Puncture-to-Reperfusion Time Threshold Guides Procedural Termination in Thrombectomy: Analysis from the ANGEL-ACT Registry

Puncture-to-Reperfusion Time Threshold Guides Procedural Termination in Thrombectomy: Analysis from the ANGEL-ACT Registry | 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 Puncture-to-Reperfusion Time Threshold Guides Procedural Termination in Thrombectomy: Analysis from the ANGEL-ACT Registry Zequan Yu, Fangguang Chen, Hao Feng, Xiaobing Li, Wei Liu, Zhongrong Miao This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-6332896/v1 This work is licensed under a CC BY 4.0 License Status: Posted Version 1 posted You are reading this latest preprint version Abstract Purpose The role of puncture-to-reperfusion time (PRT) remains under investigation. Our study aimed to explore whether it could serve as an indicator for procedural termination. Methods Patients who underwent endovascular therapy within 6 hours of onset due to anterior large-vessel occlusion were selected from ANGEL-ACT. Restricted cubic splines (RCS) with 3 knots defined PRT thresholds. Outcomes were compared successful reperfusion with prolonged PRT (PRT > 51 min) and partial reperfusion groups. Potential subgroups who might benefit from prolonged PRT were compared. Primary outcome was 90-day mRS, safety outcomes were mortality at 90days, any intracranial hemorrhage and symptomatic intracranial hemorrhage. Results 51 minutes was determined as PRT cutoff in our study. Those achieved successful reperfusion with prolonged PRT had higher mRS 0–3 rate compared with those achieved partial reperfusion (aOR 2.86 [95% CI 1.21–6.76], P = 0.02); No significant differences were found in other outcomes. Subgroup analysis indicated similar result in patients aged < 65 years, while no significant difference in primary outcome was observed in intravenous thrombolysis subgroup and ASPECTS ≥ 8 subgroup. Conclusion Our findings suggest that prolonged PRT improves outcomes, particularly in patients < 65 years, but not in patients received intravenous thrombolysis or ASPECTS ≥ 8. Individualized termination protocols are needed, pending further validation. Biological sciences/Neuroscience/Diseases of the nervous system/Stroke Health sciences/Neurology/Neurological disorders/Cerebrovascular disorders/Stroke thrombectomy puncture-to-reperfusion time mRS RCS Figures Figure 1 Figure 2 Introduction Endovascular treatment (EVT) has been established as the first-line therapy for acute ischemic stroke caused by large vessel occlusion (LVO) 1 – 7 . However, 41–43% of patients fail to achieve favorable functional outcomes (modified Rankin Scale [mRS] 0–2) despite successful recanalization, a clinical conundrum termed futile recanalization 8 . While multiple determinants contribute to this phenomenon, including collateral status, infarct core volume, and reperfusion injury, procedural duration, quantified by puncture-to-reperfusion time (PRT), has emerged as a critical modifiable predictor of clinical outcomes 9 – 11 . Prolonged PRT not only correlates with escalating rate of complication but also diminishes the likelihood of meaningful neurological improvement 12 . The HERMES collaboration consensus advocates PRT ≤ 60 minutes an optimal threshold 13 . However, this consensus faces profound implementation challenges in clinical practice. In technically challenging cases, characterized by tortuous access to the occlusion site, refractory thrombi, or tandem occlusions, adjunctive techniques and iterative thrombectomy attempts are needed, inevitably prolonging PRT beyond recommended threshold. This operational reality creates a therapeutic dilemma: clinicians must balance the diminishing therapeutic efficacy of eventual successful recanalization against the risks of prematurely terminating recanalization. There are many studies linking excessive thrombectomy attempts to attenuated clinical benefit 14 – 16 , however, such standard fails to apply when adjunctive techniques are needed, which undermined the necessity for operator flexibility. Current guidelines provide limited consensus on termination criteria for persistently unsuccessful thrombectomy attempts. Crucially, the prognostic value of PRT threshold as a potential termination indicator remains underexplored. This study hypothesizes that the therapeutic time window for PRT exhibits population-specific boundaries, beyond which continued