Hugh S Markus1, Patrik Michel2. 1. Department of Clinical Neurosciences, University of Cambridge, Cambridge, UK. 2. Stroke Center, Neurology Service, Department of Clinical Neurosciences, Lausanne University Hospital and University of Lausanne, Lausanne, Switzerland.
Abstract
One-fifth of strokes occur in the territory of the posterior circulation, but their management, particularly acute reperfusion therapy and neurointervention procedures for secondary prevention, has received much less attention than similar interventions for the anterior circulation. In this review, we overview the treatment of posterior circulation stroke, including both interventions in the acute setting and secondary prevention. We focus on areas in which the management of posterior circulation stroke differs from that of stroke in general and highlight recent advances.Effectiveness of acute revascularization of posterior circulation strokes remains in large parts unproven. Thrombolysis seems to have similar benefits and lower hemorrhage risks than in the anterior circulation. The recent ATTENTION and BAOCHE trials have demonstrated that thrombectomy benefits strokes with basilar artery occlusion, but its effect on other posterior occlusion sites remains uncertain. Ischemic and hemorrhagic space-occupying cerebellar strokes can benefit from decompressive craniectomy.Secondary prevention of posterior circulation strokes includes aggressive treatment of cerebrovascular risk factors with both drugs and lifestyle interventions and short-term dual anti-platelet therapy. Randomized controlled trial (RCT) data suggest basilar artery stenosis is better treated with medical therapy than stenting, which has a high peri-procedural risk. Limited data from RCTs in stenting for vertebral stenosis suggest that intracranial stenosis is currently best treated with medical therapy alone; the situation for extracranial stenosis is less clear where stenting for symptomatic stenosis is an option, particularly for recurrent symptoms; larger RCTs are required in this area.
One-fifth of strokes occur in the territory of the posterior circulation, but their management, particularly acute reperfusion therapy and neurointervention procedures for secondary prevention, has received much less attention than similar interventions for the anterior circulation. In this review, we overview the treatment of posterior circulation stroke, including both interventions in the acute setting and secondary prevention. We focus on areas in which the management of posterior circulation stroke differs from that of stroke in general and highlight recent advances.Effectiveness of acute revascularization of posterior circulation strokes remains in large parts unproven. Thrombolysis seems to have similar benefits and lower hemorrhage risks than in the anterior circulation. The recent ATTENTION and BAOCHE trials have demonstrated that thrombectomy benefits strokes with basilar artery occlusion, but its effect on other posterior occlusion sites remains uncertain. Ischemic and hemorrhagic space-occupying cerebellar strokes can benefit from decompressive craniectomy.Secondary prevention of posterior circulation strokes includes aggressive treatment of cerebrovascular risk factors with both drugs and lifestyle interventions and short-term dual anti-platelet therapy. Randomized controlled trial (RCT) data suggest basilar artery stenosis is better treated with medical therapy than stenting, which has a high peri-procedural risk. Limited data from RCTs in stenting for vertebral stenosis suggest that intracranial stenosis is currently best treated with medical therapy alone; the situation for extracranial stenosis is less clear where stenting for symptomatic stenosis is an option, particularly for recurrent symptoms; larger RCTs are required in this area.
Stroke is globally the second leading cause of death and the third cause of death and disability.
One-fifth of strokes occur in the vertebrobasilar territory (also known as
posterior) circulation.
Diagnosis of posterior circulation stroke and transient ischemic attack (TIA)
can be more challenging than anterior circulation syndromes, and widely used
screening protocols such as the face-arm-speech test (FAST) are less sensitive.
Optimal management of posterior circulation stroke, particularly acute
reperfusion therapy and neurointervention procedures for secondary prevention, has
received much less attention than similar interventions for the anterior circulation.
However, recent research and ongoing studies are improving our understanding.
In this review, we cover the treatment of posterior circulation stroke, covering
both interventions in the acute setting and secondary prevention. We focus on areas
in which management of posterior circulation stroke differs from that of stroke in
general and highlight recent advances.
