Stenting versus medical treatment in patients with symptomatic vertebral artery stenosis: a randomised open-label phase 2 trial

doi:10.1016/S1474-4422(15)00017-4

The Lancet Neurology

Volume 14, Issue 6, June 2015, Pages 606-614

https://doi.org/10.1016/S1474-4422(15)00017-4 Get rights and content

Summary

Background

Patients with a recent vertebrobasilar transient ischaemic attack or ischaemic stroke and vertebral artery stenosis of at least 50% have a high risk of future vertebrobasilar stroke. Stenting of vertebral artery stenosis is promising, but of uncertain benefit. We investigated the safety and feasibility of stenting of symptomatic vertebral artery stenosis of at least 50%, and assessed the rate of vascular events in the vertebrobasilar supply territory to inform the design of a phase 3 trial.

Methods

Between Jan 22, 2008, and April 8, 2013, patients with a recent transient ischaemic attack or minor stroke associated with an intracranial or extracranial vertebral artery stenosis of at least 50% were enrolled from seven hospitals in the Netherlands in a phase 2 open-label trial with masked assessment of outcome. Patients were randomly allocated in a 1:1 ratio to stenting plus best medical treatment or best medical treatment alone by the local investigators using a web-based randomisation system. The primary outcome was the composite of vascular death, myocardial infarction, or any stroke within 30 days after the start of treatment. The secondary outcomes were stroke in the supply territory of the symptomatic vertebral artery during follow-up, the composite outcome during follow-up, and the degree of stenosis in the symptomatic vertebral artery at 12 months. The trial is registered, number ISRCTN29597900.

Findings

The trial was stopped after inclusion of 115 patients because of new regulatory requirements, including the use of a few prespecified stent types and external monitoring, for which no funding was available. 57 patients were assigned to stenting and 58 to medical treatment alone. Three patients in the stenting group had vascular death, myocardial infarction, or any stroke within 30 days after the start of treatment (5%, 95% CI 0–11) versus one patient in the medical treatment group (2%, 0–5). During a median follow-up of 3 years (IQR 1·3–4·1), seven (12%, 95% CI 6–24) patients in the stenting group and four (7%, 2–17) in the medical treatment group had a stroke in the territory of the symptomatic vertebral artery; 11 (19%) patients in the stenting group and ten (17%) in the medical treatment group had vascular death, myocardial infarction, or any stroke. The small size of the vertebral artery and stent artifacts did not allow exact grading of restenosis on CT angiography. During the complete period of follow-up, there were 60 serious adverse events (eight strokes) in the stenting group and 56 (seven strokes) in the medical treatment alone group.

Interpretation

Stenting of symptomatic vertebral artery stenosis is associated with a major periprocedural vascular complication in about one in 20 patients. In the population we studied, the risk of recurrent vertebrobasilar stroke under best medical treatment alone was low, questioning the need for and feasibility of a phase 3 trial.

Funding

Dutch Heart Foundation.

Introduction

About a quarter of patients with vertebrobasilar transient ischaemic attack or ischaemic stroke have atherosclerotic stenosis of at least 50% of the vertebral artery or basilar artery.1, 2 The presence of a symptomatic vertebral or basilar artery stenosis is associated with an increased risk of recurrent vertebrobasilar stroke, particularly in the first few weeks.1, 3, 4, 5 Endovascular treatment of symptomatic vertebral artery stenosis with percutaneous transluminal angioplasty (PTA) and stenting has been introduced as a promising option and is widely used in clinical practice.6, 7, 8 However, the safety and efficacy of stenting of symptomatic vertebral artery stenosis are uncertain.⁹

We assessed the safety and feasibility of stenting plus best medical treatment compared with best medical treatment alone in patients with symptomatic vertebral artery stenosis of at least 50% in the randomised phase 2 Vertebral Artery Stenting Trial (VAST). We also assessed the rates of vertebrobasilar stroke to inform effect estimates for a phase 3 trial.

