Subgroup Analysis Meta-analysis with First-line Technique Ischemic Stroke: A Systematic Review and Endovascular Thrombectomy in Acute without Balloon Guide Catheters during Clinical and Procedural Outcomes with or

BACKGROUND: Balloon guide catheters are increasingly used to improve clot retrieval by temporarily stopping proximal blood ﬂ ow during endovascular thrombectomy. PURPOSE: Our aim was to provide a summary of the literature comparing the procedural and clinical outcomes of endovascular thrombectomy with or without balloon guide catheters, depending on the ﬁ rst-line technique used. DATA SOURCES: We used PubMed/MEDLINE, EMBASE, and the Cochrane Database of Systematic Reviews. STUDY SELECTION: We chose studies that compared using balloon guide catheters with not using them. DATA ANALYSIS: Random effects meta-analysis was performed to compare the procedural outcomes measured as the ﬁ rst-pass effect, successful reperfusion, number of passes, procedural duration, arterial puncture to reperfusion time, distal emboli, and clinical outcomes. DATA SYNTHESIS: Overall, a meta-analysis of 16 studies (5507 patients, 50.8% treated with balloon guide catheters and 49.2% without them) shows that the use of balloon guide catheters increases the odds of achieving a ﬁ rst-pass effect (OR ¼ 1.92; 95% CI, 1.34 – 2.76; P , .001), successful reperfusion (OR ¼ 1.85; 95% CI, 1.42 – 2.40; P , .001), and good functional outcome (OR ¼ 1.48; 95% CI, 1.27 – 1.73; P , .001). Balloon guide catheters reduce the number of passes (mean difference ¼ (cid:2) 0.35; 95% CI, (cid:2) 0.65 to (cid:2) 0.04; P ¼ .02), procedural time (mean difference ¼ (cid:2) 19.73; 95% CI, (cid:2) 34.63 to (cid:2) 4.83; P ¼ .009), incidence of distal or new territory emboli (OR ¼ 0.5; 95% CI, 0.26 – 0.98; P ¼ .04), and mortality (OR ¼ 0.72; 95% CI, 0.62 – 0.85; P , .001). Similar bene ﬁ ts of balloon guide catheters are observed when the ﬁ rst-line technique was a stent retriever or contact aspiration, but not for a combined approach. LIMITATIONS: The analysis was based on nonrandomized trials with a moderate risk of bias. CONCLUSIONS: Current literature suggests improved clinical and procedural outcomes associated with the use of balloon guide catheters during endovascular thrombectomy, especially when using the ﬁ rst-line stent retriever.

Combined techniques of stent retriever and contact aspiration have also been shown to result in high rates of successful reperfusion and good functional outcomes and are now increasingly used. 13,14uring endovascular thrombectomy, using a balloon guide catheter has been associated with higher recanalization rates and better functional outcomes in early clinical studies. 15,16Balloon guide catheters offer transient proximal flow arrest and decrease the forward pressure impacting the clot, which has been shown to prevent distal thrombus migration or embolization to new vascular territories during retrieval. 17,18Despite level 2A evidence suggesting benefits of stent retrievers in conjunction with proximal balloon guide catheters, 2 there is continued debate over their use in everyday clinical practice, especially when used in conjunction with contact aspiration.
Two previous meta-analyses suggested that the use of balloon guide catheters during endovascular thrombectomy is associated with improved clinical and angiographic outcomes. 19,20However, a few larger registries have since been published in addition to many endovascular thrombectomy procedural modifications.Thus, we conducted this updated systematic review to investigate the effects of balloon guide catheters on the clinical and procedural outcomes following endovascular thrombectomy and considering the first-line endovascular thrombectomy technique: stent retriever, contact aspiration, or a combination (stent retriever 1 contact aspiration).

Search Strategy, Study Selection, and Eligibility Criteria
The study was performed per the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. 21e systematically searched electronic data bases up to December 2020, including PubMed/MEDLINE, EMBASE, and the Cochrane Database of Systematic Reviews.The following keywords were used in combination or individually using the Boolean operators "OR" and "AND": "thrombectomy," "endovascular procedures," "stroke," "retrievable stent," "stent retriever," "stentriever," "aspiration," "suction," and "balloon guided catheter."The articles were selected in 2 stages.First, the titles and abstracts were screened for relevant studies.Second, the full texts were downloaded and assessed for eligibility.The reference lists of included publications were then hand-searched for additional relevant studies.This process was performed by 4 assessors independently (A.P., G.J., A.S., P.S.D.).Any differences were resolved by consensus.
Studies evaluating $1 procedural and clinical outcome of endovascular thrombectomy were included.Randomized and nonrandomized controlled (retrospective and prospective) trials, observational studies, or post hoc analyses of observational data in trials were included when a control group was reported.Exclusion criteria included studies published before 2009, review articles and meta-analyses, guidelines, technical notes, studies on animals, and studies in languages other than English.
In the case of an overlapping patient population, only the series with the largest number of patients or the most detailed data were included.