Methods
The authors conducted a literature search on PubMed from its inception to 29 March
2022. Only English-language articles were reviewed and included. All searches
included the terms “posterior circulation,” “brainstem,” “cerebellar,” “occipital,”
“thalamic,” “basilar,” “vertebral,” and “posterior cerebral.” We added the following
terms with an “AND” function: for acute revascularization: “thrombolysis,”
“alteplase,” “rtPA,” “endovascular treatment,” “thrombectomy,” “stentretriever,”
“thromboaspiration”; “haemorrhage” and “haemorrhagic transformation”; for
decompressive craniectomy: “mass effect,” “space occupying,” “edema”
“decompressive/decompression,” “craniectomy,” “drainage,” and “ventriculostomy”; for
posterior fossa hemorrhage: “haemorrhage”; and for secondary prevention:
“antiplatelet,” “intensive,” “angioplasty,” and “stenting.” Finally, the following
filters were applied during the search and again when manually selecting articles:
“case-control study,” “cohort study,” “comparative analysis,” “randomized trial,”
“meta-analysis,” “subgroup analysis,” and “pooled analysis.” In the retrieved
articles, the reference lists were checked for further studies.
Acute management
Intravenous thrombolysis
We found no RCTs comparing intravenous thrombolysis (IVT) with antithrombotic
treatment for the posterior circulation alone. The International Stroke Trial-3
was one of the only IVT RCT where the site of stroke was recorded; in the
pre-specified subgroup analysis, posterior circulation strokes had benefits
similar to anterior circulation strokes.Retrospective analyses, despite their significant limitations, have shown similar
results. Long-term outcomes after IVT seem to be at least as favorable in the
posterior as in the anterior circulation (relative risk (RR): 1.19; 95%
confidence interval (CI), 1.06–1.33 for mRS 0–2), and the risk of symptomatic
intracranial hemorrhage (ICH) is about half (RR: 0.49, 0.32–0.75).
Another meta-analysis suggested a more frequent favorable outcome (odds
ratio (OR): 1.36, 1.08–1.71) and confirmed lower rates of ICH (OR: 0.32, 0.21–0.49).A specific concern is the optimal treatment for basilar artery occlusion (BAO),
which can have a devastating clinical outcome. A case series of 116 BAO patients
showed that distal clot location was more likely to recanalize with IVT and that
recanalization was associated with survival and improved outcome.
In the BASICS (Basilar Artery International Cooperation Study) registry
including 121/592 (20.4%) patients receiving IVT, this treatment was not
superior to antithrombotic treatment (adjusted RR: 0.94, 0.60–1.45 for poor
outcome) in mild-to-moderate strokes;
there was a possibility of better outcome in severe strokes (adjusted RR:
0.88, 0.76–1.01 for poor outcome). In a retrospective analysis of 110 patients
with BAO undergoing IVT before thrombectomy, IV tenecteplase led to a higher
rate of radiological reperfusion than IV alteplase,
and an RCT comparing these two drugs before endovascular treatment (EVT)
is underway (Post-Eternal: https://clinicaltrials.gov/ct2/show/NCT04454788).In conclusion, thrombolysis for posterior circulation stroke appears to have
similar efficacy as for the anterior circulation, with lower hemorrhage risk. It
may be the treatment of choice in certain posterior circulation strokes,
including distal posterior cerebral artery (PCA) occlusion, and minor strokes.
IVT does not preclude subsequent endovascular therapy although the benefit of
bridging remains unproven in the posterior circulation.
Acute endovascular revascularization
EVT in the posterior circulation, in particular mechanical thrombectomy, is most
often performed and best studied for BAO. There are only a few observational
studies for PCA occlusions, and no systematic analyses of acute EVT in vertebral
artery (VA) occlusions.Adjusted retrospective comparisons of EVT in the posterior circulation as a whole
show similar clinical effectiveness to the anterior circulation in two large
studies[10,11] but worse outcome in another.
Rates of symptomatic ICH are similar to those in the anterior
circulation.
Endovascular treatment of BAO
Until very recently, there was no convincing data that endovascular treatment for
BAO was more effective than thrombolysis. In the non-randomized prospective
international BASICS registry,
288 (48.6%) of 592 patients underwent EVT. In mild-to-moderately severe
stroke, EVT was associated with worse 3-month outcome (mRS score of ⩽3) when
compared to IVT (adjusted RR: 1.49, 1.00–2.23 for poor outcome), and no
difference was seen in severe strokes (adjusted RR: 1.06, 0.91–1.22). Rates of
symptomatic ICH were higher with EVT than with thrombolysis. In contrast, the
non-randomized prospective Chinese BASILAR cohort showed a favorable 3-month
shift in mRS when compared to standard medical treatment (adjusted OR: 3.08, 2.09–4.55).
