Lack of Reperfusion Rather Than Number of thrombectomy influences postoperative survival in aucte ischemic Stroke patients with large vessel occlusion

Lack of Reperfusion Rather Than Number of thrombectomy influences postoperative survival in aucte ischemic Stroke patients with large vessel occlusion | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Article Lack of Reperfusion Rather Than Number of thrombectomy influences postoperative survival in aucte ischemic Stroke patients with large vessel occlusion Canyu Zhang, Zhongju Tan, Yanfei Wu, Jiepu Wang, Peizheng Guo, and 4 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-8003829/v1 This work is licensed under a CC BY 4.0 License Status: Under Review Version 1 posted 7 You are reading this latest preprint version Abstract Background While a higher number of thrombectomy passes is widely associated with poorer clinical outcomes in acute ischemic stroke with large vessel occlusion (AIS-LVO), its relationship with long-term survival remains uninvestigated. Methods We analyzed a prospective thrombectomy database (March 2016–August 2023). All-cause mortality was assessed over a maximum follow-up of 95 months post-stroke. Multivariable Cox regression evaluated the association between the number of passes and survival time. Kaplan-Meier curves with log-rank tests compared cumulative mortality incidence. Results In patients without successful recanalization, the number of passes did not influence time to mortality. Among successfully recanalized patients, those requiring multiple passes (2, 3, or more) showed a non-significant trend toward higher mortality risk compared to single-pass recanalization. Subgroup analysis revealed a significant interaction in the gender subgroup, suggesting a differential effect of pass number on survival in female patients. Conclusion Despite requiring more attempts, successful recanalization remains beneficial for improving clinical outcomes and extending survival in AIS-LVO patients compared to failed recanalization. Health sciences/Diseases Health sciences/Medical research Health sciences/Neurology ischemic stroke large vessel occlusion mechanical thrombectomy number of passes Figures Figure 1 Figure 2 Introduction Acute ischemic stroke due to large vessel occlusion (LVO) is a leading cause of global mortality and long-term disability, with severe cases exhibiting an estimated 5-year survival rate below 50%[ 1 ]. Mechanical thrombectomy (MT) has revolutionized LVO management, demonstrating superior efficacy over intravenous thrombolysis (IVT) alone in achieving recanalization and improving functional outcomes[ 2 ]. Despite widespread MT adoption, substantial heterogeneity persists in clinical outcomes, with post-thrombectomy mortality rates ranging from 15% to 40% across different cohorts and procedural contexts[ 3 ]. Successful reperfusion remains a robust predictor of favorable clinical outcomes. Yet another critical—and understudied—prognostic factor is the number of thrombectomy passes required to achieve reperfusion. Current guidelines emphasize the first-pass effect (FPE), defined as complete recanalization (mTICI 2c/3) after a single device pass, which associates with reduced intracranial hemorrhage (ICH) risk and improved 90-day functional outcomes[ 4 , 5 ]. However, successful reperfusion often necessitates multiple passes, which may exacerbate endothelial injury, provoke distal embolization, and prolong ischemia—potentially attenuating reperfusion benefits[ 6 , 7 ]. This poses a clinical dilemma: while accumulating evidence links higher pass numbers to increased ICH risk and poorer outcomes, studies conflict on whether reperfusion success itself outweighs pass-related risks. Some report favorable outcomes only when reperfusion is achieved in ≤ 3 passes[ 8 , 9 ], whereas others suggest benefit persists irrespective of pass number[ 10 ]. Notably, a RESCUE-Japan LIMIT post hoc analysis found that recanalization requiring > 3 passes neither improved outcomes versus medical management nor reduced ICH risk[ 11 ], implying three passes may represent a viability threshold. Conversely, a matched case-control study observed improved outcomes with successful reperfusion despite multiple passes compared to failed procedures[ 12 ]. These contradictions highlight that arbitrary pass-number thresholds may inappropriately prompt premature procedural termination, potentially denying patients achievable reperfusion. Although successful reperfusion—even when requiring multiple passes—consistently confers superior prognosis over failed reperfusion[ 11 ] [ 13 ], no study has quantified the impact of pass number on long-term survival dynamics, including mortality risk and time-to-event outcomes. Whether additional passes accelerate mortality or truncate survival remains unestablished. To address this gap, we analyzed prospectively collected multicenter registry data to investigate the dose-dependent relationship between thrombectomy pass number and all-cause mortality in LVO patients, adjusting for critical confounders (collateral status, time-to-reperfusion, and post-procedural complications). Our findings aim to establish evidence-based cessation thresholds and inform risk-benefit optimization during endovascular therapy. Method Study design and populations This retrospective study analyzed consecutive AIS patients with LVO who underwent EVT between March 2016 and August 2023 at the second affiliated hospital of Zhejiang University School of university in online Fig. 1 (IR2024344). All methods were carried out in accordance with relevant guidelines and regulations. Patients were included based on the following criteria: (1) they underwent thrombectomy using second-generation stent-retriever devices or aspiration systems (e.g., Solitaire AB/FR [Covidien/ev3, Irvine, CA, USA]; Trevo Proview, Stryker, [Fremont, CA, USA]); (2) they exhibited digital subtraction angiography (DSA)-confirmed LVO, including the internal carotid artery (ICA), middle cerebral artery (MCA M1/M2), basilar artery (BA), or vertebral artery (VERT); (3) they displayed an mRS score ≤ 1 before stroke onset; (4) they had undergone EVT within 6 h of symptom onset or within 6–24 h in the presence of a large ischemic mismatch/penumbra, as determined by computed tomography (CT) perfusion[ 14 ]. Patients were excluded based on the following criteria: (1) pre-EVT intracranial hemorrhage detected on pre-procedural non-contrast computed tomography (NCCT). (2) Organ Dysfunction or Metabolic Instability like cardiac insufficiency (left ventricular ejection fraction 707 µmol/L) or uncontrolled diabetes (pre-EVT blood glucose > 22 mmol/L)[ 15 ]. (3) incomplete biomarker data: absence of pre- or post-operative lipid profile measurements due to perioperative clinical priorities or other logistical constraints. (4) loss to follow-up: unavailable 3 and 12 months mRS scores or follow-up neuroimaging post-EVT. This stringent selection protocol minimized confounding variables while ensuring cohort homogeneity and alignment with real-world clinical decision-making paradigms. Definition of mTICI The modified Thrombolysis in Cerebral Infarction (mTICI) score is a grading system used to evaluate the degree of reperfusion after endovascular treatment for acute ischemic stroke[ 14 ]. The mTICI grades are as follows: Grade 0 indicates no perfusion, with no flow through the occluded site. Grade 1 is defined as antegrade reperfusion through the initial occlusion site, but with limited filling of distal branches and slow or minimal distal reperfusion. Grade 2A covers less than half of the ischemic region of the target artery, such as one major branch of the middle cerebral artery and its corresponding region. Grade 2B covers more than half of the ischemic region, such as two major branches of the middle cerebral artery and their corresponding regions. Grade 2C indicates near-complete reperfusion, except for slow flow in a few distal cortical vessels or small distal cortical emboli, without evidence of thrombus. Grade 3 represents complete antegrade reperfusion, with all distal branches of the target artery in the ischemic region showing no visible occlusion. Grades mTICI 2b and 3 are considered successful reperfusion and are significantly associated with good clinical outcomes[ 14 ]. Statistical analysis Continuous variables are expressed as mean ± SD or median (IQR), and categorical variables are expressed as number (%). Bivariate comparisons for baseline, treatment characteristics, and outcomes between the study groups were made using the χ2 test for categorical variables and the Mann-Whitney U test for nongaussian continuous and ordinal categorical variables. Because of the relatively small number of patients with four or more retrievals, these patients were grouped into a single group. The number of passes within the vessel is defined as the number of times of stent retriever thrombectomy or aspiration thrombectomy. When the thrombectomy stent combined with suction plug is used, the number of thrombectomy is defined as 2 times. To explore the relationship between number of passes and survival state, regression analysis were adopted like univariate and multivariate COX regression. Based on that, multivariate model adjusted clinical characters, including age higher than 80 years, genernal anesthesia, NHISS higher than 14, hypertension, coronary heart disease, diabetes, and site of occlusion. The cumulative survival curve was constructed to analyze the effect of thrombectomy times on the rate of death. Subgroup analyses evaluated the heterogeneity of number of passes, including gender (Female vs. Male), age (≤ 80 vs. >80 years), mTICI (< 2B vs. ≥2B/3), anesthesia (Local vs. Genernal), circulation (anterior vs. Posterior), multistage thrombus, and distal escape. Significance was defined as two-sided P < 0.05. Analyses were performed in SPSS v22.0 (IBM Corp., USA) and R v4.3.2 (R Foundation, Austria). Results Baseline characters of patients with different number of passes Among 823 patients undergoing mechanical thrombectomy (MT), 607 met inclusion criteria. Recanalization was achieved in a single pass for 267 patients (44%), two passes for 146 (24%), three passes for 96 (16%), and over three passes for 98 (15%) in Table 1 . Higher pass numbers correlated with longer puncture-to-reperfusion (PTR) and onset-to-reperfusion (OTR) times, increased rates of general anesthesia use, and higher incidence of distal embolization, multistage thrombi, and preoperative antiplatelet therapy. Notably, occlusion patterns shifted with pass frequency: decreased incidence of middle cerebral artery (MCA) occlusions contrasted with increased frequency of anterior/posterior communicating artery (ACoA/PCoA) occlusions. Clinically, increased passes associated with poorer outcomes, manifesting as significantly higher rates of unfavorable 3-month (mRS 3–6) and 12-month functional outcomes, alongside elevated 12-month all-cause mortality post-EVT. Thrombectomy attempts were significantly associated with survive after EVT The number of thrombectomy attempts affects patients’ survival state after EVT. After correcting for confounding variables with P < 0.1 in univariate regression, the number of passes is a significant factor influencing postoperative survival time in online Table 1–2 . In Table 2 , we found that for each additional thrombectomy attempt, the postoperative survival risk of patients increases by 10% (aHR = 1.10, 95%CI 1.03 to 1.19), the risk of mortality at 3 months increased by 13% (aHR = 1.13, 95%CI 1.00 to 1.27), the risk of mortality at 12 months increased by 17% (aHR = 1.17, 95%CI 1.04 to 1.31), and the risk of symptomatic intracerebral hemorrhage (sICH) within 24 hours increased by 14% (aHR = 1.14, 95%CI 1.01 to 1.30). The cumulative survival curve in Fig. 1 indicated that the increased number of thrombectomy significantly accelerated the risk and speed of mortality of patients with AIS-LVO after EVT (P = 0.029). Cut-off value of number of thrombectomy Compared with patients who had one pass during surgery, those who had multiple thrombectomies had an increased survival risk of nearly 36% in Table 3 (aHR = 1.36, 95%CI 1.05 to 1.77), and the survival risk of patients with more than two thrombectomies was 1.32 times that of those with two or fewer thrombectomies (aHR = 1.32, 95%CI 1.01 to 1.72). When the number of passes exceeds three, the number of thrombectomy attempts being less than three is no longer a protective factor, indicating that three attempts may be the critical value for postoperative survival status. Besides, in online Table 3 , compared with thrombectomy once during the surgery, thrombectomy twice or three times had a trend of increasing the risk of death, but there was no significant difference. However, thrombectomy more than three times significantly increased the risk of death, with an increase of nearly 50% in mortality (aHR = 1.55, 95%CI 1.09 to 2.21), which suggested that we should be cautious when performing the fourth thrombectomy. Association between number of passes and survival state after EVT under different perfusion conditions Perfusion status is closely related to the prognosis and survival of patients in Table 4 . Among patients who did not achieve successful recanalization after EVT, the number of passes did not affect the speed of mortality or the risk of survival after EVT, with neither the univariate nor the multivariate Cox analysis presenting significance. In patients with successful recanalization, compared with those who achieved recanalization with a single thrombectomy, patients who underwent multiple thrombectomies (2, 3, or more passes) had an increased trend in survival risk, but there was no significant difference. This means that regardless of the number of thrombectomy attempts required to achieve the achieves reperfusion, the number of passes has no significant impact on the patient's survival time. Effect of number of passes on patients’ survival in different subgroups In the subgroups of female, local anesthesia, and posterior circulation infarction, the number of thrombectomy (≤ 3 vs > 3 passes) was strongly correlated with survival status of patients with AIS-LVO, and there was an interaction in the gender subgroup, suggesting that the number of thrombectomy may have a statistically significant cut-off value in female patients. However, in the remaining subgroups, thrombectomy greater than 3 times did not significantly affect patient survival. Discussion Our study demonstrates that successful reperfusion confers significant survival benefits in AIS-LVO patients regardless of procedural complexity. In non-recanalized patients, thrombectomy attempts (1–3 passes) showed a dose-dependent survival advantage, while > 3 passes increased mortality risk by 55% (aHR = 1.55, 95%CI 1.09–2.21), establishing three passes as an operational threshold warranting caution. Crucially, when reperfusion was achieved, no significant survival difference emerged between single-pass and multiple-pass (2, 3, or more) recanalization despite a non-significant trend toward higher mortality risk with additional passes. These findings indicate that successful reperfusion - irrespective of pass number - remains the paramount determinant for prolonging survival in AIS-LVO. Several reasons have been reported for the increased number of passes in procedure. Koge et al[ 17 ] reported that ICA tortuosity reduced likelihood of the first pass effect, which was defined as complete reperfusion with the first pass without rescue therapy, and increased the time required for reperfusion. It was also reported that fibrin-rich hard clots increased the number of passes to achieve effective reperfusion[ 18 ]. Moreover, thrombus migration also affects thrombectomy effect, as distal clot migration that embolizes the distal arterial territory and blocks the collateral flow to the potentially salvageable tissues[ 19 ]. Additional passes lead to delays in reperfusion, and time to reperfusion is critical, which also increase the risk of vascular re-occlusion[ 20 ]. One secondary analysis of RESCUE-Japan LIMIT found that the adjusted odds ratios for the primary favorable prognosis relative to medical treatment were 5.52 (2.23–14.28) after 1 pass, 6.45 (2.22–19.30) after 2 passes, 1.03 (0.15–4.48) after 3 to 7 passes, and 1.17 (0.16–5.37) if reperfusion failed, which indicated that the successful reperfusion within 2 passes was associated with better clinical outcomes[ 21 ]. A matched Case-Control Study incorporate 273 patients found that compared with matched failed reperfusion patients (n = 62), those re-perfused after 4 to 5 passes (n = 62) had a favorable shift in the overall mRS distribution (aOR = 3.992; 95%CI 1.807 to 8.512, P = 0.001) and