Transradial and Transfemoral Approaches for Vertebral Artery Stenting: A Single-Center, Prospective, Non-Inferiority Comparison

Introduction

Vertebral artery origin stenosis (VAOS) has gradually attracted increased attention. Data from the New England Posterior Circulation Stroke Registry indicate that 49% of posterior circulation strokes arise from an artery-to-artery embolic mechanism, but only 16% are considered to be ‘hemodynamically’ related to vertebral artery stenosis [1]. Patients with VAOS who have failed to respond to drug treatment can receive different forms of endovascular treatment, including balloon angioplasty and stent implantation. VAOS stent implantation is associated with a high success rate and a relatively low complication rate [2]. However, we know comparatively little about VAOS compared with carotid artery stenosis [3]. A previous meta-analysis of comparative studies relating to the implantation of intracranial and extracranial vertebral artery stents showed that the complications associated with stent implantation for extracranial vertebral artery stenosis were lower than those associated with stent implantation for intracranial vertebral artery stenosis; thus, VAOS stent implantation may be more beneficial [4].

At present, the classical surgical technique for VAOS stent implantation involves the transfemoral approach (TFA). However, the field of interventional cardiology has progressively adopted the TRA for coronary angiography over the past 3 decades, culminating in a ‘radial first’ strategy, as recommended by the American Heart Association [5]. The transradial approach (TRA) has higher safety and patients do not need bed rest after surgery, it can significantly improve patient comfort, reduce bed-related complications and nursing workload, shorten hospital stay and reduce hospital costs, and it is increasingly used in coronary interventional diagnosis and treatment [6] and neuro-interventional therapy [7]. Compared with TFA, patients with severe intracranial vertebrobasilar stenosis or with a bovine aortic arch or unfavorable arch anatomy, the TRA was shown to be a safe and feasible alternative route of access [8,9]. Zoltan et al performed a randomized controlled trial to investigate the safety and efficacy of carotid artery stent implantation via the radial-artery approach as compared to the femoral artery approach. They found that radial-artery access for carotid stenting resulted in comparable rates of major adverse events and rare vascular complications, while yielding shorter hospital stays. Based on these findings, Zoltan et al recommended that the radial-artery pathway should be considered the preferred option for patients with type II and III aortic disease and severe peripheral artery disease (PAD) [10]. However, there are few published reports on the safety and feasibility of transradial treatment for vertebral artery stenting. We believe that the origin of the vertebral artery is situated at the initial segment of the subclavian artery, distal to the carotid artery, and in patients with type II and III aortic disease, transfemoral access can be associated with technical challenges that impede successful navigation into the target vessel. Therefore, in this study, we assessed whether a transradial approach is a safe and effective route for VAOS stent placement. In addition, we subdivided the TRA group to ipsilateral TRA group and contralateral TRA group to explore whether the ipsilateral TRA can reduce the difficulty of stent placement, the risk of embolization, and the time from sheath insertion to stent insertion for patients with bovine arch and type II and III aortic arch, and whether it can improve the success rate.

Material and Methods

INCLUSION CRITERIA:

The inclusion criteria were: (1) aged 18–80 years; (2) cases of asymptomatic VAOS failing to respond to the best drug treatments; (3) mRS grade of 3 or less; (4) NIHSS score ≤6, and (5) angiography showing target lesion stenosis ≥70%.

EXCLUSION CRITERIA:

The following exclusion criteria were applied: (1) patients with a tendency for severe bleeding, intracranial or extracranial bleeding, and active gastrointestinal ulcers within the past 3 months; (2) drug intolerance (contrast media, aspirin, or clopidogrel); (3) patient’s in a generally poor condition, including uncontrolled malignant hypertension, serious medical diseases, and malignant tumors; (4) poor blood vessel conditions, including vascular distortion and variation; and (5) patients with special vascular lesions, including acute large vessel occlusion, emergency intracranial angioplasty, restenosis after stent implantation, nonatherosclerotic arterial stenosis, and continuous distal stenosis of the stenotic segment or distal vascular dysplasia.

OPERATOR EXPERIENCE:

Our institution, an academic cerebrovascular center, has been conducting cerebrovascular interventions for 20 years, and our team of physicians has performed approximately 3000 neurovascular procedures. Prior to involvement in this study, each operator had independently completed at least 30 (range, 30–158) radial access angiograms and 100 femoral access angiograms.