Data Extraction
The variables were, if available, the following: use of balloon guide catheters, the first-line endovascular thrombectomy technique used, study type (retrospective, prospective), study period, anatomic region (anterior/posterior circulation), sample size, mean age, number of women, presence of comorbidities (atrial fibrillation, hypertension, diabetes, coronary artery disease, dyslipidemia, smoking), tandem occlusion, clot location, baseline NIHSS score, IV-tPA, use of general anesthesia, use of a distal-access catheter, use of intra-arterial thrombolysis, onset to arterial puncture time, arterial puncture to reperfusion time, total procedural time (the time from the sheath insertion until the sheath is out), number of passes, successful reperfusion rate (defined as extended TICI [eTICI] 2b 22 or higher), first-pass effect defined as eTICI 2b or higher 16,18,[23][24][25] or eTICI 2c or higher [25][26][27] or eTICI 3 [28][29][30] or complete reperfusion 18,28 after the first pass, good functional outcome defined as functional independence described as mRS #2 at 90 days, symptomatic intracranial hemorrhage (sICH) defined as any ICH with an increase of the NIHSS score of $4 within 24 hours or death, and mortality at 90 days.

Outcome Measures
Study characteristics and extracted variables were summarized using standard descriptive statistics.Continuous variables were expressed as means (SD), and categoric variables were expressed as frequencies or percentages.The primary outcomes were procedural (the firstpass effect, successful recanalization, procedural time, arterial puncture to reperfusion time, number of passes, distal embolization, or embolization in the new territory) and clinical (good functional outcome [mRS #2] at 90 days, sICH, mortality at 90 days).

Statistical Analysis
Binary outcomes are reported as ORs with 95% confidence intervals.Continuous outcomes are analyzed as mean difference with a 95% CI.Tests of heterogeneity were conducted with the Q-statistic distributed as a x 2 variate (assumption of homogeneity of effect sizes).The extent of between-study heterogeneity was assessed with the I 2 statistic. 31,32A random effects model was used.The ROBINS-I 33,34 tool was used to evaluate and visualize the individual risk of bias of each study.P values were 2-tailed with values , .05 considered statistically significant.All analyses were conducted in Statistica 13.1 (StatSoft Poland), online calculators, and Review Manager 5.4.1 software (https://www.advanceduninstaller.com/Review-Manager-5_4_1-509a434684edfe58c850c849ab795eca-application.htm). 35

Ethics
This study is a systematic review and meta-analysis, and no human-participant procedure was involved.Informed consent and ethics approval were not essential for this study.

Risk of Bias
The risk of bias was moderate in 13 studies and low in 3 studies (Online Supplemental Data).

DISCUSSION
Our systematic review and meta-analysis of 5507 patients suggests that the use of a balloon guide catheter increases the odds of achieving the first-pass effect and successful reperfusion and reduces the procedural time, the number of passes, and distal embolization or emboli in a new vascular territory.Furthermore, the use of a balloon guide catheter increases the odds of achieving good functional outcome and reduces the risk of death, without influencing the risk of sICH.This updated review, which includes recent large patient cohort registries, is among the largest metaanalysis on this topic to date. 18,25,26,37,39Our findings validate the results of previous meta-analyses 20,44 and expand to report the procedural and clinical outcomes according to the first-line endovascular thrombectomy technique.
A longer procedural time is associated with a lower likelihood of a good functional outcome and a higher probability of sICH.Some observed a transition point at 30 minutes when the cumulative rate of good functional outcome drops by 40%. 45Similar to the results of endovascular thrombectomy workflow analysis studies, 46 our findings show that the use of a balloon guide catheter is associated with a shorter total procedural time.This likely corresponds to fewer passes required and an increased first-pass effect.In accordance with the Trevo Acute Ischemic Stroke (TRACK) Multicenter Registry analysis, high-volume centers use balloon guide catheters most often. 47ur findings confirmed a reduction in distal clot embolizations, including those to new vascular territories.Previous studies have also demonstrated that the balloon guide catheter reduces clot fragmentation and distal embolic shower and provides more effective revascularization, 48 but this was not reported in previous metaanalyses. 19,20In vitro studies have also reported that the use of proximal flow control by a balloon guide catheter significantly reduced the formation of large distal emboli with a diameter of .1 mm. 49here remains ambiguity over the best first-line endovascular thrombectomy technique (stent retriever, contact aspiration, or combined) when used in conjunction with a balloon guide catheter.For instance, Baek et al 18 analyzed 955 participants and reported that the positive influence of a balloon guide catheter on procedural and clinical outcomes is independent of the firstline treatment technique, whereas Goldhoorn et al 37 reported no difference in the clinical outcome in each stent-retriever and contact-aspiration group, with or without a balloon guide catheter.Bourcier et al 26 also observed no difference between balloon guide catheters and conventional guide catheters when the stent-retriever technique was combined with contact aspiration.The recent Contact Aspiration vs Stent Retriever for Successful Revascularization (ASTER2) trial compared the use of the combined approach versus stent retriever only; both used balloon guide catheters.The authors demonstrated no significant differences in the procedural and functional outcomes, though there was a tendency toward the combined technique. 50,51Our subgroup analysis suggests that the most significant benefit of a balloon guide catheter is in conjunction with the first-line stentretriever approach.Balloon guide catheters also improve successful reperfusion rates and good clinical outcomes when used during contact aspiration.However, there is currently insufficient evidence regarding their use during a combined-approach technique.
Balloon guide catheters have limitations related to their construction: 1) a larger outer diameter requiring larger introductory sheaths, 2) larger aspiration catheters not compatible with most balloon guide catheters, and 3) a relatively more rigid construct rendering endovascular navigation with balloon guide catheter more challenging.However, new balloon guide catheters with larger internal diameters of up to 0.087 inches are able to accommodate large-bore aspiration catheters and can still be used through an 8F sheath. 52,53Concerns have also been raised about potential groin complications, especially among patients on anticoagulants or IV-tPA. 17However, a recent study of 472 patients reported only a 0.4%-0.8%risk of sheath-related groin complications for balloon guide catheters. 54