higher rates of functional independence (31% versus 8.9%, P = 0.004, aOR = 9.860; 95%CI 2.323 to 41.845, P = 0.002) at 3 months after EVT[ 22 ]. Regarding the number of thrombectomies, most current studies focus on the relationship between the number of thrombectomies required to achieve reperfusion and patient prognosis. No studies have yet explored the impact of the number of thrombectomies under different perfusion conditions on patient survival time and the rate of death. Our study didn’t support to establish a threshold for a maximum number of passes to predict prognosis, which may lead to inappropriate early termination of procedures. Our findings suggest that successful reperfusion should be pursued in patients with AIS-LVO, even if it requires multiple attempts, which is beneficial to prolong survival time and reduce the rate of mortality. It should be emphasized, however, that all efforts should be made to achieve successful reperfusion in an efficient way, minimizing the number of attempts. In the subgroups of female, local anesthesia, and posterior circulation infarction, the number of thrombectomy was strongly correlated with survival status of patients with AIS-LVO, which indicated that we should be more careful about the timing and opportunity of thrombolysis in these patients of above subgroups. More importantly, there was an interaction in the gender subgroup, suggesting that the number of thrombectomy may have a statistically significant cut-off value in female patients. In the future, the impact of the number of thrombectomies on patient survival time and the related mechanisms in patients of different genders need to be further explored. A higher number of passes may also affect safety, as multiple thrombectomy could lead to the injury of arterial endothelial cells and the increase of vascular permeability, which may cause hemorrhage transformation (HT) or symptomatic intracranial hemorrhages (sICH), and affect the prognosis[ 23 , 24 ]. For example, one clinical trials[ 25 ] have also shown that for ischemic stroke patients undergoing EVT, thrombectomy for more than three times can improve the vascular revascularization rate, but it may not have a good clinical prognosis. This may be related to the prolongation of operative time and vascular endothelial cell injury caused by the increase of thrombectomy times mentioned above. A post hoc analysis of the Contact ASTER trial (Aspiration Versus Stent Retriever for Successful Revascularization) showed that > 3 stent-retrievers passes were associated with parenchymal hematoma compared with successful reperfusion with < 3 passes[ 26 ]. Furthermore, Endovascular treatment for ACTUAL (Acute Anterior Circulation Ischemic Stroke Registry) study showed in a subgroup analysis of 65 patients that successful reperfusion after 3 device passes was futile, which could be explained by increasing rates of sICH, higher incidence of underlying intracranial atherosclerosis (40%) and not controlling for other potential confounding variables as well[ 25 ]. However, in our cohort, with the increase of thrombectomy times, the incidence of sICH increased, but no statistical significance was found. We speculate that this may be due to the fact that the thrombectomy of the patients in our cohort included stent thrombectomy (353, 58.15%) and aspiration (254, 41.85%). What is more, when the thrombectomy stent combined with suction plug is used, the number of thrombectomy is defined as 2 times. Our study faces several constraints that merit attention. Primarily, its retrospective design precludes a definitive determination of causality. Despite the application of multivariate adjustments and subgroup analyses, the potential for residual confounding remains. Secondly, the study’s moderate sample size calls for validation through larger-scale cohort studies to reinforce our conclusions. Thirdly, the applicability of our results is primarily limited to the China context so further investigation to understand potential variations across different ethnic and geographical populations are needed. Besides, the years included in this database include the global pandemic of the COVID-19. During this period, many patients with AIS-LVO lose the ability of self-care or even death due to respiratory failure, resulting in a relatively high number of accidential death. Conclusion While an increased number of thrombectomy passes may be associated with higher postoperative mortality risk, three passes emerged as a potential threshold for clinical consideration. In patients failing reperfusion after three attempts, continued thrombectomy may still be warranted to achieve successful reperfusion with a non-significant trend toward increased sICH and mortality risk. Our findings suggest that persistent pursuit of successful reperfusion is justified in AIS-LVO patients, even when multiple attempts are required. Declarations Ethical Approval and Consent to participate This large retrospective study was approved by human Research Ethics Committee, the Second Affiliated Hospital of Zhejiang University School of Medicine (IR2024344). Without causing any potential harm to the patient, the patient's informed consent is exempt. All methods were carried out in accordance with relevant guidelines and regulations. Confirmation We confirm that manuscript complies with all instructions to authors. We confirm that this manuscript has not been published elsewhere and is not under consideration by another journal. We also confirm we use a reporting checklist (STARD checklist 2015), and will upload it as “Checklist”. Consent for publication Not applicable. Availability of data and materials Data and material are not publicly available, but can be requested. Competing interests The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. Funding This work was supported by the following grants: the Zhejiang Provincial Traditional Chinese Medicine Science and Technology Program [2025ZL604], the Taizhou Social Development Science and Technology Project [24ywa42], the Zhejiang Provincial Medical and Health Science and Technology Program [2024KY534], and the 2024 Chunan County Key Projects in Medical and Health Science and Technology Plan [2024CAYY007]. Authors’ c ontributions Conception and design: Canyu Zhang and Shandong Jiang. Acquisition of data: Jiepu Wang. and Peizheng Guo. Analysis and interpretation of data: Jiepu Wang. and Peizheng Guo. Drafting of the article: Shandong Jiang and Weibo lin. Reviewed submitted version of manuscript: all authors. Approved the final version of the manuscript on behalf of all authors: Guangtao Wang. Administrative/technical/material support: Kangqiang Tong.and Xiaodong Ling. Study supervision: Guangtao Wang Acknowledgments This work was supported by the following grants: the Zhejiang Provincial Traditional Chinese Medicine Science and Technology Program [2025ZL604], the Taizhou Social Development Science and Technology Project [24ywa42], the Zhejiang Provincial Medical and Health Science and Technology Program [2024KY534], and the 2024 Chunan County Key Projects in Medical and Health Science and Technology Plan [2024CAYY007]. References Wassélius, J., Arnberg, F., von Euler, M., Wester, P. & Ullberg, T. Endovascular thrombectomy for acute ischemic stroke. J. Intern. Med. 291 , 303–316 (2022). Goyal, M. et al. 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Available from: https://pubmed.ncbi.nlm.nih.gov/30389897/ Tables Tables 1 to 4 are available in the Supplementary Files section. Additional Declarations No competing interests reported. Supplementary Files Tables.docx Cite Share Download PDF Status: Under Review Version 1 posted Reviews received at journal 27 Feb, 2026 Reviewers agreed at journal 26 Feb, 2026 Reviewers invited by journal 26 Feb, 2026 Editor assigned by journal 17 Nov, 2025 Editor invited by journal 12 Nov, 2025 Submission checks completed at journal 10 Nov, 2025 First submitted to journal 10 Nov, 2025 You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. 