Endovascular Treatment for Acute Posterior Circulation Tandem Lesions: Insights From the BASILAR and PERSIST Registries
Article information
Abstract
Background and Purpose
Limited evidence exists on the effectiveness of endovascular treatment (EVT) for acute posterior circulation tandem lesion (PCTL). This study aimed to explore the role of extracranial vertebral artery (VA) stenting in patients with PCTL stroke undergoing EVT.
Methods
Individual patient data were pooled from the BASILAR (EVT for Acute Basilar Artery Occlusion Study) and PERSIST (Posterior Circulation Ischemic Stroke) registries. Patients with PCTLs who underwent EVT were included in the present cohort and divided into the stenting and nonstenting groups based on the placement of extracranial VA stents. The primary efficacy outcome was the modified Rankin Scale (mRS) scores at 90 days and 1 year. Safety outcomes included 24-hour symptomatic intracranial hemorrhage (sICH) and all-cause mortality at 90 days and 1 year post-surgery.
Results
A combined dataset of 1,320 patients with posterior circulation artery occlusion, including 263 (19.9%) with tandem lesions, of whom 217 (median age, 65 years; 82.9% male) met the inclusion criteria for the analysis. The stenting group had 84 (38.7%) patients, while the non-stenting group had 133 (61.3%). After adjustment for the potential confounders, extracranial VA stenting was associated with favorable shifts in mRS scores at both 90 days (adjusted common odds ratio [OR], 2.30; 95% confidence interval [CI], 1.23–4.28; P<0.01) and 1 year (adjusted OR [aOR], 2.04; 95% CI [1.05–3.97]; P=0.04), along with lower rate of mortality at both 90 days (aOR, 0.45; 95% CI [0.21–0.93]; P=0.01) and 1 year (aOR, 0.36; 95% CI [0.16–0.79]; P=0.01), with no significant difference in sICH incidence (aOR, 0.35; 95% CI [0.06–1.98]; P=0.24).
Conclusion
Extracranial VA stenting during EVT may improve functional outcomes and reduce mortality in patients with PCTL strokes.
Introduction
Recent randomized clinical trials (ATTENTION [Endovascular Treatment for Acute Basilar-Artery Occlusion] and BAOCHE [Basilar Artery Occlusion Chinese Endovascular Trial]) in China have demonstrated the safety and efficacy of endovascular treatment (EVT) for patients with posterior circulation large vessel occlusion [1,2]. Posterior circulation tandem lesion (PCTL) is defined as a concomitant posterior circulation artery occlusion (PCAO) with severe stenosis (≥70%) or occlusion in the extracranial vertebral artery (VA), specifically in V1, V2, or proximal V3 segments [3]. PCTL occurs in 25%–29% of patients with acute posterior circulation stroke [4]. The treatment of tandem lesions represents a considerable challenge. There is little data on PCTLs, but in anterior circulation tandem lesions standard intravenous (IV) thrombolysis alone achieves recanalization in only 4% to 32% of cases, with good functional outcomes limited to only 17% of cases and with a death rate as high as 55% [5]. Patients with PCTL were excluded from most of the randomized controlled trials [1,2,6,7]. Therefore, despite the growing evidence supporting EVT for anterior circulation tandem occlusions, there is paucity of data regarding EVT in PCTL.
There are distinct anatomic considerations, including the dominance pattern of the VAs and the greater potential for collateral anastomosis, that preclude the extrapolation of EVT data from anterior to posterior circulation tandem occlusions [8]. While some recent studies have shown that EVT for PCTL is both safe and feasible [9-14], there is currently no consensus about the ideal technical strategies for tandem lesions, with uncertainties surrounding which of the two VAs to approach (e.g., the “clean- vs. dirty-road” approaches) as well as which recanalization strategy to use for the extracranial steno-occlusive lesion. The treatment for extracranial VA varies from no intervention to acute angioplasty with or without stenting. Given these challenges, this study aims to compare strategies for extracranial VA lesions in patients undergoing EVT for acute ischemic stroke (AIS) due to PCTL, using data from two large multicenter prospective registries.