Symptomatic ICH was increased with EVT (7.1% vs 0.5%,
p < 0.001).The randomized controlled Chinese BEST trial (Basilar artery occlusion
Endovascular intervention versus Standard medical Treatment) was stopped after
131 patients due to a 22% crossover rate.
In the intention-to-treat analysis, it failed to show superiority of EVT
over standard medical treatment (with a 32% IVT rate): the adjusted OR for
favorable outcome (modified Rankin 0–3 at 3 months) was 1.74 (95% CI: 0.81–3.74)
(Figure 1).
Statistical significance likely has been lost because of the high cross-over
rate to EVT.
Figure 1.
Results of the four large randomized controlled trials of endovascular
treatment in patients with acute stroke from basilar artery
occlusion.[14,15] The odds or risk
ratios and 95% confidence intervals are shown for a favorable outcome
defined as modified Rankin score of 0–3 at 3 months.
BEST: Basilar artery occlusion Endovascular intervention versus Standard
medical Treatment;
BASICS: BASilar artery International Cooperation Study;
ATTENTION: EndovAscular TreaTmENT for acute basilar artery occlusION;
BAOCHE: Basilar Artery Occlusion CHinese Endovascular trial;
OR: odds ratio; RR: risk ratio.
Results of the four large randomized controlled trials of endovascular
treatment in patients with acute stroke from basilar artery
occlusion.[14,15] The odds or risk
ratios and 95% confidence intervals are shown for a favorable outcome
defined as modified Rankin score of 0–3 at 3 months.BEST: Basilar artery occlusion Endovascular intervention versus Standard
medical Treatment;
BASICS: BASilar artery International Cooperation Study;
ATTENTION: EndovAscular TreaTmENT for acute basilar artery occlusION;
BAOCHE: Basilar Artery Occlusion CHinese Endovascular trial;
OR: odds ratio; RR: risk ratio.The international BASICS RCT with 300 patients showed no benefit of EVT over best
medical treatment (with a 79% IVT rate), with a risk ratio for favorable
functional outcome at 3 months of 1.18 (95% CI: 0.92–1.50) (Figure 1).
In both BEST and BASICS, the symptomatic ICH rates were non-significantly
higher after EVT. Figure
2 shows a patient randomized in the BASICS trial with extensive
posterior fossa hypoperfusion, successfully recanalized with thrombectomy.
Figure 2.
87-year-old man with acute BAO, NIHSS = 8, randomized to endovascular
treatment in the BASICS trial:
(a) extensive hypoperfusion (blue color) on mean transit time on
perfusion CT from the medullary (A1) to midbrain (A2) levels.
Thrombolysis at 130 min. (b) Conventional angiography showing tight
stenosis at right vertebral origin (B1: arrow) and basilar artery
occlusion (B1, top of image); thrombectomy with basilar artery
recanalization at 4.2 h after onset, complicated by a non-stenosing
mid-basilar dissection (B2, arrow). (c) Sub-acute diffusion-weighted MRI
showing limited stroke volume in the right cerebellum (C1) and no
visible lesion in the midbrain (C2). Favorable outcome at 3 months with
minimal disability.
Copyright Patrik Michel.
87-year-old man with acute BAO, NIHSS = 8, randomized to endovascular
treatment in the BASICS trial:
(a) extensive hypoperfusion (blue color) on mean transit time on
perfusion CT from the medullary (A1) to midbrain (A2) levels.
Thrombolysis at 130 min. (b) Conventional angiography showing tight
stenosis at right vertebral origin (B1: arrow) and basilar artery
occlusion (B1, top of image); thrombectomy with basilar artery
recanalization at 4.2 h after onset, complicated by a non-stenosing
mid-basilar dissection (B2, arrow). (c) Sub-acute diffusion-weighted MRI
showing limited stroke volume in the right cerebellum (C1) and no
visible lesion in the midbrain (C2). Favorable outcome at 3 months with
minimal disability.Copyright Patrik Michel.However, two recent trials presented at the European Stroke Conference 2022,
after our systematic review was performed, showed convincing data on the
effectiveness of EVT for BAO.
ATTENTION (EndovAscular TreaTmENT for acute basilar artery occlusION)
recruited patients within 0–12 h from the estimated time of stroke onset in China.