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Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-8003829","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Article","associatedPublications":[],"authors":[{"id":598583991,"identity":"0d92dad6-b3b7-4521-bc76-939e9425a000","order_by":0,"name":"Canyu Zhang","email":"","orcid":"","institution":"Shangyu People's Hospital of Shaoxing University","correspondingAuthor":false,"prefix":"","firstName":"Canyu","middleName":"","lastName":"Zhang","suffix":""},{"id":598583992,"identity":"933bfc7f-9092-44b1-ba04-95acc20d5b36","order_by":1,"name":"Zhongju Tan","email":"","orcid":"","institution":"The First Affiliated Hospital of Zhejiang University School of Medicine","correspondingAuthor":false,"prefix":"","firstName":"Zhongju","middleName":"","lastName":"Tan","suffix":""},{"id":598583993,"identity":"de1fcb7a-a906-4dcd-8d7d-b77ed275f9e2","order_by":2,"name":"Yanfei Wu","email":"","orcid":"","institution":"Chun an County First People’s Hospital","correspondingAuthor":false,"prefix":"","firstName":"Yanfei","middleName":"","lastName":"Wu","suffix":""},{"id":598583994,"identity":"a384535c-c1e9-4a9a-8457-94a7282ebb4e","order_by":3,"name":"Jiepu Wang","email":"","orcid":"","institution":"The Second Affiliated Hospital of Zhejiang University School of Medicine","correspondingAuthor":false,"prefix":"","firstName":"Jiepu","middleName":"","lastName":"Wang","suffix":""},{"id":598583995,"identity":"5faa523e-0985-4db7-9eb4-3d888b8af088","order_by":4,"name":"Peizheng Guo","email":"","orcid":"","institution":"The Second Affiliated Hospital of Zhejiang University School of Medicine","correspondingAuthor":false,"prefix":"","firstName":"Peizheng","middleName":"","lastName":"Guo","suffix":""},{"id":598583996,"identity":"6fdd690e-187c-490d-9303-3f8f9263fb1f","order_by":5,"name":"Weibo lin","email":"","orcid":"","institution":"The Second Affiliated Hospital of Zhejiang University School of Medicine","correspondingAuthor":false,"prefix":"","firstName":"Weibo","middleName":"","lastName":"lin","suffix":""},{"id":598583997,"identity":"5c26298a-5da1-4326-a500-cb07b1b5ece0","order_by":6,"name":"Xiaodong Ling","email":"","orcid":"","institution":"Shangyu People's Hospital of Shaoxing University","correspondingAuthor":false,"prefix":"","firstName":"Xiaodong","middleName":"","lastName":"Ling","suffix":""},{"id":598583998,"identity":"d740a618-06fb-4f52-8555-1cf7bcb93f2b","order_by":7,"name":"Shandong Jiang","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAA6UlEQVRIie3RsUoDQRCA4TkO9poJ104K8wwL1wRS+Cq7BJJGrK8QGRDORkhrniMgKWc5sFpJmy5d0p69iGsqq3XthOzfDcwHsyxALvcPq6tHkfcPwhrAhLn8nYyfvHVrnk7GnEr03jT9iNtGy3lOICDGuPWW7GYnR4J2Zrl6k6go2IW3eLIvIgsCv7SMtyZKyoKNe1aBOF5Q0fWWCXWUqBJ0j4FsHiCQzwSCKpBRR41W34QTCCGGwzxNyMN8al6XTYc3cXJ9OPXD0N5jvfJ2P9zNrlaVj5OfN5rzZ6rU/VAlf1jO5XK5S+oLH2dKu7LrNIYAAAAASUVORK5CYII=","orcid":"","institution":"The Second Affiliated Hospital of Zhejiang University School of Medicine","correspondingAuthor":true,"prefix":"","firstName":"Shandong","middleName":"","lastName":"Jiang","suffix":""},{"id":598583999,"identity":"3534ec29-cd1e-45fb-a036-bf6372b0f838","order_by":8,"name":"Guangtao Wang","email":"","orcid":"","institution":"Municipal Hospital Affiliated to Taizhou University","correspondingAuthor":false,"prefix":"","firstName":"Guangtao","middleName":"","lastName":"Wang","suffix":""}],"badges":[],"createdAt":"2025-11-01 07:38:36","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-8003829/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-8003829/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":104169910,"identity":"51f054f3-28f5-4e69-a826-d01570ceae4a","added_by":"auto","created_at":"2026-03-08 14:41:25","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":182520,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eCumulative incidence of survival state within 95 months following up of different stratification of number of passes before operation in patients with large vascular occlusive ischemic stroke. a. 1 pass vs number of passes over 1; b. 2 passes vs number of passes over 2, c. 3 passes vs number of passes over 3; d. number of passes classification.\u003c/strong\u003e\u003c/p\u003e","description":"","filename":"1.png","url":"https://assets-eu.researchsquare.com/files/rs-8003829/v1/2ad7509674768b47458f161c.png"},{"id":104169911,"identity":"a26ad915-91c4-4fbb-aa17-5ed8fde726c1","added_by":"auto","created_at":"2026-03-08 14:41:25","extension":"png","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":292960,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eSubgroup analysis of survival states after EVT of stroke patients with AIS-LVO in different passes group (≤3 vs \u0026gt;3 passes).\u003c/strong\u003e\u003c/p\u003e","description":"","filename":"2.png","url":"https://assets-eu.researchsquare.com/files/rs-8003829/v1/9a4c866d621088592383cd2e.png"},{"id":104169913,"identity":"2c73baa0-8eb7-4493-ad3d-fe16e64cbeea","added_by":"auto","created_at":"2026-03-08 14:41:31","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":1275121,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-8003829/v1/815650c9-d37f-404e-8233-4d7e23abedc0.pdf"},{"id":104169912,"identity":"e2ee2ea6-73b4-4a03-ad4f-9adb0d765a1e","added_by":"auto","created_at":"2026-03-08 14:41:26","extension":"docx","order_by":1,"title":"","display":"","copyAsset":false,"role":"supplement","size":169550,"visible":true,"origin":"","legend":"","description":"","filename":"Tables.docx","url":"https://assets-eu.researchsquare.com/files/rs-8003829/v1/de546ab604d176da53672125.docx"}],"financialInterests":"No competing interests reported.","formattedTitle":"Lack of Reperfusion Rather Than Number of thrombectomy influences postoperative survival in aucte ischemic Stroke patients with large vessel occlusion","fulltext":[{"header":"Introduction","content":"\u003cp\u003eAcute ischemic stroke due to large vessel occlusion (LVO) is a leading cause of global mortality and long-term disability, with severe cases exhibiting an estimated 5-year survival rate below 50%[\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e]. Mechanical thrombectomy (MT) has revolutionized LVO management, demonstrating superior efficacy over intravenous thrombolysis (IVT) alone in achieving recanalization and improving functional outcomes[\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e]. Despite widespread MT adoption, substantial heterogeneity persists in clinical outcomes, with post-thrombectomy mortality rates ranging from 15% to 40% across different cohorts and procedural contexts[\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eSuccessful reperfusion remains a robust predictor of favorable clinical outcomes. Yet another critical\u0026mdash;and understudied\u0026mdash;prognostic factor is the number of thrombectomy passes required to achieve reperfusion. Current guidelines emphasize the first-pass effect (FPE), defined as complete recanalization (mTICI 2c/3) after a single device pass, which associates with reduced intracranial hemorrhage (ICH) risk and improved 90-day functional outcomes[\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e, \u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e]. However, successful reperfusion often necessitates multiple passes, which may exacerbate endothelial injury, provoke distal embolization, and prolong ischemia\u0026mdash;potentially attenuating reperfusion benefits[\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e, \u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e]. This poses a clinical dilemma: while accumulating evidence links higher pass numbers to increased ICH risk and poorer outcomes, studies conflict on whether reperfusion success itself outweighs pass-related risks. Some report favorable outcomes only when reperfusion is achieved in \u0026le;\u0026thinsp;3 passes[\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e, \u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e], whereas others suggest benefit persists irrespective of pass number[\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e]. Notably, a RESCUE-Japan LIMIT post hoc analysis found that recanalization requiring\u0026thinsp;\u0026gt;\u0026thinsp;3 passes neither improved outcomes versus medical management nor reduced ICH risk[\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e], implying three passes may represent a viability threshold. Conversely, a matched case-control study observed improved outcomes with successful reperfusion despite multiple passes compared to failed procedures[\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e]. These contradictions highlight that arbitrary pass-number thresholds may inappropriately prompt premature procedural termination, potentially denying patients achievable reperfusion.