Safety and Efficacy of Distal Embolic Protection Device in Vertebral Artery Origin Stenting
Safety and Efficacy of Distal Embolic Protection Device in Vertebral Artery Origin Stenting
This is a prospective single-center,randomized controlled trial,aiming to investigate the
 safety and efficacy of distal EPD in vertebral artery origin stenting(VAOS);256 subjects will
 be recruited in this study,after randomized recruitment, treatment group(128 subjects each
 group) undergo VAOS with adjuvant distal embolic protection device（EPD）,control group undergo
 routine VAOS without distal embolic protection device.Intraprocedural and postprocedural
 in-hospital adverse events,including stroke,death and dis-retrieval of EPD,will be noted and
 cost-effectiveness analysis also will be conduct,including economic cost,hospital stays.
Ischemic cerebrovascular diseases are associated with a high rate of mortality and disability
 rate, as a consequence, many related trials were conducted to perfect prophylaxis and
 treatment of ischemic stroke. 2/3 of cerebral blood supply is offered by Internal carotid
 artery(ICA) , due to high morbility and disability rate of carotid territory stroke, stoke
 caused by ICA stenosis is always emphasized by authors. With the development to the depth in
 this field, ischemic stroke in posterior circulation related to vertebral artery stenosis is
 gradually paid attention recently. Outcome from New England medical center posterior
 circulation registry study revealed that 20% of patients were found to have vertebral artery
 origin(VAO) stenosis, in 9% of these patients, no other cause of stroke was identified. The
 relative risk of having a stroke or dying in patients with VAO stenosis was 6 times than that
 of patients without VAO stenosis. Therefore, VAO stenosis need appropriate management to
 prevent potentiality of ischemic stroke.

 Nowadays there are three treatment alternatives for extracranial VAO stenosis: medicine,
 surgery and endovascular stent angioplasty. However, medical therapy mainly focus on
 prevention and delay of severe ischemic events other than radical therapy, and it's not
 always effective to improve symptoms of posterior circulation ischemia. Surgery are limited
 by its serious trauma and the combined postoperative morbidity and mortality rates ranging
 from 10% to 20%.Endovascular stent angioplasty was feasible in ICA stenosis as reported in
 literatures, and that promotes the utilization of stent in VAO stenosis in recent years.
 Related retrospective studies have demonstrated the safety and efficacy of vertebral artery
 origin stenting(VAOS) in VAO stenosis. In a Meta analysis that summarized 27 articles about
 extracranial vertebral artery stenting, Stayman observed that the rate of transient ischemic
 attack(TIA) and stroke within postprocedural 30 days was 1.1% and 0.8% respectively. Compter
 etc. are conducting a prospective case-control study to assess the safety and feasibility of
 VAOS, which final outcome is thought to be relatively authentic.

 However, some drawbacks in VAOS needs additional resolution, like embolization caused by
 plaque debris, high restenosis rate, vasospasm, vessel dissection. Especially, embolization
 is associated with not only plaque characteristic, but also anatomy of the vertebral
 arteries, which is potentially essential to high risk of plaque debris dislodgment. The
 origin of vertebral artery is characterized with small diameter and tortuous course. Dodevski
 analyzed 30 patients' vertebral arteries and found that 40% of patients' vertebral artery was
 tortuous, the diameter of the VAO on the left side was in the range between 1.60-5.2 mm, mean
 3.33 ± 0.89 mm, and on the right side from 1.64-5.40 mm, mean 3.19 ± 0.98 mm. Tortuosity and
 small diameter in VAO will increase operation difficulty and procedural time.
 Borhanisummarized 27 articles focusing on vertebral origin angioplasty and concluded that of
 the 808 patients underwent stent angioplasty, the combined rate of stroke and TIA within 1
 month after stenting was 6.9%.