Methods
Patients and study design
This post hoc analysis pooled data from two observational studies: the BASILAR (EVT for Acute Basilar Artery Occlusion Study; http://www.chictr.org.cn; ChiCTR1800014759) and PERSIST (Posterior Circulation Ischemic Stroke; http://www.chictr.org.cn; ChiCTR2000033211) registries, previously described in detail. Briefly, BASILAR prospectively recruited patients treated with EVT at 47 comprehensive stroke centers across 15 provinces in China from January 2014 to May 2019 [15]. PERSIST, a retrospective multicenter registry, included patients treated with EVT at 21 stroke centers in China from December 2015 to December 2018 [16]. The inclusion criteria for the current analysis were: (1) age ≥18 years, (2) presentation within 24 hours of PCTL onset, (3) presence of PCTL confirmed by computed tomography angiography, magnetic resonance angiography, or digital subtraction angiography; (4) use of EVT with contemporary technology including stent retriever and/or contact aspiration catheters.
PCTL was defined as an intracranial occlusion involving the intracranial VA, the proximal (from the vertebrobasilar junction to the origin of the anterior inferior cerebellar artery), middle (from the origin of the anterior inferior cerebellar artery to the origin of the superior cerebellar artery), or distal (distal to the origin of the superior cerebellar artery) basilar artery, or the posterior cerebral artery, and an extracranial VA steno-occlusive lesion (stenosis ≥70% or complete occlusion, as defined by North American Symptomatic Carotid Endarterectomy [NASCET] Trial) [17]. The neurointerventional approach of extracranial VA was based on the operator’s preference and included extracranial VA stenting with/without angioplasty (stenting group) or EVT without extracranial VA stenting (non-stenting group). The non-stenting group included patients who did not undergo EVT for extracranial VA lesions or who were treated with angioplasty alone. Given the retrospective study design and use of de-identified data, this study was approved under a waiver of informed consent by the local institutional review boards at each participating center (BASILAR 2013-087-01; PERSIST 2020 KY-40) and was reported in accordance with the Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) guidelines.
Outcome measures
The primary efficacy outcome was the modified Rankin Scale (mRS) score at 90 days and 1 year, ranging from 0 (no residual symptoms) to 6 (death), with 3 indicating moderate disability but independent walking, assessed by blinded local neurologists. The secondary clinical efficacy outcome was the rate of favorable functional outcomes (mRS scores of 0–3) at 90 days and 1 year. Technical efficacy was measured by the rate of successful revascularization, defined as a modified Thrombolysis in Cerebral Infarction (mTICI) score of 2b or 3, indicating reperfusion of ≥50% of the affected vascular territory. Safety outcomes included symptomatic intracranial hemorrhage (sICH) within 24 hours and all-cause mortality at 90 days and 1 year, with intracranial hemorrhage classified according to the Heidelberg Bleeding Classification [18]. Procedural complications included vessel perforation, arterial dissection, distal embolization, and vasospasm.
Antiplatelet management
To prevent thrombosis after stent implantation and reocclusion of residual stenosis, IV tirofiban (a glycoprotein IIb/IIIa inhibitor) was administered. If stent implantation during the operation was necessary, tirofiban was administered 5 minutes before stent deployment. Continuous tirofiban infusion at 2/3 of the recommended cardiac dose was started after excluding any significant hemorrhagic complications, with a post-procedure head computed tomography (CT) performed immediately after the procedure and continued for 24 hours. The patients were subsequently administered clopidogrel and aspirin after excluding any significant intracranial hemorrhage (ICH) on repeat head CT at 24 hours. Tirofiban infusion was stopped 6 hours after aspirin and clopidogrel loading, and regular doses of aspirin (100 mg) and clopidogrel (75 mg) were administered starting the following day.