thrombectomy attempts offset the potential benefits of successful recanalization. We aim to (1) identify the PRT threshold predictive of futile recanalization, and (2) delineate patient subgroups that may or may not benefit from extended procedural duration. METHODS Study population and study design We conducted a retrospective analysis of the Endovascular Treatment Key Technique and Emergency Workflow Improvement of Acute Ischemic Stroke (ANGEL-ACT) Registry, a prospective multicenter registry (ClinicalTrial.gov ID: NCT03370939), which consecutively enrolled 1793 acute ischemic stroke patients receiving endovascular reperfusion therapy across 111 Chinese centers (November 2017 to March 2019). Detailed inclusion and exclusion criteria have been previously documented 17 . Written informed consent was obtained from all patients or their legally authorized representatives. A group of patients was identified from this registry. Inclusion criteria are ischemic stroke due to anterior LVO confirmed by CTA/MRA/DSA, onset-puncture time ≤ 6 hours, baseline ASPECTS ≥ 6 on non-contrast CT. Successful reperfusion was assessed using the modified thrombolysis in cerebral infarction (mTICI) scale, mTICI 2b-3 indicated successful reperfusion, while an mTICI score of 0-2a indicated partial reperfusion. Restricted cubic spline (RCS) with 3 knots (10th, 50th, 90th percentiles) were implemented to model nonlinear relationships between PRT and favorable functional outcome and to determine the cutoff value of PRT, the optimal PRT threshold was determined by maximizing the adjusted odds ratio (aOR) in multivariable logistic regression. Patients achieving successful reperfusion beyond the PRT threshold were compared to those with partial reperfusion irrespective of procedural duration. Subgroup analyses were also performed based on the following factors: (1) Age (< 65 vs ≥ 65 years), (2) intravenous thrombolysis (yes/no), (3) baseline National Institutes of Health Stroke (NIHSS) score (< 16 vs ≥ 16), (4) baseline ASPECTS (< 8 vs ≥ 8), (5) tandem lesions presence (yes/no), (6) Anesthesia type (local vs general). Imaging analysis and outcomes All images were independently assessed by core lab staff blinded to clinical and outcome data. Imaging assessment included early ischemic changes on non-contrast CT using Alberta Stroke Program Early CT Score (ASPECTS) for anterior circulation strokes, any intracranial hemorrhage(ICH) and symptomatic intracranial hemorrhage (sICH; according to the Heidelberg bleeding classification 18 ). The mRS is used to measure neurological function recovery following ischemic stroke, ranging from 0 to 6, with higher scores signify increasing disability, and a score of 6 indicates death. The primary outcome of our study was 90-day ordinal mRS shift. Secondary outcomes were the rates of mRS 0–1, 0–2, and 0–3, and safety outcomes were all-cause mortality at 90 days, rates of any ICH and sICH. Statistical Analysis Baseline characteristics and outcome variables of patients were analyzed, with percentages, median values, and interquartile ranges presented. Intergroup differences were assessed using the Fisher exact test for categorical variables and the Kruskal-Wallis test for continuous variables. RCS were utilized to flexibly model and visualize the relationship between PRT and the rate of favorable functional outcome. The optimal PRT cutoff was identified through multivariable logistic regression maximizing the adjusted odds ratio (aOR) for favorable functional outcome. The RCS models adjusted for pre-specified clinically relevant covariates: age, baseline NIHSS score, ASPECTS, pass number of thrombectomy and onset-puncture time. Covariate selection followed clinical plausibility rather than statistical significance to avoid overadjustment bias. Ordinal mRS shift at 90 days was analyzed using multivariable proportional odds logistic regression. secondary outcomes were modeled via logistic regression. For subgroup analysis and comparison of outcomes between patients achieving successful reperfusion beyond cutoff values and those attaining partial reperfusion, odds ratios (aOR) and their corresponding 95% confidence intervals (CIs) were calculated. A probability value of ≤ 0.05 was considered statistically significant. Statistical interaction was assessed using likelihood ratio tests comparing models with/without interaction terms. All analyses were conducted using