Section snippets

Study design and patients

VAST was an open-label, randomised clinical trial¹⁰ in which patients were enrolled from seven hospitals in the Netherlands from Jan 22, 2008, to April 8, 2013. The protocol for VAST has been published previously.¹⁰ All seven participating centres had a team of investigators consisting of at least one stroke neurologist and an interventional neuroradiologist.

After the death of one patient from a complication of stenting, the trial executive committee put enrolment into the trial on hold on

Results

Of the 115 patients recruited, 57 were assigned to receive stents plus best medical treatment and 58 to receive best medical treatment alone (figure 1). 50 (88%) patients allocated to the stenting group had a stent placed (n=49) or had PTA without stenting (n=1). In the stent group, one patient refused the allocated treatment, one patient had a cerebellar haemorrhage before stenting could be done, one patient had occlusion of the vertebral artery before stenting could be done, and four patients

Discussion

In the current study, the periprocedural risk of major vascular events associated with stenting of symptomatic vertebral artery stenosis of at least 50% was 5%. The cumulative incidence of recurrent vertebrobasilar stroke in patients on best medical treatment was 7% during a median follow-up of 3 years, questioning the feasibility of and the need for a phase 3 trial to assess the benefit of stenting in a comparable patient population.

The presence of symptomatic vertebrobasilar stenosis of at

References (24)

HS Markus et al.
Posterior circulation ischaemic stroke and transient ischaemic attack: diagnosis, investigation, and secondary prevention
Lancet Neurol
(2013)
O Eberhardt et al.
Stenting of vertebrobasilar arteries in symptomatic atherosclerotic disease and acute occlusion: case series and review of the literature
J Vasc Surg
(2006)
GA Antoniou et al.
Percutaneous transluminal angioplasty and stenting in patients with proximal vertebral artery stenosis
J Vasc Surg
(2012)
PM Rothwell et al.
Analysis of pooled data from the randomised controlled trials of endarterectomy for symptomatic carotid stenosis
Lancet
(2003)
J Hofmeijer et al.
New algorithm for treatment allocation reduced selection bias and loss of power in small trials
J Clin Epidemiol
(2008)
CP Derdeyn et al.
Aggressive medical treatment with or without stenting in high-risk patients with intracranial artery stenosis (SAMMPRIS): the final results of a randomised trial
Lancet
(2014)
PM Rothwell et al.
Effect of urgent treatment of transient ischaemic attack and minor stroke on early recurrent stroke (EXPRESS study): a prospective population-based sequential comparison
Lancet
(2007)
L Marquardt et al.
Incidence and prognosis of > or = 50% symptomatic vertebral or basilar artery stenosis: prospective population-based study
Brain
(2009)
E Flossmann et al.
Prognosis of vertebrobasilar transient ischaemic attack and minor stroke
Brain
(2003)
G Gulli et al.
Vertebrobasilar stenosis predicts high early recurrent stroke risk in posterior circulation stroke and TIA
Stroke
(2009)

G Gulli et al.

Stroke risk after posterior circulation stroke/transient ischemic attack and its relationship to site of vertebrobasilar stenosis: pooled data analysis from prospective studies

Stroke

(2013)

AN Stayman et al.

A systematic review of stenting and angioplasty of symptomatic extracranial vertebral artery stenosis

Stroke

(2011)

Cited by (138)