Statistical analysis
Data are presented as medians (interquartile range [IQR]) or frequencies with percentages unless otherwise indicated. Univariate analysis was performed using the Mann-Whitney U test, χ2 test, or Fisher exact test, as appropriate. The effect size of the primary outcome was adjusted for the common odds ratio (cOR) and estimated using multivariable ordinal logistic regression. The effect size of other outcomes was adjusted for odds ratios (ORs) and calculated using multivariable binary logistic regression. Unadjusted and adjusted effect sizes are reported with 95% confidence intervals (CI) to indicate statistical precision. Age, diabetes mellitus, hyperglycemia, current smoking status, presence of atrial fibrillation, baseline National Institutes of Health Stroke Scale (NIHSS) score, baseline posterior circulation Acute Stroke Prognosis Early CT Score (pc-ASPECTS), first-line treatment, and postoperative IV tirofiban use were included in the multivariable regression models. Statistical testing was done at the 2-tailed α-level of 0.05. Data were analyzed using R version 3.3.3 (R Foundation for Statistical Computing, Vienna, Austria).
Results
Baseline and procedural characteristics
The combined dataset yielded 1,320 patients with PCAO treated with EVT across the two registries (BASILAR, n=647; PERSIST, n=673), including 263 (19.9%) patients presenting with tandem lesions (110 from BASILAR and 153 from PERSIST). Among the 263 tandem patients, 217 (median [IQR] age, 65 [56–73] years; baseline NIHSS score, 23 [13–30]; baseline pc-ASPECTS, 9 [7–10]; 180 men [82.9%]) met the study criteria and were included in the final analysis (Figure 1). A total of 84 (38.7%) and 133 (61.3%) patients were included in the stenting and non-stenting groups, respectively. Overall, 52 (24.0%) patients received intravenous thrombolysis (IVT) before the endovascular procedure, and 133/216 (61.6%) were treated under general anesthesia. The first-line mechanical thrombectomy technique was the stent retriever alone in 73.3% (159/217), combined stent retriever and contact aspiration in 21.2% (46/217), and contact aspiration alone in 5.5% (12/217) of the cases (Table 1).
Flowchart of patient selection. EVT, endovascular treatment; BASILAR, EVT for Acute Basilar Artery Occlusion Study; PERSIST, Posterior Circulation Ischemic Stroke; MT, mechanical thrombectomy; IA, intra-arterial.
Baseline characteristics according to the use of extracranial vertebral artery stent in the overall cohort
Compared with the non-stenting patients, stenting patients were younger (63 [53.5–68] vs. 66 [57–75] years, P=0.04), had a lower rate of atrial fibrillation (3.6% vs. 15.8%, P=0.02), and had a higher proportion of IV tirofiban use (55/77 [71.4%] vs. 58/104 [55.8%], P=0.03). The median NIHSS scores at baseline (24.5 [15–30.5] vs. 23 [12–30], P=0.49) and IVT rates (16 [19.1%] vs. 36 [27.1%], P=0.19) were similar between the two groups. In the stenting group, intracranial occlusion was more often treated with a stent retriever alone as the first-line treatment (81.0% vs. 68.4%, P=0.02), whereas the combined technique was more often used in the non-stenting group (11.9% vs. 27.1%, P=0.02). The time from puncture to recanalization was 25 minutes longer in the stenting group than in the non-stenting group (140 [105–176] vs. 115 [80–175] minutes, P=0.03). Other baseline and procedural characteristics were not significantly different between the two groups (Table 1).
Primary efficacy outcome
After adjusting for age, diabetes mellitus, hyperglycemia, current smoking, presence of atrial fibrillation, baseline NIHSS score, baseline pc-ASPECTS, first-line treatment, and postoperative IV tirofiban use, there was a significant improvement in the distribution of the mRS score at both 90-days (adjusted cOR, 2.30; 95% CI, 1.23–4.28; P<0.01) and 1 year (adjusted OR [aOR], 2.04; 95% CI, 1.05–3.97; P=0.04) favoring the stenting group (Table 2 and Figure 2).