A total of 340 patients were randomly assigned to thrombectomy or best
medical management in a 2:1 ratio. There was a highly significant improvement in
the primary endpoint of modified Rankin score 0–3 at 90 days which was achieved
in 104/226 (46%) of the endovascular therapy group and 26/114 (22.8%) of the
best medical management group; adjusted risk ratio of 2.1 (95% CI: 1.5–3.0).
About one-third of patients received IVT. There was a trend to more
symptomatic ICH with thrombectomy, but also to less mortality at 90 days.BAOCHE (Basilar Artery Occlusion CHinese Endovascular trial) differed in that it
recruited patients within 6 to 24 h of symptom onset where the patient was
ineligible for IV thrombolysis or had received IVT without recanalization.
The planned sample size was 318, but after a planned interim analysis
after 212 patients, the data and safety monitoring committee recommended early
termination of the trial due to highly significant differences between the two
treatments. In 217 patients available for the final analysis, 51 of 110 (46.4%)
randomized to thrombectomy achieved mRS 0–3 at 90 days, compared with 26/107
(24.3%) receiving best medical therapy, giving an adjusted OR of improved
outcome of 2.92 (95% CI: 1.56–5.47).
Despite an increase of symptomatic ICH and early mortality with ICH, this
was the first EVT trial to demonstrate a reduction of 90-day mortality.It is not yet known whether these two trials confirm the absence of thrombectomy
benefit in patients with NIHSS scores below 10, as seen in BASICS. Together,
these two new trials present convincing data that thrombectomy improves outcome
in BAO up to 24 h after symptom onset.Retrospective analyses suggest that better outcome in EVT-treated BAO is
associated with earlier treatment,
use of aspiration rather than stent retrievers,
local rather than general anesthesia,
and good collateral supply.
The first pass effect, defined as full recanalization in a single pass of
the endovascular thrombectomy device, is a predictor of good outcome for
posterior circulation EVT, as it is for the anterior circulation.
Endovascular treatment of PCA occlusions
For proximal PCA occlusion (P1 or P2 segments), retrospective analyses have shown
trends toward better outcomes with EVT versus best medical treatment (which may
include IVT).
A similar result was observed in the TOPMOST study evaluating distal PCA
occlusions (P2 and P3 segments).
None of these studies showed an increase in symptomatic ICH with EVT.In conclusion, EVT for posterior circulation stroke is feasible and has similar
complication rates to the anterior circulation. It is effective in BAO patients,
and the BAOCHE trial showed benefit in some patients up to 24 h. Further RCTs
are required to determine effectiveness and which subgroups benefit, in
particular in PCA and VA occlusion. IVT does not preclude subsequent
endovascular therapy although the benefit of bridging remains unproven in the
posterior circulation.
Imaging to improve patient selection for acute revascularization
Imaging the potential viability of ischemic tissue and collateral patterns could
help select patients most likely to respond, and be harmed, from such
treatments. The pc-ASPECTS (posterior circulation-Alberta Stroke Program Early
CT Score) estimates severe tissue hypoperfusion with non-viability and is
ideally assessed on CT-angiography source images.
It independently correlates with clinical outcomes and has also been
validated on magnetic resonance imaging diffusion-weighted imaging
(MRI-DWI).Focal hypoperfusion on CT in posterior circulation strokes is associated with
poorer outcome independently of other prognostic factors. Severe hypoperfusion
on CT within specific areas can be used to construct the Critical Area Perfusion
(CAP) score in BAO, correlating well with clinical outcome in EVT patients.
Similarly, the MRI-DWI-based PMT (pons-midbrain and thalamus) score
assesses the extent of DWI lesions in these regions in BAO; used in EVT
patients, it correlates well with functional outcome.As opposed to the anterior circulation, no scores exist describing occlusions
and/or collaterals encompassing the entire posterior circulation. For BAO, the
PC-CS (posterior circulation-collateral score) grading system quantifies
occlusions and collateral flow and emphasizes the importance of the posterior
communicating arteries. Clinical outcome correlated with the score independently
of treatment type.
The BATMAN (Basilar Artery on computed ToMography Angiography) score
considers both thrombus burden and collaterals with a lower score associated
with poorer outcome.