SAS version 9.4 software (SAS Institute, Cary, NC, USA) and R 4.2.1. RESULTS Baseline characteristics and cutoff of PRT From the ANGEL-ACT Registry cohort (n = 1,793), 681 patients with anterior LVO met inclusion criteria (Fig. 1 ). Baseline characteristics stratified by 90-day functional independence (mRS 0–2 vs 3–6) was demonstrated in Table 1 . Of the 681 patients included in our study, 303 (44.5%) achieved favorable functional outcome, 397 patients (58.3%) were male, 284 patients (41.7%) were female. Restricted cubic spline (RCS) analysis adjusted for age, NIHSS, thrombectomy attempts, and onset-puncture time and 51 minutes was identified as the PRT threshold. The relationship between PRT and favorable functional outcome is provided in Fig. 2 , which demonstrated a nonlinear relationship between PRT and favorable functional outcome. A paradoxical increase in favorable functional outcome likelihood beyond 51 minutes was noted, suggesting patients can still benefit from successful reperfusion when PRT exceeds 51 minutes appropriately. Table 1 Baseline characteristics of patients included in the study Baseline characteristics mRS 0–2 (n = 303) mRS 3–6 (n = 378) P-value Male n(%) 194(64.0) 203(53.7) 0.01 Age, mean (SD), y 63.5 ± 12.0 67.6 ± 11.3 < 0.01 History of hypertension, n(%) 140(46.2) 225(59.5) < 0.01 History of diabetes mellitus, n(%) 42(13.9) 71(18.8) 0.10 History of dyslipidemia, n(%) 21(6.9) 31(8.2) 0.56 History of coronary heart disease, n(%) 43(14.2) 78(20.6) 0.03 History of atrial fibrillation/flutter, n(%) 108(35.6) 186(49.2) < 0.01 Prior ischemic stroke, n(%) 60(19.8) 98(25.9) 0.07 Cigarette smoking, n(%) 0.06 Never smoke 190(62.7) 266(70.4) Used to smoke 19(6.3) 25(6.6) Current smoker 94(31.0) 87(23.0) Alcohol drinking, n(%) 0.04 Never drink 172(56.8) 254(67.2) Occasional drink 83(27.4) 81(11.9) Current drinker 41(13.5) 34(8.9) Used to drink 7(2.3) 9(2.4) Onset-arrival time, median (IQR), min 83(50–160) 100(52–160) 0.20 NIHSS, median (IQR) 14(11–18) 18(14–22) < 0.01 ASPECTS, median (IQR) 10(8–10) 10(8–10) 0.02 Intravenous thrombolysis, n(%) 109(36.0) 129(34.1) 0.63 Antiplatelet, n(%) 46(15.2) 52(13.8) 0.66 Anticoagulant, n(%) 13(4.3) 20(5.3) 0.59 Type of anesthesia < 0.01 Local anesthesia n(%) 222(61.6) 233(73.3) General anesthesia, n(%) 81(26.7) 145(38.4) Puncture-reperfusion time, median (IQR), min 71(50–105) 90(55–135) < 0.01 Onset-reperfusion time, median (IQR), min 302(240–367) 318(269–390) < 0.01 Door-reperfusion time, median (IQR), min 184(143–240) 208(156–269) < 0.01 Final mTICI < 0.01 0-2a 17(5.6) 47(12.4) 2b-3 286(94.4) 331(87.6) Stroke subtype by TOAST criteria, n(%) < 0.01 Large artery atherosclerosis 139(46.0) 136(36.0) Cardioembolism 119(39.4) 179(47.4) Others or unknown 44(14.6) 63(16.7) Pass number of thrombectomy, median (IQR) 1(1–2) 2(1–3) < 0.01 Total number of EVT, median (IQR) 2(1–3) 2(1–3) 0.03 SD, standard deviation; IQR, interquartile range; NIHSS, National Institutes of Health Stroke Scale score; TOAST, Trial of Org 10172 in Acute Stroke Treatment; mTICI, modified Thrombolysis In Cerebral Infarction; EVT, Endovascular Treatment. Comparison of outcomes between patients achieved successful reperfusion with prolonged PRT and those achieved partial reperfusion Comparative analyses between patients achieved successful reperfusion with PRT > 51min and those achieved partial reperfusion irrespective of procedural duration was demonstrated in Table 2 . After adjusted covariates significantly different in Table 1 , no significant difference was observed in the primary outcome (aOR 0.57 [95% CI 0.26–1.23], P = 0.15). Higher mRS 0–3 rate and marginal safety benefits were noted in patients achieving successful reperfusion with prolonged PRT (PRT > 51min) (mRS 0–3: aOR 2.86 [95% CI 1.21–6.76], P = 0.02; intracranial hemorrhage: aOR 0.49 [95% CI 0.23–1.04], P = 0.06; symptomatic intracranial hemorrhage: aOR 0.38 [95% CI 0.14–1.05], P = 0.06), while the rates of primary outcome (mRS at 90 days: aOR 0.57 [95% CI 0.26–1.23], P = 0.15), mRS 0–1(aOR 1.83 [95% CI 0.74–4.54], P = 0.19), mRS 0–2(aOR 1.84 [95% CI 0.76–4.44], P = 0.17) and mortality (aOR 0.82 [95% CI 0.29–2.32], P = 0.70) were comparable. Table 2 Outcomes between patients achieving successful reperfusion with prolonged puncture-to-reperfusion time and partial reperfusion. Partial reperfusion Successful reperfusion and PRT ≥ 51 Unadjusted analysis Adjusted analysis OR (95% CI) P value OR* (95% CI) P value mRS at 90 d, median (IQR) 4(3–6) 3(0–5) 0.34(0.19–0.62) < 0.01 0.57(0.26–1.23) 0.15 mRS 0–1 at 90 d 12/60(20.0) 187/453(41.3) 2.81(1.45–5.44) < 0.01 1.83(0.74–4.54) 0.19 mRS 0–2 at 90 d 14/60(23.3) 206/453(45.5) 2.74(1.47–5.13) < 0.01 1.84(0.76–4.44) 0.17 mRS 0–3 at 90 d 20/60(33.3) 258/453(57.0) 2.65(1.50–4.67) < 0.01 2.86(1.21–6.76) 0.02 Death within 90 d 16/60(26.7) 76/453(16.8) 0.55(0.30–1.03) 0.06 0.82(0.29–2.32) 0.70 Any ICH 28/64(43.8) 121/453(26.7) 0.47(0.274–0.801) 0.01 0.49(0.23–1.04) 0.06 Symptomatic ICH ‡ 10/64(15.6) 41/449(9.1) 0.65(0.26–1.15) 0.11 0.38(0.14–1.05) 0.06 IQR, interquartile range; PRT, puncture-reperfusion time; mRS, modified Rankin Scale. ‡ Symptomatic ICH indicates symptomatic intracranial hemorrhage which is assessed according to the Heidelberg bleeding classification criteria. Subgroups analysis We also modeled the relationship between onset-to-reperfusion time and rate of favorable functional outcome to further screen subgroups which exhibited heightened sensitivity to reperfusion timing (Supplementary Fig. 1). 252 minutes was determined as the onset-to-reperfusion time cutoff. The process of screening subgroups was presented in supplementary table 1 and supplementary table 2. After onset-to-reperfusion time was dichotomized at 252 minutes, subgroups of younger age (< 65 years; aOR 0.42, 95% CI [0.19–0.92], P = 0.03), those receiving intravenous thrombolysis (aOR 0.41, 95% CI [0.17-1.00], P = 0.05), and those with higher baseline ASPECTS (≥ 8; aOR 0.58, 95% CI [0.35–0.96], P = 0.03) tended to have a higher rate of obtaining favorable functional outcome. No significant difference was noted after the puncture-to-reperfusion time was dichotomized at 51 minutes. There was no heterogeneity in the effect of prolonged onset-to-reperfusion time and puncture-to-reperfusion time on favorable functional outcomes across age, intravenous thrombolysis, baseline NIHSS or ASPECT score, presence of tandem lesions, type of anesthesia, and successful reperfusion. Key subgroups comparison of outcomes between patients achieved successful reperfusion with prolonged PRT and those achieved partial reperfusion Key subgroups comparison of the primary, secondary and safety outcomes between patients achieving successful reperfusion with prolonged PRT and those with partial reperfusion irrespective of procedural duration was presented in Table 3 . In the age < 65 subgroup, patients achieving successful reperfusion with prolonged PRT had a higher rate of obtaining mRS 0–3 (aOR 5.03, 95% CI [1.16–21.83], P = 0.03), while no significant differences were observed in rates of primary outcome (mRS at 90 days; aOR 0.41 [95% CI 0.10–1.59], P = 0.20), mRS 0–1(aOR 2.09 [95% CI 0.46–9.57], P = 0.34), mRS 0–2(aOR 2.56 [95% CI 0.56–11.57], P = 0.22) and safety outcomes(mortality: aOR 0.51, 95% CI 0.10–2.69; P = 0.43; ICH: aOR 0.31, 95% CI [0.08–1.28], P = 0.11; sICH: aOR 0.37, 95% CI 0.07–2.02; P = 0.25). In the intravenous thrombolysis subgroup, significantly lower rates of any intracranial hemorrhage and symptomatic hemorrhage were observed in patients achieving successful reperfusion with prolonged PRT (aOR 0.13, 95% CI [0.02–0.73], P = 0.02; aOR 0.13, 95% CI [0.02–0.76], P = 0.02 respectively), whereas no differences were observed in primary outcome (mRS at 90 days; aOR 0.73 [95% CI 0.16–3.23], P = 0.67), secondary outcomes (mRS 0–1: aOR 1.34 [95% CI 0.21–8.62], P = 0.76; mRS 0–2: aOR 1.70 [95% CI 0.26–10.93], P = 0.58; mRS 0–3: aOR 2.67 [95% CI 0.40-17.68], P = 0.31) and mortality (aOR 0.14 [95% CI 0.01–2.47] P = 0.18). In the ASPECTS ≥ 8 Subgroup, All outcomes were comparable between groups. Table 3 Outcomes of subgroups between patients achieving successful reperfusion with prolonged puncture-to-reperfusion time and partial reperfusion. Partial reperfusion Successful reperfusion and PRT ≥ 51 Unadjusted analysis Adjusted analysis OR (95% CI) P value OR* (95% CI) P value Age<65 subgroup mRS at 90 d, median (IQR) 4(3–5) 1(0–4) 0.27(0.11–0.66) < 0.01 0.41(0.10–1.59) 0.20 mRS 0–1 at 90 d 6/25(24.0) 135/257(52.5) 3.50(1.36–9.06) 0.01 2.09(0.46–9.57) 0.34 mRS 0–2 at 90 d 6/25(24.0) 149/257(58.0) 4.37(1.69–11.30) < 0.01 2.56(0.56–11.57) 0.22 mRS 0–3 at 90 d 11/25(44.0) 182/257(70.8) 3.09(1.34–7.11) 0.01 5.03(1.16–21.83) 0.03 Death within 90 d 5/25(20.0) 28/257(10.9) 0.49(0.17–1.41) 0.18 0.51(0.10–2.69) 0.43 Any ICH 12/26(46.2) 