Comparisons in clinical and procedural outcomes according to the use of extracranial vertebral artery stent in the overall study sample (main analysis)
Distribution of modified Rankin Scale (mRS) score at 90 days between the stenting and non-stenting groups (mRS ordinal shift: adjusted common odds ratio 2.08, 95% confidence interval [1.09–3.95], P=0.03).
Secondary efficacy outcomes
The secondary clinical and technical efficacy outcomes of recanalization are shown in Table 2 and Figures 2 and 3. The rate of favorable outcomes (mRS score ≤3) at 90 days and 1 year was 39.5% (85/215) and 41.2% (86/209) for all patients with PCTL, respectively. The proportion of favorable outcomes (mRS score ≤3) at 90 days (37/84 [44.1%] vs. 48/131 [36.6%]; aOR: 2.47 [95% CI, 1.04–5.89]; P=0.04) was significantly higher in the stenting than in the non-stenting group. However, no statistically significant differences were observed at 1 year (35/81 [43.2%] vs. 51/128 [39.8%]; aOR: 1.50 [95% CI, 0.64–3.52]; P=0.35). Although not statistically significant, there was a trend toward a higher rate of successful recanalization in the stenting group compared with the non-stenting group (78/84 [92.9%] vs. 112/133 [84.2%]; aOR: 2.53 [95% CI, 0.88–7.31]; P=0.09).
Distribution of modified Rankin Scale (mRS) score at 1 year between the stenting and non-stenting groups (mRS ordinal shift: adjusted common odds ratio 1.81, 95% confidence interval [0.95–3.46], P=0.07).
Safety outcomes
The rate of mortality was significantly lower in the stenting as compared to the non-stenting patients at both 90 days (29/84 [34.5%] vs. 57/131 [43.5%]; aOR: 0.45 [95% CI, 0.21–0.93]; P=0.01) and 1 year (32/81 [39.5%] vs. 67/128 [52.3%]; aOR: 0.36 [95% CI, 0.16–0.79]; P=0.01). The rate of sICH was 3.6% (3/84) in the stenting and 9.2% (12/131) in the non-stenting (aOR: 0.35 [95% CI, 0.06–1.98]; P=0.24) group (Table 2). Device-associated or procedural complications were observed in 31 patients (14.3%), with no significant differences in the rates of arterial perforation, dissection, distal embolization, vasospasm, or vascular rupture between the two groups. The rates of other serious adverse events during the 90-day follow-up period were similar between the two treatment groups (Table 1).
Discussion
To the best of our knowledge, the current analysis represents the largest study of consecutive patients who underwent EVT for acute symptomatic PCTL. The primary findings of our study are as follows: First, tandem lesions are relatively common in the posterior circulation, representing approximately one-fifth of all acute PCAO; Second, given the overall comparable baseline characteristics and outcomes to what has been reported in the recent randomized controlled trials (RCTs) of non-tandem PCAO, patients with AIS and confirmed acute symptomatic PCTL appear to benefit with respect to functional recovery when EVT is administered within 24 hours of estimated occlusion time; Third, compared with no extracranial VA stenting, treatment with acute extracranial VA stenting seems to be associated with better functional outcomes and lower mortality rate at 90 days without increasing the risk of sICH.