\u003c/p\u003e \u003cp\u003eAlthough successful reperfusion\u0026mdash;even when requiring multiple passes\u0026mdash;consistently confers superior prognosis over failed reperfusion[\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e] [\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e], no study has quantified the impact of pass number on long-term survival dynamics, including mortality risk and time-to-event outcomes. Whether additional passes accelerate mortality or truncate survival remains unestablished. To address this gap, we analyzed prospectively collected multicenter registry data to investigate the dose-dependent relationship between thrombectomy pass number and all-cause mortality in LVO patients, adjusting for critical confounders (collateral status, time-to-reperfusion, and post-procedural complications). Our findings aim to establish evidence-based cessation thresholds and inform risk-benefit optimization during endovascular therapy.\u003c/p\u003e"},{"header":"Method","content":"\u003cdiv id=\"Sec3\" class=\"Section2\"\u003e \u003ch2\u003eStudy design and populations\u003c/h2\u003e \u003cp\u003eThis retrospective study analyzed consecutive AIS patients with LVO who underwent EVT between March 2016 and August 2023 at the second affiliated hospital of Zhejiang University School of university in online Fig.\u0026nbsp;1 (IR2024344). All methods were carried out in accordance with relevant guidelines and regulations. Patients were included based on the following criteria: (1) they underwent thrombectomy using second-generation stent-retriever devices or aspiration systems (e.g., Solitaire AB/FR [Covidien/ev3, Irvine, CA, USA]; Trevo Proview, Stryker, [Fremont, CA, USA]); (2) they exhibited digital subtraction angiography (DSA)-confirmed LVO, including the internal carotid artery (ICA), middle cerebral artery (MCA M1/M2), basilar artery (BA), or vertebral artery (VERT); (3) they displayed an mRS score\u0026thinsp;\u0026le;\u0026thinsp;1 before stroke onset; (4) they had undergone EVT within 6 h of symptom onset or within 6\u0026ndash;24 h in the presence of a large ischemic mismatch/penumbra, as determined by computed tomography (CT) perfusion[\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e].\u003c/p\u003e \u003cp\u003ePatients were excluded based on the following criteria: (1) pre-EVT intracranial hemorrhage detected on pre-procedural non-contrast computed tomography (NCCT). (2) Organ Dysfunction or Metabolic Instability like cardiac insufficiency (left ventricular ejection fraction\u0026thinsp;\u0026lt;\u0026thinsp;40%), hepatic dysfunction (prothrombin activity [PTA]\u0026thinsp;\u0026le;\u0026thinsp;40%), renal failure (serum creatinine\u0026thinsp;\u0026gt;\u0026thinsp;707 \u0026micro;mol/L) or uncontrolled diabetes (pre-EVT blood glucose\u0026thinsp;\u0026gt;\u0026thinsp;22 mmol/L)[\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e]. (3) incomplete biomarker data: absence of pre- or post-operative lipid profile measurements due to perioperative clinical priorities or other logistical constraints. (4) loss to follow-up: unavailable 3 and 12 months mRS scores or follow-up neuroimaging post-EVT. This stringent selection protocol minimized confounding variables while ensuring cohort homogeneity and alignment with real-world clinical decision-making paradigms.\u003c/p\u003e \u003c/div\u003e\n\u003ch3\u003eDefinition of mTICI\u003c/h3\u003e\n\u003cp\u003eThe modified Thrombolysis in Cerebral Infarction (mTICI) score is a grading system used to evaluate the degree of reperfusion after endovascular treatment for acute ischemic stroke[\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e]. The mTICI grades are as follows: Grade 0 indicates no perfusion, with no flow through the occluded site. Grade 1 is defined as antegrade reperfusion through the initial occlusion site, but with limited filling of distal branches and slow or minimal distal reperfusion. Grade 2A covers less than half of the ischemic region of the target artery, such as one major branch of the middle cerebral artery and its corresponding region. Grade 2B covers more than half of the ischemic region, such as two major branches of the middle cerebral artery and their corresponding regions. Grade 2C indicates near-complete reperfusion, except for slow flow in a few distal cortical vessels or small distal cortical emboli, without evidence of thrombus. Grade 3 represents complete antegrade reperfusion, with all distal branches of the target artery in the ischemic region showing no visible occlusion. Grades mTICI 2b and 3 are considered successful reperfusion and are significantly associated with good clinical outcomes[\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e].\u003c/p\u003e \u003cdiv id=\"Sec5\" class=\"Section2\"\u003e \u003ch2\u003eStatistical analysis\u003c/h2\u003e \u003cp\u003eContinuous variables are expressed as mean\u0026thinsp;\u0026plusmn;\u0026thinsp;SD or median (IQR), and categorical variables are expressed as number (%). Bivariate comparisons for baseline, treatment characteristics, and outcomes between the study groups were made using the χ2 test for categorical variables and the Mann-Whitney U test for nongaussian continuous and ordinal categorical variables. Because of the relatively small number of patients with four or more retrievals, these patients were grouped into a single group. The number of passes within the vessel is defined as the number of times of stent retriever thrombectomy or aspiration thrombectomy. When the thrombectomy stent combined with suction plug is used, the number of thrombectomy is defined as 2 times. To explore the relationship between number of passes and survival state, regression analysis were adopted like univariate and multivariate COX regression. Based on that, multivariate model adjusted clinical characters, including age higher than 80 years, genernal anesthesia, NHISS higher than 14, hypertension, coronary heart disease, diabetes, and site of occlusion. The cumulative survival curve was constructed to analyze the effect of thrombectomy times on the rate of death. Subgroup analyses evaluated the heterogeneity of number of passes, including gender (Female vs. Male), age (\u0026le;\u0026thinsp;80 vs. \u0026gt;80 years), mTICI (\u0026lt;\u0026thinsp;2B vs. \u0026ge;2B/3), anesthesia (Local vs. Genernal), circulation (anterior vs. Posterior), multistage thrombus, and distal escape. Significance was defined as two-sided \u003cem\u003eP\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.05. Analyses were performed in SPSS v22.0 (IBM Corp., USA) and R v4.3.2 (R Foundation, Austria).\u003c/p\u003e \u003c/div\u003e"},{"header":"Results","content":"\u003cdiv id=\"Sec7\" class=\"Section2\"\u003e \u003ch2\u003eBaseline characters of patients with different number of passes\u003c/h2\u003e \u003cp\u003eAmong 823 patients undergoing mechanical thrombectomy (MT), 607 met inclusion criteria. Recanalization was achieved in a single pass for 267 patients (44%), two passes for 146 (24%), three passes for 96 (16%), and over three passes for 98 (15%) in \u003cb\u003eTable\u0026nbsp;1\u003c/b\u003e. Higher pass numbers correlated with longer puncture-to-reperfusion (PTR) and onset-to-reperfusion (OTR) times, increased rates of general anesthesia use, and higher incidence of distal embolization, multistage thrombi, and preoperative antiplatelet therapy. Notably, occlusion patterns shifted with pass frequency: decreased incidence of middle cerebral artery (MCA) occlusions contrasted with increased frequency of anterior/posterior communicating artery (ACoA/PCoA) occlusions. Clinically, increased passes associated with poorer outcomes, manifesting as significantly higher rates of unfavorable 3-month (mRS 3\u0026ndash;6) and 12-month functional outcomes, alongside elevated 12-month all-cause mortality post-EVT.