Limitations and Further Directions
None of the included studies were randomized, and most of them were weighted with a moderate risk of bias.Furthermore, the included studies had a high heterogeneity level except for the overall clinical outcomes (I 2 was 30% for good clinical outcome, 28% for sICH, and 0% for mortality).There were differences in the baseline characteristics of the population.Atrial fibrillation and ICA occlusions were more frequently identified in the balloon guide catheter group.Most interesting, data from the ASTER2 trial suggest better efficacy in a subset of patients with distal ICA occlusions when balloon guide catheters with the combined technique were used. 50,51eriprocedurally, distal access catheter use and intra-arterial thrombolysis administration were less frequently observed in the balloon guide catheter group (Table 2.) While we extracted the baseline characteristics of the clot location, the studies did not report the outcome measures in these subgroups, precluding direct comparison.
A small number of posterior circulation strokes (n ¼ 35) from a single study were included in our meta-analysis. 15However, it was not possible to extract the outcome measures for this cohort of patients or exclude this cohort from the analysis because the relevant outcomes were not separately reported.
Additional factors that may influence the outcome of endovascular thrombectomy with balloon guide catheter use are its position and the adequacy of the balloon inflation.The latter could not be reliably assessed in the included studies.Jeong et al 55 compared proximal and distal positions of balloon guide catheters in the carotid artery among 102 patients.They reported that a shorter procedural time and higher recanalization rates were associated with a more distal balloon guide catheter position.Another factor is the size and positioning of the stent retriever.The Systematic Evaluation of Patients Treated with Neurothrombectomy Devices for Acute Ischemic Stroke (STRATIS) registry showed that the size of the stent retriever may have a positive influence on successful recanalization rates, regardless of the use of a balloon guide catheter. 56However, information concerning the size of the stent retriever used was not provided by all studies.
A uniform assessment of emboli in new territories was lacking in most studies, mainly due to the lack of subsequent MR imaging after the procedure.For example, Schönfeld et al 27 studied 37 patients with successful reperfusion (TICI 2b or higher) following endovascular thrombectomy (with or without a balloon guide catheter) who had subsequent MR imaging with a DWI sequence within 24 hours.They reported that the use of a balloon guide catheter led to a significant reduction in the number and volume of peripheral emboli, with a median number/volume of peripheral emboli of 4.5/287 versus 12/938 mL. 27However, the assessment of embolic showers in new territories is generally difficult because its definition often varies among studies.
Further randomized trials 57 are needed to evaluate our findings while taking into account other factors such as clot localization and composition and the first-line endovascular thrombectomy technique.While a large proportion of the included studies investigated and highlighted the benefits of balloon guide catheters with stent retrievers, the use of stent retrievers only in modern day endovascular thrombectomy is diminishing.Instead, the combined approach or contact aspiration-only first-line techniques are increasingly adopted in many centers.However, there is a lack of data on the efficacy of balloon guide catheter use in both groups, which are under-represented in our study.

CONCLUSIONS
Current literature and our meta-analysis confirm the benefits of balloon guide catheters in achieving shorter total procedural times.The balloon guide catheter improves the successful reperfusion rate and good clinical outcomes when used during firstline contact aspiration or stent retrieval but not with a combined approach.

FIGURE.
FIGURE.Clinical outcomes.This figure is a summary of random effects forest plots showing studies divided into the 3 groups depending on the first-line endovascular thrombectomy technique.A, Good functional outcome at 90 days.B, sICH.C, Mortality at 90 days.SR indicates stent retriever versus combined versus contact aspiration (CA).

Table 1 :
Baseline characteristics of the included studies Note:-BGC indicates balloon guide catheter.

Table 2 :
Summary of balloon guide catheter effects on procedural and clinical outcomes Note:-NA indicates not available; SR, stent retriever; CA, contact aspiration; :, increase; ;, decrease; -, no difference.