Intrinsic stenosing and occlusive pathologies of the vertebral artery: A narrative review
2024, Neurochirurgie
Intrinsic pathologies of the vertebral arteries, such as atherosclerosis, dissection, fibromuscular dysplasia, radionecrosis and vasculitis, are important causes of vertebrobasilar insufficiency and cerebrovascular events. This review focuses on non-aneurysmal intrinsic stenosing and occlusive pathologies, covering their epidemiology, diagnosis, and treatment options. It also provides a detailed summary of key clinical presentations and syndromes, including an in-depth examination of lateral medullary syndrome, historically known as Wallenberg's syndrome, which is arguably the most emblematic condition resulting from vertebral artery involvement and is depicted in an illustrative cartoon.
The morphology of occlusion stump for endovascular recanalization in non-acute vertebral ostial occlusion
2024, Journal of Clinical Neuroscience
Non-acute vertebral ostial occlusion (VOO) is a debilitating condition with significant mortality and morbidity rates. However, currently, there is no consensus on the optimal treatment strategy for VOO. This study aims to examine the feasibility, effectiveness, and safety of endovascular recanalization in patients with VOO.
We conducted a retrospective review of data from 21 consecutive patients with VOO who underwent endovascular recanalization between May 2018 and August 2023. The patients were divided into two groups based on a new angiographic classification proposed by Gao et al. Type I (tapered stump group) included patients with non-acute extracranial vertebral artery ostial occlusion presenting a tapered occlusion stump. Type II (nontapered stump group) consisted of patients with a nontapered occlusion stump. We collected data on recanalization rates, perioperative complications, and follow-up outcomes.
Our analysis included data from a total of 21 patients (22 lesions) with a mean age of 64.6 ± 10.6 years. The technical success rate was 66.7 % (14/21), and the rate of periprocedural complications was 14.3 % (3/21). The success rate of transitioning from the tapered stump group to the nontapered stump group was 90.9 % (10/11) and 40 % (4/10), respectively (P = 0.024). The perioperative complication rate for type I and type II patients was 18.2 % (2/11) and 10 % (1/10), respectively. Among these patients, 18 cases underwent endovascular recanalization using transfemoral access, while 3 patients underwent transradial access after failed transfemoral access, with successful outcomes for two patients.
This study suggests that endovascular recanalization may offer a safe, effective, and feasible treatment option for VOO patients. Additionally, the proposed angiographic classification may serve as a useful guide in selecting suitable candidates for surgery.
Percutaneous transluminal angioplasty and stenting of post-irradiation stenosis of the vertebral artery
2023, Journal of Neuroradiology
The outcomes of percutaneous transluminal angioplasty and stenting (PTAS) in patients with medically refractory post-irradiation stenosis of the vertebral artery (PISVA) have not been clarified.
This retrospective study evaluated the safety and outcomes of PTAS in patients with severe PISVA compared with their radiation-naïve counterparts (non-RT group).
Patients with medically refractory severe symptomatic vertebral artery stenosis and undergoing PTAS between 2000 and 2021 were classified as the PISVA group or the non-RT group. The periprocedural neurological complications, periprocedural brain magnetic resonance imaging, the extent of symptom relief, and long-term stent patency were compared.
As compared with the non-RT group (22 cases, 24 lesions), the PISVA group (10 cases, 10 lesions) was younger (62.0 ± 8.6 vs 72.4 ± 9.7 years, P = 0.006) and less frequently had hypertension (40.0% vs 86.4%, P = 0.013) and diabetes mellitus (10.0% vs 54.6%, P = 0.024). Periprocedural embolic infarction was not significantly different between the non-RT group and the PISVA group (37.5% vs 35.7%, P = 1.000). At a mean follow-up of 72.1 ± 58.7 (3–244) months, there was no significant between-group differences in the symptom recurrence rate (0.00% vs 4.55%, P = 1.000) and in-stent restenosis rate (10.0% vs 12.5%, P = 1.000).
PTAS of severe medically refractory PISVA is effective in the management of vertebrobasilar ischemic symptoms in head and neck cancer patients. Technical safety and outcome of the procedure were like those features in radiation-naïve patients.
Editor's Choice – European Society for Vascular Surgery (ESVS) 2023 Clinical Practice Guidelines on the Management of Atherosclerotic Carotid and Vertebral Artery Disease
2023, European Journal of Vascular and Endovascular Surgery
Citation Excerpt :