\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec8\" class=\"Section2\"\u003e \u003ch2\u003eThrombectomy attempts were significantly associated with survive after EVT\u003c/h2\u003e \u003cp\u003eThe number of thrombectomy attempts affects patients\u0026rsquo; survival state after EVT. After correcting for confounding variables with P\u0026thinsp;\u0026lt;\u0026thinsp;0.1 in univariate regression, the number of passes is a significant factor influencing postoperative survival time in \u003cb\u003eonline Table\u0026nbsp;1\u0026ndash;2\u003c/b\u003e. In \u003cb\u003eTable\u0026nbsp;2\u003c/b\u003e, we found that for each additional thrombectomy attempt, the postoperative survival risk of patients increases by 10% (aHR\u0026thinsp;=\u0026thinsp;1.10, 95%CI 1.03 to 1.19), the risk of mortality at 3 months increased by 13% (aHR\u0026thinsp;=\u0026thinsp;1.13, 95%CI 1.00 to 1.27), the risk of mortality at 12 months increased by 17% (aHR\u0026thinsp;=\u0026thinsp;1.17, 95%CI 1.04 to 1.31), and the risk of symptomatic intracerebral hemorrhage (sICH) within 24 hours increased by 14% (aHR\u0026thinsp;=\u0026thinsp;1.14, 95%CI 1.01 to 1.30). The cumulative survival curve in Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003e indicated that the increased number of thrombectomy significantly accelerated the risk and speed of mortality of patients with AIS-LVO after EVT (P\u0026thinsp;=\u0026thinsp;0.029).\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003c/div\u003e\n\u003ch3\u003eCut-off value of number of thrombectomy\u003c/h3\u003e\n\u003cp\u003eCompared with patients who had one pass during surgery, those who had multiple thrombectomies had an increased survival risk of nearly 36% in \u003cb\u003eTable\u0026nbsp;3\u003c/b\u003e (aHR\u0026thinsp;=\u0026thinsp;1.36, 95%CI 1.05 to 1.77), and the survival risk of patients with more than two thrombectomies was 1.32 times that of those with two or fewer thrombectomies (aHR\u0026thinsp;=\u0026thinsp;1.32, 95%CI 1.01 to 1.72). When the number of passes exceeds three, the number of thrombectomy attempts being less than three is no longer a protective factor, indicating that three attempts may be the critical value for postoperative survival status.\u003c/p\u003e \u003cp\u003eBesides, in \u003cb\u003eonline Table\u0026nbsp;3\u003c/b\u003e, compared with thrombectomy once during the surgery, thrombectomy twice or three times had a trend of increasing the risk of death, but there was no significant difference. However, thrombectomy more than three times significantly increased the risk of death, with an increase of nearly 50% in mortality (aHR\u0026thinsp;=\u0026thinsp;1.55, 95%CI 1.09 to 2.21), which suggested that we should be cautious when performing the fourth thrombectomy.\u003c/p\u003e \u003cp\u003e \u003c/p\u003e\n\u003ch3\u003eAssociation between number of passes and survival state after EVT under different perfusion conditions\u003c/h3\u003e\n\u003cp\u003ePerfusion status is closely related to the prognosis and survival of patients in \u003cb\u003eTable\u0026nbsp;4\u003c/b\u003e. Among patients who did not achieve successful recanalization after EVT, the number of passes did not affect the speed of mortality or the risk of survival after EVT, with neither the univariate nor the multivariate Cox analysis presenting significance. In patients with successful recanalization, compared with those who achieved recanalization with a single thrombectomy, patients who underwent multiple thrombectomies (2, 3, or more passes) had an increased trend in survival risk, but there was no significant difference. This means that regardless of the number of thrombectomy attempts required to achieve the achieves reperfusion, the number of passes has no significant impact on the patient's survival time.\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cdiv id=\"Sec11\" class=\"Section2\"\u003e \u003ch2\u003eEffect of number of passes on patients\u0026rsquo; survival in different subgroups\u003c/h2\u003e \u003cp\u003eIn the subgroups of female, local anesthesia, and posterior circulation infarction, the number of thrombectomy (\u0026le;\u0026thinsp;3 vs\u0026thinsp;\u0026gt;\u0026thinsp;3 passes) was strongly correlated with survival status of patients with AIS-LVO, and there was an interaction in the gender subgroup, suggesting that the number of thrombectomy may have a statistically significant cut-off value in female patients. However, in the remaining subgroups, thrombectomy greater than 3 times did not significantly affect patient survival.\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003c/div\u003e"},{"header":"Discussion","content":"\u003cp\u003eOur study demonstrates that successful reperfusion confers significant survival benefits in AIS-LVO patients regardless of procedural complexity. In non-recanalized patients, thrombectomy attempts (1\u0026ndash;3 passes) showed a dose-dependent survival advantage, while\u0026thinsp;\u0026gt;\u0026thinsp;3 passes increased mortality risk by 55% (aHR\u0026thinsp;=\u0026thinsp;1.55, 95%CI 1.09\u0026ndash;2.21), establishing three passes as an operational threshold warranting caution. Crucially, when reperfusion was achieved, no significant survival difference emerged between single-pass and multiple-pass (2, 3, or more) recanalization despite a non-significant trend toward higher mortality risk with additional passes. These findings indicate that successful reperfusion - irrespective of pass number - remains the paramount determinant for prolonging survival in AIS-LVO.\u003c/p\u003e \u003cp\u003eSeveral reasons have been reported for the increased number of passes in procedure. Koge et al[\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e] reported that ICA tortuosity reduced likelihood of the first pass effect, which was defined as complete reperfusion with the first pass without rescue therapy, and increased the time required for reperfusion. It was also reported that fibrin-rich hard clots increased the number of passes to achieve effective reperfusion[\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e]. Moreover, thrombus migration also affects thrombectomy effect, as distal clot migration that embolizes the distal arterial territory and blocks the collateral flow to the potentially salvageable tissues[\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e]. Additional passes lead to delays in reperfusion, and time to reperfusion is critical, which also increase the risk of vascular re-occlusion[\u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e]. One secondary analysis of RESCUE-Japan LIMIT found that the adjusted odds ratios for the primary favorable prognosis relative to medical treatment were 5.52 (2.23\u0026ndash;14.28) after 1 pass, 6.45 (2.22\u0026ndash;19.30) after 2 passes, 1.03 (0.15\u0026ndash;4.48) after 3 to 7 passes, and 1.17 (0.16\u0026ndash;5.37) if reperfusion failed, which indicated that the successful reperfusion within 2 passes was associated with better clinical outcomes[\u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e]. A matched Case-Control Study incorporate 273 patients found that compared with matched failed reperfusion patients (n\u0026thinsp;=\u0026thinsp;62), those re-perfused after 4 to 5 passes (n\u0026thinsp;=\u0026thinsp;62) had a favorable shift in the overall mRS distribution (aOR\u0026thinsp;=\u0026thinsp;3.992; 95%CI 1.807 to 8.512, \u003cem\u003eP\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.001) and higher rates of functional independence (31% versus 8.9%, \u003cem\u003eP\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.004, aOR\u0026thinsp;=\u0026thinsp;9.860; 95%CI 2.323 to 41.845, \u003cem\u003eP\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.002) at 3 months after EVT[\u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e]. Regarding the number of thrombectomies, most current studies focus on the relationship between the number of thrombectomies required to achieve reperfusion and patient prognosis. No studies have yet explored the impact of the number of thrombectomies under different perfusion conditions on patient survival time and the rate of death. Our study didn\u0026rsquo;t support to establish a threshold for a maximum number of passes to predict prognosis, which may lead to inappropriate early termination of procedures. Our findings suggest that successful reperfusion should be pursued in patients with AIS-LVO, even if it requires multiple attempts, which is beneficial to prolong survival time and reduce the rate of mortality. It should be emphasized, however, that all efforts should be made to achieve successful reperfusion in an efficient way, minimizing the number of attempts. In the subgroups of female, local anesthesia, and posterior circulation infarction, the number of thrombectomy was strongly correlated with survival status of patients with AIS-LVO, which indicated that we should be more careful about the timing and opportunity of thrombolysis in these patients of above subgroups. More importantly, there was an interaction in the gender subgroup, suggesting that the number of thrombectomy may have a statistically significant cut-off value in female patients. In the future, the impact of the number of thrombectomies on patient survival time and the related mechanisms in patients of different genders need to be further explored.