Such collateral scores are usually based on maximal intensity projections
of CTAs which are reconstructed routinely in acute stroke imaging; they are
calculated within 2–3 min.The importance of radiological selection for revascularization in BAO was also
shown by the ENDOSTROKE Study Group: in 148 BAO patients undergoing EVT,
successful recanalization did not predict outcome on its own, but MRI-based
selection was associated with a better outcome.
Similarly, the non-significant results of RCTs in BAO (see above) may
require more stringent radiological inclusion criteria for further trials, even
in early time windows.
Decompressive surgery for ischemic and hemorrhagic stroke with mass
effect
Cerebellar stroke, mainly in the inferior territory, may lead to secondary
swelling and space-occupying cerebellar infarction. In contrast to decompressive
hemicraniectomy for supratentorial stroke, RCTs for this condition are lacking.
Expert opinion suggests considering suboccipital decompression in selected
patients who deteriorate neurologically from impending brainstem
compression.[32,33] Removal of infarcted cerebellar tissue during this
procedure is controversial but may be considered in some situations. An example
is shown in Figure
3.
Figure 3.
46-year-old man with multilevel posterior circulation stroke and BAO.
NIHSS = 8. (a) Diffusion-weighted MRI showing extensive left inferior
(A1) and superior (A2) cerebellar infarcts. Basilar artery
recanalization by direct thrombectomy 8 h after last proof of good
health. (b) Plain CT 5 h later, showing early cerebellar mass effect.
(c) Plain CT after decompressive posterior craniectomy of 5 cm diameter,
still showing cerebellar mass effect. (d) Plain CT after second
craniectomy on day 3 with enlargement of craniectomy diameter to 7 cm
and partial resection (arrows) of left inferior(D1) and superior(D2)
cerebellar infarcts. Outcome at 3 months, independent, but not
working.
Copyright Patrik Michel.
46-year-old man with multilevel posterior circulation stroke and BAO.
NIHSS = 8. (a) Diffusion-weighted MRI showing extensive left inferior
(A1) and superior (A2) cerebellar infarcts. Basilar artery
recanalization by direct thrombectomy 8 h after last proof of good
health. (b) Plain CT 5 h later, showing early cerebellar mass effect.
(c) Plain CT after decompressive posterior craniectomy of 5 cm diameter,
still showing cerebellar mass effect. (d) Plain CT after second
craniectomy on day 3 with enlargement of craniectomy diameter to 7 cm
and partial resection (arrows) of left inferior(D1) and superior(D2)
cerebellar infarcts. Outcome at 3 months, independent, but not
working.Copyright Patrik Michel.Drainage of cerebrospinal fluid by ventriculostomy should be considered in
selected patients in whom the obstructive hydrocephalus is the main cause of
neurological deterioration.
It should be accompanied by suboccipital decompressive craniectomy in
order to avoid deterioration from upward cerebellar herniation.In ICH affecting primarily the cerebellum, clinical deterioration can occur
quickly due to the narrow anatomical space of the posterior fossa, leading to
local mass effect on the brainstem or obstructive hydrocephalus. In such
patients, or patients with cerebellar hemorrhages >3 cm in diameter,
observational studies suggest better outcome with surgical decompression.
Ventricular catheter insertion alone is not recommended
and may actually be harmful, particularly in patients with compressed
cisterns. In contrast to cerebellar hemorrhage, evacuation of brainstem
hemorrhages may be harmful and is not recommended.
Secondary prevention
Stroke recurrence risk
Initially it was suggested posterior circulation TIA and stroke was associated
with a lower risk of recurrent stroke than anterior circulation
disease.( However, prospective natural history studies have shown
it is associated with a high risk of early recurrent stroke, particularly in the
first few weeks.
The stroke subtype with the highest early recurrent stroke risk is
atherosclerotic large artery disease, and the temporal pattern of recurrence is
similar to that seen for carotid artery disease.
Typical sites of posterior circulation atherosclerosis are shown in Figure 4. A pooled
individual patient analysis of two prospective studies in patients with
posterior circulation TIA or stroke, who all had CT- or MR-based angiography to
identify stenosis, reported a 90-day recurrent stroke rate for basilar or
intracranial vertebral stenosis of 33%, compared with 16% for extracranial
vertebral stenosis.( This high early recurrence risk suggests posterior
circulation large artery stenosis should be treated intensively with
antiplatelet agents, as discussed below. It also raises the possibility as to
whether revascularization should be performed, in a similar fashion to
endarterectomy for symptomatic carotid stenosis.