55/252(21.8) 0.33(0.14–0.75) 0.01 0.31(0.08–1.28) 0.11 Symptomatic ICH ‡ 4/26(15.4) 20/252(7.9) 0.47(0.15–1.51) 0.21 0.37(0.07–2.02) 0.25 Intravenous thrombolysis subgroup mRS at 90 d, median (IQR) 4(1–4) 3(0–4) 0.63(0.22–1.84) 0.40 0.73(0.16–3.23) 0.67 mRS 0–1 at 90 d 6/18(33.3) 97/220(44.1) 1.58(0.57–4.35) 0.38 1.34(0.21–8.62) 0.76 mRS 0–2 at 90 d 6/18(33.3) 103/220(46.8) 1.76(0.64–4.86) 0.27 1.70(0.26–10.93) 0.58 mRS 0–3 at 90 d 7/18(38.9) 129/220(58.6) 2.23(0.83–5.96) 0.11 2.67(0.40-17.68) 0.31 Death within 90 d 2/18(11.1) 30/220(13.6) 1.26(0.28–5.77) 0.76 0.14(0.01–2.47) 0.18 Any ICH 10/20(50.0) 57/216(26.0) 0.35(0.14–0.89) 0.03 0.13(0.02–0.73) 0.02 Symptomatic ICH ‡ 5/20(25.0) 19/217(8.8) 0.29(0.09–0.88) 0.03 0.13(0.02–0.76) 0.02 ASPECTS ≥ 8 subgroup mRS at 90 d, median (IQR) 4(1–5) 3(0–5) 0.44(0.21–0.91) 0.03 0.88(0.32–2.42) 0.81 mRS 0–1 at 90 d 12/41(29.3) 193/427(45.2) 1.99(0.99–4.01) 0.05 1.08(0.34–3.42) 0.90 mRS 0–2 at 90 d 14/41(34.2) 208/427(48.7) 1.83(0.94–3.59) 0.08 1.12(0.36–3.44) 0.84 mRS 0–3 at 90 d 18/41(43.9) 250/427(58.6) 1.81(0.95–3.44) 0.07 1.74(0.56–5.43) 0.34 Death within 90 d 10/41(24.4) 67/427(15.7) 0.58(0.27–1.23) 0.16 1.29(0.22–7.45) 0.78 Any ICH 15/44(34.1) 102/423(24.1) 0.61(0.32–1.19) 0.15 0.97(0.34–2.80) 0.96 Symptomatic ICH ‡ 3/44(6.8) 36/418(8.6) 1.29(0.38–4.37) 0.68 0.66(0.14–3.04) 0.59 IQR, interquartile range; PRT, puncture-reperfusion time; mRS, modified Rankin Scale. ‡ Symptomatic ICH indicates symptomatic intracranial hemorrhage which is assessed according to the Heidelberg bleeding classification criteria. Discussion Our study suggests that PRT as an easily accessible variable, could be a crucial indicator for procedural termination. Extending procedural duration beyond the 51-minute PRT threshold may yield clinical benefits, particularly in younger patients, while limited efficacy were indicated in intravenous thrombolysis-treated patients and baseline ASPECTS ≥ 8 patients. We believe this is a crucial exploration as this individualized termination protocols can directly impact the clinical decision-making process in the field of acute ischemic stroke due to LVO. Aside from PRT, the optimal number of thrombectomy attempts has been extensively investigated as a key determinant of EVT efficacy. In the process of our clinical practice, when successful reperfusion is hard to achieve, the number of thrombectomy attempt could be a key factor to be taken into account based on current evidence. Contemporary evidence suggests diminishing clinical outcomes when exceeding three retrieval attempts for ischemic stroke due to anterior LVO 15 , 19 , 20 , a threshold balancing successful reperfusion against procedural risks as repeated thrombectomy induce blood-brain barrier disruption, elevating intracranial hemorrhage risk, while simultaneously reducing recanalization probabilities due to refractory thrombi and distal embolization 21 . However, retrieval attempt limits may not suit all clinical contexts, bailout angioplasty - including balloon dilation and stent implantation – is needed in atherosclerosis lesion, adjunctive techniques are also needed for tortuous access to the occlusion site, such standard undermines the necessity for operator flexibility in complex cases. Moreover, there are studies suggest that the establishment of arbitrary thrombectomy pass count thresholds may lead to early termination of EVT 22 . Our findings demonstrate a nonlinear relationship between PRT and functional independence (mRS 0–2). Beyond the 51-minute threshold, a transient increase in favorable outcomes is observed. However, this benefit diminishes with time elapsing. This underscores the necessity for individualized protocols. Jia et al suggested that in patients with failed thrombectomy attributable to non-mechanical factors (e.g., access challenges or refractory thrombus), prolonging procedural duration to implement strategies to access occlusion site may confer enhanced clinical benefits in functional recovery 23 . However, this benefit doesn’t exist persistently. There is evidence indicates that PRT exceeding 60 minutes yields diminishing benefits, regardless of thrombectomy attempts 12 . This phenomenon implies that prolonged time spent on recanalization – even when followed by successful recanalization – may negate therapeutic benefits. In our study, subgroup analysis of onset-to-reperfusion time revealed distinct time-sensitivity