\u003c/p\u003e \u003cp\u003eA higher number of passes may also affect safety, as multiple thrombectomy could lead to the injury of arterial endothelial cells and the increase of vascular permeability, which may cause hemorrhage transformation (HT) or symptomatic intracranial hemorrhages (sICH), and affect the prognosis[\u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e, \u003cspan citationid=\"CR24\" class=\"CitationRef\"\u003e24\u003c/span\u003e]. For example, one clinical trials[\u003cspan citationid=\"CR25\" class=\"CitationRef\"\u003e25\u003c/span\u003e] have also shown that for ischemic stroke patients undergoing EVT, thrombectomy for more than three times can improve the vascular revascularization rate, but it may not have a good clinical prognosis. This may be related to the prolongation of operative time and vascular endothelial cell injury caused by the increase of thrombectomy times mentioned above. A post hoc analysis of the Contact ASTER trial (Aspiration Versus Stent Retriever for Successful Revascularization) showed that \u0026gt;\u0026thinsp;3 stent-retrievers passes were associated with parenchymal hematoma compared with successful reperfusion with \u0026lt;\u0026thinsp;3 passes[\u003cspan citationid=\"CR26\" class=\"CitationRef\"\u003e26\u003c/span\u003e]. Furthermore, Endovascular treatment for ACTUAL (Acute Anterior Circulation Ischemic Stroke Registry) study showed in a subgroup analysis of 65 patients that successful reperfusion after 3 device passes was futile, which could be explained by increasing rates of sICH, higher incidence of underlying intracranial atherosclerosis (40%) and not controlling for other potential confounding variables as well[\u003cspan citationid=\"CR25\" class=\"CitationRef\"\u003e25\u003c/span\u003e]. However, in our cohort, with the increase of thrombectomy times, the incidence of sICH increased, but no statistical significance was found. We speculate that this may be due to the fact that the thrombectomy of the patients in our cohort included stent thrombectomy (353, 58.15%) and aspiration (254, 41.85%). What is more, when the thrombectomy stent combined with suction plug is used, the number of thrombectomy is defined as 2 times.\u003c/p\u003e \u003cp\u003eOur study faces several constraints that merit attention. Primarily, its retrospective design precludes a definitive determination of causality. Despite the application of multivariate adjustments and subgroup analyses, the potential for residual confounding remains. Secondly, the study\u0026rsquo;s moderate sample size calls for validation through larger-scale cohort studies to reinforce our conclusions. Thirdly, the applicability of our results is primarily limited to the China context so further investigation to understand potential variations across different ethnic and geographical populations are needed. Besides, the years included in this database include the global pandemic of the COVID-19. During this period, many patients with AIS-LVO lose the ability of self-care or even death due to respiratory failure, resulting in a relatively high number of accidential death.\u003c/p\u003e"},{"header":"Conclusion","content":"\u003cp\u003eWhile an increased number of thrombectomy passes may be associated with higher postoperative mortality risk, three passes emerged as a potential threshold for clinical consideration. In patients failing reperfusion after three attempts, continued thrombectomy may still be warranted to achieve successful reperfusion with a non-significant trend toward increased sICH and mortality risk. Our findings suggest that persistent pursuit of successful reperfusion is justified in AIS-LVO patients, even when multiple attempts are required.\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eEthical Approval and Consent to participate\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThis large retrospective study was approved by human Research Ethics Committee, the Second Affiliated Hospital of\u0026nbsp;Zhejiang University School of Medicine\u0026nbsp;(IR2024344). Without causing any potential harm to the patient, the patient\u0026apos;s informed consent is exempt. All methods were carried out in accordance with relevant guidelines and regulations.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConfirmation\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eWe confirm that manuscript complies with all instructions to authors. We confirm that this manuscript has not been published elsewhere and is not under consideration by another journal. We also confirm we use a reporting checklist (STARD checklist 2015), and will upload it as \u0026ldquo;Checklist\u0026rdquo;.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConsent for publication\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNot applicable.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAvailability of data and materials\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eData and material are not publicly available, but can be requested.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCompeting interests\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFunding\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThis work was supported by the following grants: the Zhejiang Provincial Traditional Chinese Medicine Science and Technology Program [2025ZL604], the Taizhou Social Development Science and Technology Project [24ywa42], the Zhejiang Provincial Medical and Health Science and Technology Program [2024KY534], and the 2024 Chunan County Key Projects in Medical and Health Science and Technology Plan [2024CAYY007].\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAuthors\u0026rsquo;\u003c/strong\u003e\u003cstrong\u003e\u0026nbsp;c\u003c/strong\u003e\u003cstrong\u003eontributions\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eConception and design: Canyu Zhang and Shandong Jiang.\u003c/p\u003e\n\u003cp\u003eAcquisition of data: Jiepu Wang. and Peizheng Guo.\u003c/p\u003e\n\u003cp\u003eAnalysis and interpretation of data: Jiepu Wang. and Peizheng Guo.\u003c/p\u003e\n\u003cp\u003eDrafting of the article: Shandong Jiang and Weibo lin.\u003c/p\u003e\n\u003cp\u003eReviewed submitted version of manuscript: all authors.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eApproved the final version of the manuscript on behalf of all authors: Guangtao Wang.\u003c/p\u003e\n\u003cp\u003eAdministrative/technical/material support: Kangqiang Tong.and Xiaodong Ling.\u003c/p\u003e\n\u003cp\u003eStudy supervision: Guangtao Wang\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAcknowledgments\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThis work was supported by the following grants: the Zhejiang Provincial Traditional Chinese Medicine Science and Technology Program [2025ZL604], the Taizhou Social Development Science and Technology Project [24ywa42], the Zhejiang Provincial Medical and Health Science and Technology Program [2024KY534], and the 2024 Chunan County Key Projects in Medical and Health Science and Technology Plan [2024CAYY007].\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\u003cli\u003e\u003cspan\u003eWass\u0026eacute;lius, J., Arnberg, F., von Euler, M., Wester, P. \u0026amp; Ullberg, T. 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J. Neuroradiol.\u003c/em\u003e \u003cb\u003e38\u003c/b\u003e, 1368\u0026ndash;1371 (2017).\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eFlottmann, F. et al. Good Clinical Outcome Decreases With Number of Retrieval Attempts in Stroke Thrombectomy: Beyond the First-Pass Effect. \u003cem\u003eStroke\u003c/em\u003e \u003cb\u003e52\u003c/b\u003e, 482\u0026ndash;490 (2021).\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eRecanalization Rate per Retrieval Attempt in Mechanical Thrombectomy for Acute. Ischemic Stroke - PubMed [Internet]. [cited 2025 Feb 24]. Available from: \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://pubmed.ncbi.nlm.nih.gov/30355115/\u003c/span\u003e\u003cspan address=\"https://pubmed.ncbi.nlm.nih.gov/30355115/\" targettype=\"URL\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eCorrection to. 