Figure 4.
Frequent sites of atherosclerotic plaques in the posterior
circulation.
PCA: posterior cerebral artery.
Drawing Alexander Salerno.
Frequent sites of atherosclerotic plaques in the posterior
circulation.PCA: posterior cerebral artery.Drawing Alexander Salerno.
Antithrombotic treatment
Medical treatment and risk factor management is similar for both anterior and
posterior circulation stroke. We did not identify trials specifically looking at
prevention of posterior circulation stroke and therefore our recommendations are
based on trials in patients with stroke in all vascular territories. For
non-cardioembolic ischemic stroke, clopidogrel (or aspirin) alone is recommended
for long-term secondary prevention. However, recent studies randomizing patients
to short-term dual antiplatelet therapy with aspirin and clopidogrel immediately
after non-cardioembolic stroke (POINT and CHANCE), showed a lower risk of early
recurrent stroke compared with aspirin alone.
These included posterior circulation stroke but did not separate
treatment effect by vascular territory.It is therefore recommended that patients with recent high-risk minor stroke and
TIA receive dual antiplatelets (aspirin and clopidogrel or aspirin and ticagrelor).
Analysis of the POINT and CHANCE data suggested benefit of dual
antiplatelets for only the first 3 weeks,
so this duration seems reasonable also for the posterior circulation,
before switching to clopidogrel alone. An algorithm for prevention of
posterior circulation ischemic strokes is proposed by the authors in Figure 5, based on
available data.
Figure 5.
Suggested algorithm for prevention of ischemic strokes stratified by the
presence of posterior circulation stenosis.
Rx: treatment; DSA: digital subtraction angiography; INR: interventional
neuroradiologist.
Suggested algorithm for prevention of ischemic strokes stratified by the
presence of posterior circulation stenosis.Rx: treatment; DSA: digital subtraction angiography; INR: interventional
neuroradiologist.Secondary prevention of cardioembolic posterior circulation stroke is as for
anterior circulation stroke. Patients with posterior and anterior circulation
stroke and atrial fibrillation
appear to have similar risks of ischaemic or hemorrhagic events at
90 days. Whether anticoagulation should be started immediately after ischaemic
stroke with atrial fibrillation, or after a period of a week or two, to reduce
risks of hemorrhagic transformation is uncertain and being examined in ongoing
trials such as OPTIMAS
and ELAN (https://www.clinicaltrials.gov/ct2/show/NCT03148457).
Control of cerebrovascular risk factors
The medical arm of SAMMPRIS (Stenting versus Aggressive Medical Therapy for
Intracranial Arterial Stenosis) emphasized the importance of intensive medical
therapy and risk factor control which should be provided to all patients with
posterior circulation stenosis.
We provide intensive statin therapy
to all ischemic stroke patients with or without symptomatic stenosis,
aiming at low-density lipoprotein cholesterol (LDLC) levels <1.4 mmol/L
(<55 mg/L) and a ⩾50% reduction of LDLC when compared to baseline values.
Blood pressure should aim at values below 130/80 mmHg if
tolerated.[41,42] SAMMPRIS and other recent studies also emphasized the
importance of lifestyle interventions including smoking cessation, a healthy
diet, and physical activity. Secondary prevention for ICH in the anterior and
posterior circulations includes lowering of blood pressure to similar values as
after ischemic stroke.
Stenting for symptomatic posterior circulation stenosis
Atheromatous plaques may cause stenosis or occlusion at preferential sites in the
vertebral, basilar, and PCAs (Figure 4). These arteries are surgically less accessible than the
carotid artery, and therefore, although endarterectomy approaches have been used
for vertebral stenosis, they have not been widely adopted.( In
contrast, neurointerventional angioplasty and stenting techniques are used to
treat vertebrobasilar stenoses.
Basilar stenosis
The SAMMPRIS trial randomized 451 patients with recently symptomatic anterior
and posterior circulation intracranial stenosis to either stenting or
intensive medical management including dual antiplatelets with clopidogrel
and aspirin.