across patient subgroups: patients with younger age, higher ASPECTS, and the administration of intravenous thrombolysis are less likely to achieve a favorable functional outcome as the time to reperfusion increases. Notably, this time-sensitivity was absent when analyzing PRT across all subgroups. This finding may be explained by the fact that onset-to-reperfusion time encapsulates total ischemic duration from symptom onset, directly correlating with neuronal salvage potential, while PRT isolates procedural duration, a small portion of onset-to-puncture time. Thus, the time-sensitive nature is more prominent in onset-to-reperfusion time rather than PRT. Several factors may explain why these populations are more sensitive to time to reperfusion. In younger patients, less atherosclerosis and a higher likelihood of cardiogenic thrombus are common 24 , where limited collaterals accelerate infarct growth. In patients receiving intravenous thrombolysis, early recanalization creates larger penumbra 25 , 26 , heightening vulnerability to delayed successful reperfusion. Patients with higher ASPECTS (≥ 8) also have larger penumbra. Notably, in the intravenous thrombolysis subgroup, patients achieving partial reperfusion demonstrated significantly higher rates of ICH and sICH, this can be explained from the following aspects: (1) partial reperfusion patients is associated with larger final infarct core volumes compared to those achieved successful reperfusion 27 , 28 . (2) Thrombolytic-induced clot disruption and distal embolization of fragments necessitate increased thrombectomy attempts, a process that induces endothelial damage and consequently elevates hemorrhagic risk 29 , 30 . This phenomenon underscores the need for early procedural termination decisions in bridging therapy patients when complete recanalization proves challenging. This study is the first to establish a 51-minute puncture-to-reperfusion time (PRT) threshold using restricted cubic spline analysis in a multicenter cohort. Contrary to the prevailing "the sooner, the better" doctrine, our data reveal a transient therapeutic window where persistent recanalization attempts improve favorable functional outcome rate in challenging cases. This challenges the universality of fixed time cutoffs in clinical practice. Through subgroup analysis, we also identified potential populations who may and may not benefit from extended procedural duration. Moreover, using PRT threshold to guide procedural termination decision underscores operator flexibility in challenging cases. The limitations of our study are as follows. First, the retrospective analysis of the ANGEL-ACT registry introduces potential selection bias. Second, key prognostic variables, including detailed collateral circulation status (e.g., ASITN/SIR scores) and thrombus composition analysis, were not systematically collected. Third, the limited sample size in subgroup comparison prompts the interpretation of the results should be cautious. Forth, all participants of ANGEL-ACT registry are Chinese, the high percentage of ICAD in the Chinese population may confound the conclusions and may not be applied to other populations. Conclusion Patients could benefit from successful reperfusion when PRT exceeds 51 minutes, particularly for younger patients (<65 years), while patients received intravenous thrombolysis and patients with ASPECTS≥8 may not. Individualized termination protocols are needed, further validation is warranted prior to clinical implementation. Declarations Acknowledgements We thank all participating hospitals, relevant clinicians, statisticians, and imaging and laboratory technicians. Author Contributions ZM designed, led the study and had full access to all of the data in the study and took responsibility for the integrity of the data and the accuracy of the data analysis. ZY and FC prepared the first draft of the report, WL made revisions of draft. All authors critically reviewed the report and approved the final version. All authors critically reviewed the report and approved the final version. Additional Information Disclosures None. Funding This study is supported by National Key Research and Development Program of China (2016 YFC1301500). Ethical approval All procedures performed in studies involving human participants were in accordance with the 1964 Helsinki declaration and its later amendments or comparable ethical standards. The