In the present study, PCTLs accounted for 19.9% of all posterior circulation large vessel occlusions, which is consistent with the available literature on posterior circulation tandem occlusions (approximately 25%–29%) [3,11,12,19,20] and comparable to what is observed in the anterior circulation (17%–32%) [21-23]. PCTLs frequently lead to severe strokes, yet they remain a poorly understood subtype of acute posterior circulation strokes [24]. Currently, literature on the outcomes of EVT for PCTL patients is limited, predominantly from single-center studies. The reported mortality rates ranged from 20% to 42.9%, with only 28.6% to 53.3% of patients achieving functional independence (mRS 0–2) [9-12,25-27]. Notably, the rate of favorable outcomes (90-day mRS 0–3) in our PCTL population (39.5%) was comparable to that observed in the BEST (Endovascular Interventions Versus Standard Medical Treatment), BASICS (Basilar Artery International Cooperation Study), ATTENTION, and BAOCHE RCTs of non-tandem PCAOs (42%, 44.2%, 46%, and 46%, respectively). Similarly, the rate of successful recanalization (mTICI 2b-3) in our PCTL cohort (87.6%) aligned with the rates reported in non-tandem PCAO RCTs (71%, 72%, 93%, and 88%). Furthermore, the rates of sICH (7.0% vs. 8%, 4.5%, 5%, and 9%) and 90-day mortality (40.0% vs. 33%, 38.3%, 37%, and 31%) were also consistent with data from non-tandem PCAOs trials [1,2,6,7]. These findings suggest that EVT for acute PCTL may be beneficial with an acceptable safety profile.
Our findings are also consistent with several previously published studies of anterior circulation tandem occlusions that reported clinical outcomes favoring acute stenting in tandem lesions [28-31]. Patients in the stenting group were significantly younger and had a lower rate of atrial fibrillation than those in the non-stenting group. These factors may have influenced the neurointerventionist’s decision to opt for stenting [32]. Both the modified first-pass effect (mTICI 2b-3; 29.8% vs. 24.8%) and recanalization rate (mTICI 2b-3; 92.9% vs. 82.2%) were numerically higher with stenting than non-stenting but these difference were not statistically significant. The puncture-to-recanalization time was longer (25 minutes) in the stenting group. Nonetheless, we observed a statistically significant shift in the distribution of mRS scores and 90-day favorable outcomes, favoring better outcomes in the stent placement group after adjusting for these confounders.
Regarding safety, one of the most concerning complications associated with stent use is the risk of hemorrhagic transformation. This risk arises from abrupt hemodynamic changes in the presence of significant ischemic injury and the early requirement for post-stroke antiplatelet agents, particularly in patients who receive IVT before the intervention. In our study, there was no evidence of heterogeneity according to thrombolysis treatment, although a higher proportion of patients in the stenting group received postoperative IV tirofiban. Importantly, the rate of sICH did not differ significantly between the two groups in adjusted analysis and was lower than rates reported in trials involving anterior circulation tandem occlusions (approximately 10% to 20%) [33-35]. These findings align with non-tandem PCAO trials, indicating a lower risk of hemorrhagic transformation in posterior circulation strokes compared to anterior circulation strokes [36-40]. This difference may be attributed to greater tolerance to ischemic injury, likely due to smaller infarct volumes, the predominance of white matter structures, and the presence of robust collateral pathways, particularly in the brainstem [41,42].
A previous study showed short-term reocclusion of the basilar artery after successful mechanical thrombectomy in 2 of the 6 patients who had been treated via the contralateral route without angioplasty or stent of the tandem VA lesion [3]. Kawano et al. [43] suggested that poorly organized thrombi in the ostial VA and the loss of downstream flow resistance following sudden mechanical recanalization of the basilar artery may be significant factors contributing to recurrent large vessel embolic occlusion.
The main advantages of extracranial VA stenting are most likely related to the augmentation of perfusion with a widely patent VA [44]. Moreover, it may decrease the risk of recurrent strokes from unstable atherosclerotic plaque embolization, subsequently decreasing the risk of early neurological deterioration and mortality. In our study, we found a significantly lower rate of early neurological deterioration and mortality at 90 days in the stenting group than in the non-stenting group. Furthermore, the cumulative 1-year mortality rate was significantly lower in the stenting group than in the non-stenting group (39.5% vs. 52.3%; P=0.01, with an aOR of 0.36, 95% CI, 0.16–0.79). The beneficial impact of acute stenting on mortality, sustained for at least 1 year, and further highlight the importance of stents in patients with acute PCTL. However, this statement cannot be verified because the BASILAR and PERSIST registries do not require followup for post-procedural VA patency verification. Additionally, the use of dual antiplatelet therapy in the post-stenting group may have played a role in secondary stroke prevention and reduction of recurrent events [45].