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Neurointerv Surg.\u003c/em\u003e \u003cb\u003e14\u003c/b\u003e, 1077\u0026ndash;1083 (2022).\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eK, J. K. \u0026amp; T, T. Y, M S, Y K, T O, et al. Internal Carotid Artery Tortuosity: Impact on Mechanical Thrombectomy. Stroke [Internet]. 2022 [cited 2025 Feb 24];53. Available from: \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://pubmed.ncbi.nlm.nih.gov/35400203/\u003c/span\u003e\u003cspan address=\"https://pubmed.ncbi.nlm.nih.gov/35400203/\" targettype=\"URL\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eI, Y., Hv, I. K., Rh, V. \u0026amp; Fa, K. A. G. V, et al. The impact of thromboemboli histology on the performance of a mechanical thrombectomy device. AJNR American journal of neuroradiology [Internet]. 2012 [cited 2025 Feb 24];33. Available from: \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://pubmed.ncbi.nlm.nih.gov/22207297/\u003c/span\u003e\u003cspan address=\"https://pubmed.ncbi.nlm.nih.gov/22207297/\" targettype=\"URL\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003ePilato, F. et al. Clot evaluation and distal embolization risk during mechanical thrombectomy in anterior circulation stroke. \u003cem\u003eJ. Neurol. Sci.\u003c/em\u003e \u003cb\u003e432\u003c/b\u003e, 120087 (2022).\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003ePadma, S. \u0026amp; Majaz, M. Intra-arterial versus intra-venous thrombolysis within and after the first 3 hours of stroke onset. \u003cem\u003eArch. Med. Sci.\u003c/em\u003e \u003cb\u003e6\u003c/b\u003e, 303\u0026ndash;315 (2010).\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eNamitome, S. et al. Number of Passes of Endovascular Therapy for Stroke With a Large Ischemic Core: Secondary Analysis of RESCUE-Japan LIMIT. \u003cem\u003eStroke\u003c/em\u003e \u003cb\u003e54\u003c/b\u003e, 1985\u0026ndash;1992 (2023).\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eMohammaden, M. H. et al. Lack of Reperfusion Rather Than Number of Passes Defines Futility in Stroke Thrombectomy: A Matched Case-Control Study. \u003cem\u003eStroke\u003c/em\u003e \u003cb\u003e52\u003c/b\u003e, 2757\u0026ndash;2763 (2021).\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eBroderick, J. P. et al. Endovascular therapy after intravenous t-PA versus t-PA alone for stroke. \u003cem\u003eN Engl. J. Med.\u003c/em\u003e \u003cb\u003e368\u003c/b\u003e, 893\u0026ndash;903 (2013).\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eArai, D., Ishii, A., Chihara, H., Ikeda, H. \u0026amp; Miyamoto, S. Histological examination of vascular damage caused by stent retriever thrombectomy devices. \u003cem\u003eJ. Neurointerv Surg.\u003c/em\u003e \u003cb\u003e8\u003c/b\u003e, 992\u0026ndash;995 (2016).\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eImpact of Retriever Passes on Efficacy and Safety Outcomes of Acute. Ischemic Stroke Treated with Mechanical Thrombectomy - PubMed [Internet]. [cited 2025 Feb 24]. Available from: \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://pubmed.ncbi.nlm.nih.gov/29998416/\u003c/span\u003e\u003cspan address=\"https://pubmed.ncbi.nlm.nih.gov/29998416/\" targettype=\"URL\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eR B, S S, J L, M M, R F, R B, et al. More than three passes of stent retriever is an independent predictor of parenchymal hematoma in acute ischemic stroke. Journal of neurointerventional surgery [Internet]. [cited 2025 Feb 24];11. (2019). Available from: \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://pubmed.ncbi.nlm.nih.gov/30389897/\u003c/span\u003e\u003cspan address=\"https://pubmed.ncbi.nlm.nih.gov/30389897/\" targettype=\"URL\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e\u003c/ol\u003e"},{"header":"Tables","content":"\u003cp\u003eTables 1 to 4 are available in the Supplementary Files section.\u003c/p\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":false,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"scientific-reports","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"scirep","sideBox":"Learn more about [Scientific Reports](http://www.nature.com/srep/)","snPcode":"","submissionUrl":"","title":"Scientific Reports","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"stoa","reportingPortfolio":"Scientific Reports","inReviewEnabled":true,"inReviewRevisionsEnabled":true},"keywords":"ischemic stroke, large vessel occlusion, mechanical thrombectomy, number of passes","lastPublishedDoi":"10.21203/rs.3.rs-8003829/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-8003829/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003ch2\u003eBackground\u003c/h2\u003e \u003cp\u003eWhile a higher number of thrombectomy passes is widely associated with poorer clinical outcomes in acute ischemic stroke with large vessel occlusion (AIS-LVO), its relationship with long-term survival remains uninvestigated.\u003c/p\u003e\u003ch2\u003eMethods\u003c/h2\u003e \u003cp\u003eWe analyzed a prospective thrombectomy database (March 2016\u0026ndash;August 2023). All-cause mortality was assessed over a maximum follow-up of 95 months post-stroke. Multivariable Cox regression evaluated the association between the number of passes and survival time. Kaplan-Meier curves with log-rank tests compared cumulative mortality incidence.\u003c/p\u003e\u003ch2\u003eResults\u003c/h2\u003e \u003cp\u003eIn patients without successful recanalization, the number of passes did not influence time to mortality. Among successfully recanalized patients, those requiring multiple passes (2, 3, or more) showed a non-significant trend toward higher mortality risk compared to single-pass recanalization. Subgroup analysis revealed a significant interaction in the gender subgroup, suggesting a differential effect of pass number on survival in female patients.\u003c/p\u003e\u003ch2\u003eConclusion\u003c/h2\u003e \u003cp\u003eDespite requiring more attempts, successful recanalization remains beneficial for improving clinical outcomes and extending survival in AIS-LVO patients compared to failed recanalization.\u003c/p\u003e","manuscriptTitle":"Lack of Reperfusion Rather Than Number of thrombectomy influences postoperative survival in aucte ischemic Stroke patients with large vessel occlusion","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2026-03-08 14:41:20","doi":"10.21203/rs.3.rs-8003829/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"editorInvitedReview","content":"","date":"2026-02-28T03:00:57+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"172386699454544191006077287131464547324","date":"2026-02-26T06:09:57+00:00","index":"hide","fulltext":""},{"type":"reviewersInvited","content":"","date":"2026-02-26T05:57:32+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2025-11-17T16:25:50+00:00","index":"","fulltext":""},{"type":"editorInvited","content":"","date":"2025-11-12T08:57:53+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2025-11-10T05:42:02+00:00","index":"","fulltext":""},{"type":"submitted","content":"Scientific Reports","date":"2025-11-10T05:38:57+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"scientific-reports","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"scirep","sideBox":"Learn more about [Scientific Reports](http://www.nature.com/srep/)","snPcode":"","submissionUrl":"","title":"Scientific Reports","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"stoa","reportingPortfolio":"Scientific Reports","inReviewEnabled":true,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"39ddadde-5676-4f40-b62f-ab6653ff030c","owner":[],"postedDate":"March 8th, 2026","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"under-review","subjectAreas":[{"id":63702180,"name":"Health sciences/Diseases"},{"id":63702181,"name":"Health sciences/Medical research"},{"id":63702182,"name":"Health sciences/Neurology"}],"tags":[],"updatedAt":"2026-03-08T14:41:20+00:00","versionOfRecord":[],"versionCreatedAt":"2026-03-08 14:41:20","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-8003829","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-8003829","identity":"rs-8003829","version":["v1"]},"buildId":"XKTyCvWXoU3ODBz1xrDgd","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}