protocol and data collection were approved by the ethics committees of Beijing Tiantan Hospital and each participating site. Each participant or his/her legal representative gave written informed consent before being enrolled in the study. This article does not contain any studies with animals performed by any of the authors. Consent to Participate Individual patients’ written informed consent was waived owing to the retrospective nature of the study. Conflict of interest The authors declare no competing interests. Data availability statement Anonymized data not published in this article are available from the corresponding author on reasonable request. References Berkhemer, O. A. et al. A Randomized Trial of Intraarterial Treatment for Acute Ischemic Stroke. New England Journal of Medicine 372 , 11-20 https://doi.org/10.1056/NEJMoa1411587 (2015). Campbell, B. C. V. et al. Endovascular Therapy for Ischemic Stroke with Perfusion-Imaging Selection. 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Association Between Time to Treatment With Endovascular Reperfusion Therapy and Outcomes in Patients With Acute Ischemic Stroke Treated in Clinical Practice. Jama 322 https://doi.org/10.1001/jama.2019.8286 (2019). Alawieh, A. et al. Impact of Procedure Time on Outcomes of Thrombectomy for Stroke. Journal of the American College of Cardiology 73 , 879-890 https://doi.org/10.1016/j.jacc.2018.11.052 (2019). Saver, J. L. et al. Time to Treatment With Endovascular Thrombectomy and Outcomes From Ischemic Stroke: A Meta-analysis. Jama 316 https://doi.org/10.1001/jama.2016.13647 (2016). Flottmann, F. et al. Recanalization Rate per Retrieval Attempt in Mechanical Thrombectomy for Acute Ischemic Stroke. Stroke 49 , 2523-2525 https://doi.org/10.1161/strokeaha.118.022737 (2018). García-Tornel, Á. et al. When to Stop. Stroke 50 , 1781-1788 https://doi.org/10.1161/strokeaha.119.025088 (2019). Seker, F. et al. Correlation of Thrombectomy Maneuver Count with Recanalization Success and Clinical Outcome in Patients with Ischemic Stroke. American Journal of Neuroradiology 38 , 1368-1371 https://doi.org/10.3174/ajnr.A5212 (2017). Jia, B. et al. Current Status of Endovascular Treatment for Acute Large Vessel Occlusion in China. Stroke 52 , 1203-1212 https://doi.org/10.1161/strokeaha.120.031869 (2021). von Kummer, R. et al. The Heidelberg Bleeding Classification. Stroke 46 , 2981-2986 https://doi.org/10.1161/strokeaha.115.010049 (2015). Flottmann, F. et al. Good Clinical Outcome Decreases With Number of Retrieval Attempts in Stroke Thrombectomy. Stroke 52 , 482-490 https://doi.org/10.1161/strokeaha.120.029830 (2021). Filioglo, A. et al. More than five stentriever passes: real benefit or futile recanalization? Neuroradiology 62 , 1335-1340 https://doi.org/10.1007/s00234-020-02469-x (2020). Luby, M. et al. Frequency of Blood-Brain Barrier Disruption Post-Endovascular Therapy and Multiple Thrombectomy Passes in Acute Ischemic Stroke Patients. Stroke 50 , 2241-2244 https://doi.org/10.1161/strokeaha.119.025914 (2019). Mohammaden, M. H. et al. Lack of Reperfusion Rather Than Number of Passes Defines Futility in Stroke Thrombectomy: A Matched Case-Control Study. Stroke 52 , 2757-2763 https://doi.org/10.1161/strokeaha.120.033539 (2021). Jia, B. et al. Rescue angioplasty and/or stenting after mechanical thrombectomy: who can benefit? Journal of NeuroInterventional Surgery 16 , 1360-1367 https://doi.org/10.1136/jnis-2023-020824 (2024). Perera, K. S. et al. Evaluating Rates of Recurrent Ischemic Stroke Among Young Adults With Embolic Stroke of Undetermined Source. JAMA Neurology 79 https://doi.org/10.1001/jamaneurol.2022.0048 (2022). Majoie, C. B. et al. Value of intravenous thrombolysis in endovascular treatment for large-vessel anterior circulation stroke: individual participant data meta-analysis of six randomised trials. The Lancet 402 , 965-974 https://doi.org/10.1016/s0140-6736(23)01142-x (2023). Seners, P. et al. Arterial Recanalization During Interhospital Transfer for Thrombectomy. Stroke 55 , 1525-1534 https://doi.org/10.1161/strokeaha.124.046694 (2024). Cappellari, M. et al. IER-SICH Nomogram to Predict Symptomatic Intracerebral Hemorrhage After Thrombectomy for Stroke. Stroke 50 , 909-916 https://doi.org/10.1161/strokeaha.118.023316 (2019). van der Steen, W. et al. Determinants of Symptomatic Intracranial Hemorrhage After Endovascular Stroke Treatment: A Retrospective Cohort