PROCEDURE:

A 6-Fr (90 cm) Envoy Guiding Catheter (Cordis, Miami Lakes, FL, USA) was advanced to the subclavian artery at the origin of the vertebral artery. The TFA was then pushed to the proximal end of the subclavian artery, and the TRA was pushed to the distal end of the subclavian artery. We used transradial telescoping catheter technique with a distal access catheter and Simmons catheter to establish the transradial approach. The angle between the arteries is usually too sharp to enter, especially when there is a type - aortic arch or bovine aortic arch. By selecting the appropriate type of Simmons catheter and twisting the Simmons catheter over the aortic arch, it can usually enter into the target blood vessel. Next, 0.014–200 cm Fathom Steerable Guidewires (Boston Scientific) were super-selected to enter the vertebral artery beyond the V2 segment of the stenosis, and the balloon-expanded stent was selected according to the measurement and then was inflated to below the nominal pressure. We used bare-metal stents, such as the Herculink elite (Herculink, Abbott Vascular, USA) or Apollo (MicroPort Medical, Shanghai, China) and drug-eluting stents such as the Bridge (MicroPort Medical, Shanghai, China) or Maurora (Litai letter Medical, Shanghai, China). To expand and implant stents, we used a 2.0-mm Sprinter Rapid Exchange Balloon Dilatation Catheter (MicroPort Medical, Shanghai, China) with a residual lumen diameter <1.5mm.

MEDICAL THERAPY:

Patients received antiplatelet therapy with aspirin enteric-coated tablets (100 mg/day) combined with clopidogrel tablets (75 mg/day) for at least 5 days prior to surgery and CYP2C19 gene metabolic testing. Previous analyses have shown that Asian stroke patients or TIA patients who carry the CYP2C19LoF alleles and are taking clopidogrel are at a significantly higher risk of recurrent ischemic stroke than non-carriers [13–15]. The Food and Drug Administration (FDA) also updated the label information of clopidogrel with a suggestion to consider an alternative antiplatelet for patients identified as poor metabolizers of CYP2C19. So, for patients with intermediate or low metabolic clopidogrel, therapy was adjusted to cilostazol tablets (100 mg twice daily) for at least 3 days. Heparinization (0.5–0.6 mg/kg) was performed during the procedure, and half the dose was given after 1 h if required. Three months after bare-metal stent implantation, the patient received dual antiplatelet therapy, statin therapy, and reasonable control of blood pressure.

FOLLOW-UP AND OUTCOMES:

The outcomes were intraoperative digital subtraction angiography (DSA) degree of stenosis, stenting success during surgery, intraoperative changes in the path ratio, appropriate placement of the guiding catheter until the end of surgery, and the postoperative and discharge time. Patients were followed up at 1, 3, and 6 months, and 1 year after surgery through outpatient examination and telephone calls. Complications included stroke, TIA, and all vascular-related deaths recorded within 30 days after the intervention. At 6 months after the operation, vertebral artery ultrasound was used to determine whether restenosis was present. Restenosis was defined as the presence of restenosis in the implanted stent or adjacent to the bracket (5 mm) with a stenosis lumen diameter greater than 50% [16,17].

The primary safety endpoint was any form of stroke or death within 30 days of surgery. The secondary outcomes were the technical success of stent placement (defined as a post-intervention stenosis <30%), symptomatic in-stent restenosis (ISR) within 1 year (defined as ISR related to an ischemic event in the affected region); ischemic stroke in the target vessel territory between day 31 and 1 year; serious adverse events; any form of intracranial hemorrhage, including intracerebral, subarachnoid or intraventricular hemorrhage; death; or TIA. We also analyzed the NIHSS score and mRS score at 1-year follow-up.

STATISTICAL ANALYSIS:

Categorical variables are presented as absolute and relative frequencies. The normality of the continuous variables was tested by the Shapiro-Wilk test, in which data with normal distribution are described as mean±standard deviation, otherwise as median and interquartile range (IQR). Categorical variables are presented as numbers and percentages. One-way analysis of variance (ANOVA) was performed to assess the data with normal distribution, while the Kruskal-Wallis ANOVA on ranks was used for categorical variables and variables following skew distribution. Post hoc analyses were implemented when appropriate with the Bonferroni’s post hoc test. To compare categorical variables, we used the χ² test, except for when the expected frequencies in contingency tables were <5, in which case Fisher’s exact test was utilized. P<0.05 was considered to indicate statistical significance. Data were analyzed using SPSS version 27 (International Business Machines Corp., Armonk, NY, USA.).

Results

STUDY PARTICIPANTS:

We included 102 patients (age range, 44–80 years) in analyses. No patients changed groups before surgery. Intraoperatively, we had 2 patients in the TFA group who could not tolerate the pain and were converted to the ipsilateral radial-artery path. One patient in the contralateral TRA group was converted to the ipsilateral TRA due to the presence of a type II and III aortic arch that caused problems accessing the contralateral vertebral artery (Figure 1). When comparing the 3 groups, we found that the age, sex, underlying diseases (hypertension, diabetes, coronary heart disease, hyperlipidemia), smoking, mRA score, and NIHSS score at admission were similar (Table 1).

PRIMARY OUTCOMES:

The times from sheath insertion to stent placement were significantly different among the 3 groups (P<0.01); it was much shorter in the ipsilateral TRA group (median time: 19 min; IQR: 12–24.5 min) when compared with the TFA group (median time: 29 min; IQR: 21–35.5 min; P<0.01; 95% CI: 10 min [6–14 min]). There was no significant difference between the contralateral TRA group (median time: 20.5 min; IQR: 13.25–39.5 min) and the TFA group (median time: 29 min; IQR: 21–35.5 min; P=0.588), but the mean median time in the contralateral TRA group was shorter than in the TFA group (Table 2).