The 30-day stroke or death rate was 14.7% in the intervention and
5.8% in the medical group. Beyond 30 days, stroke rates were similar between
both groups. Almost a quarter of patients (22.5% in the medical and 21.9% in
the intervention group) had basilar stenosis. The post-operative risk with
stenting was higher than had been expected, while the risk of recurrent
stroke in patients on intensive medical therapy, lower than predicted.In SAMMPRIS, the outcome was not divided according to location of stenosis,
but findings from a subsequent analysis demonstrated that basilar artery
stenting was associated with a particularly high risk of peri-procedural
ischemic stroke (20.8% versus 6.7% for other arteries), consistent with
other reports that peri-procedural complications from stenting are
particularly high for basilar stenosis. It has been suggested this is
because of the complication of disrupting flow in perforating arteries
arising directly from the basilar artery.It has been suggested the Wingspan stents used in SAMMPRIS may have a higher
complication rate than other stents. However, the VISSIT (Vitesse
Intracranial Stent Study for Ischemic Stroke Therapy) trial, which evaluated
a balloon expandable stent in 112 patients with intracranial stenosis, also
showed a higher stroke rate in the stenting group; the 30-day primary safety
endpoint occurred in 14/58(24%) stented patients compared with 5/53(9.4%) in
the medical group.
VISSIT included basilar stenosis, but the primary paper does not give
outcome by site of stenosis, and we were unable to obtain this information
from the corresponding author.In conclusion, symptomatic basilar artery stenosis should be treated with
intensive medical therapy, and stenting should currently be avoided, mostly
because of the risk of perforator artery occlusions.
Stenting of the VA
Many studies have shown VA stenting is technically feasible, often with an
acceptable complication rate, but these have largely been cases series.
Systematic reviews have reported very low complication rates for
extracranial vertebral stenosis, and 1% or less for origin stenosis, but
higher rates of 5–10% for intracranial vertebral stenosis.[45,46] Such
cases series are open to selection and publication bias, and robust data can
only be provided by RCTs.Five RCTs have assessed effectiveness of angioplasty and stenting in
symptomatic vertebral stenosis. Two of these, SAMMPRIS
and VISSIT,
were confined to intracranial stenosis including basilar and
intracranial vertebral stenoses. Two more recent trials, VIST (Vertebral
Artery Ischemia Trial)
and VAST (Vertebral Artery Stenting Trial),
included only vertebral stenosis, both intracranial and extracranial.
One trial, CAVATAS (Carotid and Vertebral Artery Transluminal Angioplasty
Study) conducted in the 1990s included predominantly carotid artery
stenosis, but also recruited 16 patients with vertebral stenosis.The largest trial was VIST,
which aimed to recruit 540 patients with ⩾50% symptomatic vertebral
stenosis, but recruitment was closed by the funder after 181 patients were
enrolled due to recruitment being slower than expected, a decision which in
retrospect appears unfortunate. Mean follow-up was 3.5 years. Stenosis was
predominantly extracranial (78.7%). The primary endpoint of fatal or
non-fatal stroke occurred in five patients in the stented group versus 12 in
the medical group (hazard ratio: 0.40, 0.14–1.13,
p = 0.08). Therefore, although there was an approximately
60% reduction in the rate of recurrent stroke in patients in the stenting
arm, this difference was not significant. In a post hoc analysis, when time
from randomization was controlled for, which was shorter in the stenting
arm, the hazard ratio for the primary endpoint was significant at 0.34
(0.12–0.98, p = 0.046). The benefit, if any, appeared
higher in patients with extracranial stenosis, in whom the peri-procedural
stroke risk was much lower (0 events, versus 2/13 for intracranial
stenosis).VAST
aimed for a sample size of 180 but recruited 115 of which 83% had
extracranial stenosis. During mean follow-up of 3 years, there were seven
strokes in the medical group and eight strokes in the stenting group. Of the
three early strokes, two occurred in nine patients with intracranial
stenosis (22%), while only 1 (2%) occurred in 48 patients with extracranial
stenosis. The results of VAST were underpowered to detect any treatment
difference, but like VIST showed intracranial stenting had a high
peri-procedural risk.A pooled individual patient data analysis of three of the vertebral stenting
trials (VIST, VAST, and SAMMPRIS) was recently conducted.
