atrial fibrillation | Adverse | 2 (2.3%) | 1 (1.1%) | ||
| Brachial artery dissecting aneurysm | Adverse | 0 (0%) | 1 (1.1%) | ||
| Cardiac failure | Adverse | 1 (1.1%) | 2 (2.2%) | ||
| Coronary artery bypass graft | Adverse | 1 (1.1%) | 0 (0%) | ||
| Myocardial infarction | Adverse | 0 (0%) | 1 (1.1%) | ||
| Ventricular tachycardia | Adverse | 1 (1.1%) | 0 (0%) | ||
| Other events, any | Adverse | 23 (26.1%) | 27 (29.7%) | ||
| Subarachnoid haemorrhage (during stenting, fatal) | Adverse | 0 | 1 | ||
| Periprocedural brainstem stroke (non-fatal) | Adverse | 0 | 1 | ||
| Non-fatal stroke within 30 days of extracranial stenting | Adverse | 0 | 1 |
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.
Subgroup Analysis
Exploratory post hoc analyses were performed adjusting for time from last symptoms to randomisation, and also limited to patients randomised within 2 weeks after the last symptom. Subgroup analysis of extracranial vs. intracranial VA stenosis was also performed. The study was not powered for subgroup conclusions.
Funding
National Institute for Health Research (NIHR) Health Technology Assessment programme. Pilot phase funded by the Stroke Association.
Based on: VIST (Health Technology Assessment, 2019)
Authors: Hugh S Markus, Susanna C Larsson, John Dennis, ..., Andrew Clifton and Peter M Rothwell
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).
Content summarized and formatted by NeuroTrials.ai.