Furthermore, the time from surgery to discharge were also significantly different among the 3 groups (P<0.01). The time from surgery to discharge in the ipsilateral TRA group (median time: 4 days; IQR: 3–5 days) was significantly shorter than in the TFA group (median time: 6 days; IQR: 5–7 days; P<0.01; 95% CI: 2 days [2–3 days]). And there was also have significance between the contralateral TRA group (median time: 3.5 days; IQR: 2.25–4 days) and the TFA group (median time: 6 days; IQR: 5–7 days; P<0.01) (Table 3).

Compared with the ipsilateral TRA group and the contralateral TRA group, there was no significant difference in the proportion of intraoperative path changes in the TFA group (P=0.184). Furthermore, there was no significant difference between the groups with regards to the success rate of stent placement (P=1.000) (Table 4).

SECONDARY OUTCOMES:

No strokes were recorded within 30 days in the TFA group, ipsilateral TRA group, and contralateral TRA group. There were 4 cases of TIA in the TFA group, 3 cases in the ipsilateral TRA group, and 1 case in the contralateral TRA group (P=0.725). After 6 months, ultrasound was used to check for restenosis in the vertebral artery; 4 patients in the TFA group were not followed up, 2 patients refused examination, and 8 patients (15.1%) had restenosis. In the ipsilateral TRA group, 3 patients were not followed up, 2 patients refused examination, and 6 patients (14.6%) had restenosis. In the contralateral TRA group, 1 patient refused examination and 1 patient (12.5%) had restenosis; there was no significant difference among the 3 groups (P=0.981). In addition, we recorded any cases involving symptomatic ISR within 1 year in the 2 groups, ischemic stroke in the target vessel territory within 1 year, intracranial hemorrhage within 1 year (including intracerebral, subarachnoid, or intraventricular hemorrhage), and death within 1 year. There was no significant difference among the 3 groups in this respect (Table 4).

PATIENT SATISFACTION:

The patient satisfaction survey tool was utilized by all enrolled patients prior to discharge, resulting in a questionnaire recovery rate of 100%. A 7-question patient satisfaction survey was developed based on relative reviews and original studies, including access site pain after sheath insertion, sheath removal, postoperative bed time, back pain after operation, and embarrassment, anxiety, and overall discomfort. Surveys were used to assess patients’ attitudes and experiences by asking general questions regarding comfort, feasibility, and acceptability, with responses scored on a 1–5 Likert scale, with 1 being strongly disagree and 5 being strongly agree. Surveys were provided before discharge, and all patients completed the survey. This questionnaire task was completed by an impartial central administrator, our head nurse, who was not involved in the subsequent analysis.

In the TFA group, 48 patients (90.6%) favored the ipsilateral radial-artery approach. In the ipsilateral TRA group, 37 patients (90.2%) expressed a preference for continuing with the ipsilateral radial-artery approach for stent implantation at the origin of the ipsilateral vertebral artery. Of the 7 patients in the contralateral TRA group (87.5%), there was a tendency toward utilizing the radial-artery path; however, these patients did not specify whether this should have involved an ipsilateral or contralateral approach due to specific decisions made by physicians based on pathological changes, topological structure, and the type of aortic arch, to ensure appropriate choices were made. Patient satisfaction significantly favored radial access over femoral access in terms of pain after sheath insertion and removal, and discomfort before discharge, including back pain, embarrassment, and anxiety levels. Patients who underwent radial access experienced notable improvements in both acceptance and postoperative recovery when compared to those who received femoral access.

Discussion

LIMITATIONS:

An important limitation of the present study was that as surgery was involved and patients needed to sign informed consent, researchers and participants could not be blinded, which may result in performance bias of research results. Small radial artery diameter and abnormal development are important causes of TRA failure, and it is recommended that radial artery diameter ≥2.3 mm to perform TRA is safer [22,23]. Chun et al recommended routine pre-operation radial ultrasound to predict radial artery diameter [24]. In our study, ultrasound examination was not performed routinely, but the Allen test was used before surgery, which may also have led to bias in the study results. Another limitation is that we did not perform subgroup analysis of our patients according to the type of arch in the radial artery. Further limitations relate to the small number of patients undergoing contralateral TRA, and the loss of follow-up at 6 months and 1 year, which may also have led to bias. Future research needs to involve a large cohort of patients in multiple centers.

Conclusions

This prospective and comparative study directly compared the TFA and the ipsilateral radial approach with the contralateral radial approach for stenting in patients with VAOS and confirmed equivalent levels of patient efficacy and patient safety, with a shorter procedure time and postoperative time to hospital discharge. Furthermore, we demonstrated higher levels of patient satisfaction with the ipsilateral radial approach. We hope that our findings can prompt medical institutions to adopt the ipsilateral radial-artery approach for stent implantation to treat VAOS and provide a basis for future research.