Across the three trials, 168 participants (46 intracranial, 122
extracranial) were assigned to medical treatment and 186 (64 intracranial,
122 extracranial) to stenting. Peri-procedural risk was higher for
intracranial than extracranial stenosis (16% versus 1%,
p < 0.001). During 1036 person years of follow-up, the
hazard ratio for any stroke in the stenting group compared with the medical
group was 0.81(0.45–1.44). For extracranial stenosis, it was 0.63
(0.27–1.46), and for intracranial stenosis 1.06 (0.46–2.42). The
Kaplan–Meier curves (Figure 6) show stenting for intracranial stenosis was associated
with a worse outcome, and the difference persisted for a number of years
post-procedure. In contrast, for extracranial stenting, outcomes over the
first year were similar between both arms, with a possible divergence
benefiting stenting at later time points, although sample size was much
reduced at this time.
Figure 6.
Recurrence rates for any stroke in a preplanned pooled individual
patient data analysis of stenting for symptomatic vertebral artery
stenosis: (a) Above, stenting for extracranial stenosis; (b) Below,
stenting for intracranial stenosis. Blue: no stenting. Red: with stenting.
(reprinted with permission).
HR: hazard ratio.
Recurrence rates for any stroke in a preplanned pooled individual
patient data analysis of stenting for symptomatic vertebral artery
stenosis: (a) Above, stenting for extracranial stenosis; (b) Below,
stenting for intracranial stenosis. Blue: no stenting. Red: with stenting.
(reprinted with permission).HR: hazard ratio.In conclusion, there is no definitive data from adequately powered RCTs to
determine whether stenting for symptomatic vertebral stenosis offers benefit
over medical treatment. Available data suggest that with current stenting
techniques, intracranial stenosis is associated with a high peri-operative
risk, and medical treatment is the preferred option. Whether stenting offers
a treatment option for extracranial stenosis remains uncertain. VIST
suggested a possible benefit, particularly in patients operated early after
symptoms.For this reason, we may consider angioplasty and stenting as an option in
recurrent ischemic events from well-documented extracranial vertebral
stenosis, as described in the pragmatic approach described in Figure 5. Further
adequately powered trials of stenting in recent symptomatic extracranial
vertebral stenosis in comparison with optimal medical therapy are required.
In the meantime, aggressive medical treatment of posterior circulation
strokes is of paramount importance.
Authors: Annette Compter; H Bart van der Worp; Wouter J Schonewille; Jan Albert Vos; Jelis Boiten; Paul J Nederkoorn; Maarten Uyttenboogaart; Rob T Lo; Ale Algra; L Jaap Kappelle Journal: Lancet Neurol Date: 2015-04-20 Impact factor: 44.182
Authors: Eelco F M Wijdicks; Kevin N Sheth; Bob S Carter; David M Greer; Scott E Kasner; W Taylor Kimberly; Stefan Schwab; Eric E Smith; Rafael J Tamargo; Max Wintermark Journal: Stroke Date: 2014-01-30 Impact factor: 7.914
Authors: Oliver C Singer; Joachim Berkefeld; Christian H Nolte; Georg Bohner; Hans-Peter Haring; Johannes Trenkler; Klaus Gröschel; Wibke Müller-Forell; Kurt Niederkorn; Hannes Deutschmann; Tobias Neumann-Haefelin; Carina Hohmann; Matthias Bussmeyer; Anastasios Mpotsaris; Anett Stoll; Albrecht Bormann; Johannes Brenck; Marc U Schlamann; Sebastian Jander; Bernd Turowski; Gabor C Petzold; Horst Urbach; David S Liebeskind Journal: Ann Neurol Date: 2015-01-13 Impact factor: 10.422
Authors: Frank L J Visseren; François Mach; Yvo M Smulders; David Carballo; Konstantinos C Koskinas; Maria Bäck; Athanase Benetos; Alessandro Biffi; José-Manuel Boavida; Davide Capodanno; Bernard Cosyns; Carolyn Crawford; Constantinos H Davos; Ileana Desormais; Emanuele Di Angelantonio; Oscar H Franco; Sigrun Halvorsen; F D Richard Hobbs; Monika Hollander; Ewa A Jankowska; Matthias Michal; Simona Sacco; Naveed Sattar; Lale Tokgozoglu; Serena Tonstad; Konstantinos P Tsioufis; Ineke van Dis; Isabelle C van Gelder; Christoph Wanner; Bryan Williams Journal: Eur Heart J Date: 2021-09-07 Impact factor: 35.855
Authors: Richard I Lindley; Joanna M Wardlaw; William N Whiteley; Geoff Cohen; Lisa Blackwell; Gordon D Murray; Peter A G Sandercock Journal: Stroke Date: 2015-01-22 Impact factor: 7.914