Our study had several significant limitations. First, there is an inherent potential for selection bias owing to its retrospective design and the absence of a control group comprising medical patients. The decision regarding the treatment of extracranial VA stenosis was left to the discretion of the operator, and the antiplatelet regimen was not standardized. Second, angiographic CT (ACT) is an effective method for assessing pre-stenting intracerebral hemorrhage. The BASILAR and PERSIST studies were initiated in China in 2024 and 2015, respectively, during which some stroke centers had access to ACT, while others did not. If a suspicious intracerebral hemorrhage was identified through ACT, these factors may have influenced the proceduralist’s decision to proceed with the stenting. Third, the status of the contralateral VA may affect the decision to proceed with stenting during the procedure and should be considered in this analysis; however, we were unable to conduct this analysis owing to the unavailability of the contralateral VA status in some cases. Fourth, long-term follow-up imaging data regarding VA patency were not available. Patency rates of the stents following the procedures were assessed in only 21 patients; among them, two experienced restenosis, and two had reocclusion. Finally, this study exclusively enrolled Han Chinese patients who exhibit a high prevalence of extracranial large-artery atherosclerosis; thus, our findings may not be generalizable to Western populations.
Conclusions
This observational registry-based study provides evidence supporting the safety and efficacy of EVT in patients with PCTL-induced AIS caused by PCTL treated within 24 hours of the estimated occlusion time. Our data also suggest that acute extracranial VA stenting during mechanical thrombectomy may enhance functional outcomes and reduce mortality rates in patients with PCTL. Similar to anterior circulation tandem occlusions [46], RCTs investigating optimal endovascular management in PCTL are warranted.
Notes
Funding statement
This project was supported by the Hainan Provincial Natural Science Foundation of China (Grant No. 823RC586) and the Research Funds of the Center for Leading Medicine and Advanced Technologies of IHM (Grant No. 2023IHM01050).
Conflicts of interest
RGN reports consulting fees for advisory roles with Anaconda, Biogen, Cerenovus, Genentech, Philips, Hybernia, Hyperfine, Imperative Care, Medtronic, Phenox, Philips, Prolong Pharmaceuticals, Stryker Neurovascular, Shanghai Wallaby, and Synchron, and stock options for advisory roles with astrocytes, Brainomix, Cerebrotech, Ceretrieve, Corindus Vascular Robotics, CrestecBio Inc., Euphrates Vascular Inc., Vesalio, Viz-AI, RapidPulse, and Perfuze. RGN is one of the Principal Investigators of the “Endovascular Therapy for Low NIHSS Ischemic Strokes (ENDOLOW)” trial. The funding for this project was provided by Cerenovus. RGN is the Principal Investigator of the “Combined Thrombectomy for Distal MediUm Vessel Occlusion StroKe (DUSK)” trial. Funding for this project was provided by Stryker Neurovascular Co.. RGN is an investor in Viz-AI, Perfuze, Cerebrotech, Reist/Q’Apel Medical, Truvic, Tulavi Therapeutics, Vastrax, Piraeus Medical, Brain- 4Care, Quantanosis AI, and Viseon. The remaining authors have no financial conflicts of interest.
Author contribution
Conceptualization: RGN, ZZ, XL. Study design: WL, MFD, TW, ZC. Methodology: MFD, ZQ, HG, HQ, WL. Data collection: ZQ, WS, WZ, QY, JH, ZH, ZC. Statistical analysis: MFD, ZQ. Writing—original draft: WL, ZQ. Writing—review & editing: RGN, ZZ, WH. Funding acquisition: WL, ZZ. Approval of final manuscript: all authors.
Acknowledgements
We are grateful for the dedication of all co-investigators of BASILAR and PERSIST to the study.