In a review of 600 patients with symptomatic VA stenoses treated by angioplasty/stenting, intracranial stenting incurred higher procedural stroke risks (10.6%) versus extracranial VA stenoses (1.3%).612 Table 41 details an individual patient meta-analysis of data from 354 symptomatic patients with 50–99% VA stenoses who were randomised within VIST, VAST, and SAMMPRIS.29,613,614 There were no data from VISSIT (did not collaborate) or CAVATAS (VA angioplasty only).77
A Comparison of Different Endovascular Treatment for Vertebral Artery Origin Stenosis
2022, World Neurosurgery
To compare the safety and efficacy of stenting with drug-eluting stent (DES), stenting with bare mental stent (BMS), and angioplasty alone with drug-coated balloon (DCB) in patients with symptomatic vertebral artery origin stenosis (VAOS) who did not respond to aggressive medical management.
We performed a retrospective analysis of consecutive patients with symptomatic VAOS who underwent endovascular treatment between December 2018 and November 2021 at our institution. The main outcome compared were technical success, perioperative complications, residual stenosis, stroke recurrence, progression of residual stenosis, and restenosis.
A total of 46 patients were included: 29 were stented with DES, 12 were stented with BMS, and 5 received angioplasty alone with DCB. Technical success was achieved in 100%, 100%, and 60%, respectively (P = 0.008). Residual stenosis was 10.8%, 20.2%, and 51.2%, respectively (P < 0.001). Perioperative complications occurred only in 1 case in the DES group (P = 1.00). During a mean follow-up of 14.1 months, stroke recurrence rate was 6.9%, 16.7%, and 0% respectively (P = 0.73). Absolute progression of residual stenosis was 10.1%, 34.9%, and –8.0%, respectively (P < 0.001). Restenosis rate was 6.9%, 50.0%, and 20.0%, respectively (P = 0.007).
In patients with symptomatic VAOS who did not respond to aggressive medical management, stenting with DES shows superiority in the lowering the restenosis rate compared with stenting with BMS. Angioplasty alone with DCB is associated with the slowest progression of stenosis in spite of moderate residual stenosis.
Posterior Circulation Ischaemic Stroke
2022, American Journal of the Medical Sciences
Posterior circulation ischaemic stroke (PCIS) is a disease of high mortality and morbidity. They account for 20–25% of all ischaemic strokes. However, it is relatively under-researched and requires more clinical attention, since it carries worse functional outcomes. Vertigo, visual disturbances and sensory/motor disturbances are commonly observed in patients with PCIS. Large artery atherosclerosis and embolism are the main causes of PCIS, while there is growing evidence that vertebrobasilar dolichoectasia is a key associative factor. Hypertension is the most common risk factor, while diabetes mellitus is more specific to PCIS. PCIS is diagnosed through a range of neuroimaging techniques, which respectively examine structural brain abnormalities, vascular patency and perfusion. PCIS, in line with ischaemic stroke in general, necessitates medical treatment and lifestyle modifications. This includes smoking cessation, weight control, and alterations in dietary habits. Aspirin use also significantly improves survival outcomes. While intravascular and intra-arterial thrombolysis improve clinical outcomes, this is not proven conclusively for stenting and angioplasty. Future research on PCIS can focus on multi-centre epidemiological studies, clinically significant anatomical variants, and collateralisation.

View all citing articles on Scopus

^†: Members listed at end of paper

View full text

ArticlesStenting versus medical treatment in patients with symptomatic vertebral artery stenosis: a randomised open-label phase 2 trial

Summary

Background

Methods

Findings

Interpretation

Funding

Introduction

Section snippets

Study design and patients

Results

Discussion

Lancet Neurol

J Vasc Surg

J Vasc Surg

Lancet

J Clin Epidemiol

Lancet

Lancet

Incidence and prognosis of > or = 50% symptomatic vertebral or basilar artery stenosis: prospective population-based study

Brain

Prognosis of vertebrobasilar transient ischaemic attack and minor stroke

Brain

Vertebrobasilar stenosis predicts high early recurrent stroke risk in posterior circulation stroke and TIA

Stroke

Stroke risk after posterior circulation stroke/transient ischemic attack and its relationship to site of vertebrobasilar stenosis: pooled data analysis from prospective studies

Stroke

A systematic review of stenting and angioplasty of symptomatic extracranial vertebral artery stenosis

Stroke

Articles
Stenting versus medical treatment in patients with symptomatic vertebral artery stenosis: a randomised open-label phase 2 trial