 Concerning dislodgement of plaque debris, embolic protection device(EPD) is applied recently
 to decrease the risk of embolization. But utilization of EPD in VAOS is mainly based on its
 safety and feasibility in carotid artery stenting(CAS). In CAS, cerebral embolic protection
 devices can effectively reduce the incidence of transient ischemic attack, stroke and other
 related adverse events. The U.S. Safety Committee recommended stopping unprotected CAS,
 because the 30-day rate of stroke was 3.9 times higher than that of CAS with cerebral
 protection. However, VAOS is different from CAS, and its performance in CAS cann't serve as
 medical science evidence for distal EPD in VAOS. Firstly, the rate of postoperative
 restenosis after VAOS is higher than that of CAS, ranging from 20% to 66.7%.Secondly, VAO are
 characterized by concentric, fibrous, and smooth lesions with lower incidence of ulceration
 and intraluminal hemorrhage compared with extracranial carotid artery circulation[13].
 Thirdly, the microscopic structure of VAO is featured with elastic fibers and smooth muscles.
 These distinctions indicate that investigators should make a distinction between CAS and VAOS
 in terms of intravascular intervention. As to the use of EPD in VAOS, no Class Ⅰ evidence can
 verify the safety and efficacy of EPD and clinicians share discrepant opinions. Some authors
 thought that distal protection devices will suspend operation process, increase
 operation-related risk and may cause embolization during crossing lesion and retrieval which
 may be referable to transient shear stress. In addition, some patients are intolerable to
 flow cessation caused by distal EPD. Moreover, foreign case reports even noted that
 utilization of distal EPD was probable to induce vasospasm and difficult retrieval of distal
 EPD was finally managed by secondary surgery in some cases[14, 15]. However, small
 sample-size studies demonstrated it's safe and feasible to use distal EPD in VAOS. Qureshi
 etc.retrospectively analyzed clinical data of 12 patients underwent VAOS with filter
 protection, outcome revealed that no stroke and death events occured within 1 month
 follow-up. In a multicenter study, Edgell etc. contrastively analyzed the data of patients
 underwent VAOS with and without distal EPD, the rate of TIA and stroke within 1 month between
 the two groups showed no significant difference. Divani etc. analyzed plaque debris captured
 by EPDs in 14 patients who underwent VAOS with distal protection devices, the outcome
 revealed that relative to the size of the filter, the proportion of captured debris ranged
 from 0.1% to 22% in the VA filters, hence, Divani recommended the use of distal EPD in VAOS.

 In summary, the use of distal EPD in VAOS is debatable, no class I evidence can support the
 advantage of use of distal EPD in VAOS. Here, the investigators will conduct this
 prospective, single-center, randomize controlled trial aiming to analyzed the safety and
 efficacy of distal EPD in VAOS.
Inclusion Criteria:

 1. Aged 40 to 80 years old;

 2. VAO atherosclerotic stenosis results in posterior circulation ischemic symptom
 refractory to best medical treatment;

 3. symptomatic VAO atherosclerotic stenosis>70% evaluated by computed tomograph
 angiography(CTA) or Magnetic Resonance Angiography(MRA) or digital subtraction
 angiography(DSA);

 4. the diameter of the normal segment of the artery beyond the stenosis >3.5mm;

 5. written informed consent.

 Exclusion Criteria:

 1. VAO stenosis is combined with ipsilateral vertebrobasilar disease including severe
 cranial vertebral artery stenosis and severe basilar artery stenosis.

 2. VAO is occluded;

 3. Patients who will be underwent bilateral VAOS due to bilateral VAO stenosis including
 someone with bilateral VAO stenosis >70% and the patient who need contralateral VAOS
 after stenting in unilateral VAO due to recurrent posterior circulation ischemia
 refractory to best medical treatment.

 4. VAO stenosis caused by arteritis,artery dissection, aplasia, vasculopathy caused by
 radiotherapy etc, other than atherosclerosis;

 5. stroke within 30 days or myocardial infarction within 6 months;

 6. contraindication of anticoagulant and antiplatelet agents; allergy to iodinated
 contrast agent;

 7. severe comorbid diseases and intolerant to procedure; patient unlikely to cooperate
 with the procedure or provide informed consent.

 8. High risk of difficulty or failure in EPD advance and retrieval due to the tortuosity
 of the culprit vertebral artery origin.