Study. Stroke 53 , 2818-2827 https://doi.org/10.1161/strokeaha.121.036195 (2022). Tong, X. et al. Thrombectomy Versus Combined Thrombolysis and Thrombectomy in Patients With Acute Stroke. Stroke 52 , 1589-1600 https://doi.org/10.1161/strokeaha.120.031599 (2021). Ren, Y. et al. Clot Migration Is Associated With Intravenous Thrombolysis in the Setting of Acute Ischemic Stroke. Stroke 49 , 3060-3062 https://doi.org/10.1161/strokeaha.118.022751 (2018). Additional Declarations No competing interests reported. Supplementary Files Supplementarymaterial.docx Cite Share Download PDF Status: Posted Version 1 posted 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. We do this by developing innovative software and high quality services for the global research community. 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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-6332896","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Article","associatedPublications":[],"authors":[{"id":453974797,"identity":"9d7ee431-60f4-487b-864b-55794059c382","order_by":0,"name":"Zequan Yu","email":"","orcid":"","institution":"Department of Neurology, Beijing Haidian Hospital","correspondingAuthor":false,"prefix":"","firstName":"Zequan","middleName":"","lastName":"Yu","suffix":""},{"id":453974799,"identity":"d02c1c11-cc51-41c3-8e7a-090ba25020b3","order_by":1,"name":"Fangguang Chen","email":"","orcid":"","institution":"Department of Interventional Neuroradiology, Beijing Tiantan Hospital, Capital Medical University, Beijing, China","correspondingAuthor":false,"prefix":"","firstName":"Fangguang","middleName":"","lastName":"Chen","suffix":""},{"id":453974801,"identity":"889bb436-4d25-497c-8617-6329f4e43535","order_by":2,"name":"Hao Feng","email":"","orcid":"","institution":"Department of Neurology, Beijing Haidian Hospital","correspondingAuthor":false,"prefix":"","firstName":"Hao","middleName":"","lastName":"Feng","suffix":""},{"id":453974803,"identity":"0c7c5539-3674-4075-8f09-8bfd733e2656","order_by":3,"name":"Xiaobing Li","email":"","orcid":"","institution":"Department of Neurology, Beijing Haidian Hospital","correspondingAuthor":false,"prefix":"","firstName":"Xiaobing","middleName":"","lastName":"Li","suffix":""},{"id":453974804,"identity":"d8dfdc4d-d7fa-4601-a1c6-f27afd36a4a1","order_by":4,"name":"Wei Liu","email":"","orcid":"","institution":"Department of Neurology, Beijing Haidian Hospital","correspondingAuthor":false,"prefix":"","firstName":"Wei","middleName":"","lastName":"Liu","suffix":""},{"id":453974805,"identity":"fde59d6e-046c-45fc-b514-4dd89ec062cd","order_by":5,"name":"Zhongrong Miao","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAA0ElEQVRIiWNgGAWjYDACCTiL+cCBDz9I08KWeHBmD2laeIwPc7ARoUN+dvOxh1/32OTJh535cJiBh0GeX+wAfi2Mc46lG8s8Sys2vJ274XCBBYPhzNkJ+LUwS+SYSUscOJy4cTZQywwehgSD2wS0sCG05Dw4zMNGhBYeoBbJD0At86VzGIjTIiGRlibNcCAtcYN0mgEwkCUI+0V+RvIxyR8HbBLnz05+/OHDDxt5fmkCWkCAmQdIGByA2EpYOQgwgpKJfANxikfBKBgFo2AEAgD5M0Z4SERvmAAAAABJRU5ErkJggg==","orcid":"","institution":"Department of Interventional Neuroradiology, Beijing Tiantan Hospital, Capital Medical University, Beijing, China","correspondingAuthor":true,"prefix":"","firstName":"Zhongrong","middleName":"","lastName":"Miao","suffix":""}],"badges":[],"createdAt":"2025-03-29 08:38:16","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-6332896/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-6332896/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":82582996,"identity":"e99ef46b-ead9-45e1-9d14-034d0d7a6b03","added_by":"auto","created_at":"2025-05-13 06:47:42","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":368627,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eFlowchart shows the selection of patients in the study\u003c/strong\u003e\u003c/p\u003e","description":"","filename":"floatimage1.png","url":"https://assets-eu.researchsquare.com/files/rs-6332896/v1/5cfd53ce58a2b0defe441452.png"},{"id":82582999,"identity":"8d346cb2-16a3-491b-8273-ef7b77d8bd55","added_by":"auto","created_at":"2025-05-13 06:47:42","extension":"png","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":195696,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eThe relationship between PRT and favorable functional outcome\u003c/strong\u003e\u003c/p\u003e","description":"","filename":"floatimage2.png","url":"https://assets-eu.researchsquare.com/files/rs-6332896/v1/bce17add6713959b198c8678.png"},{"id":84699917,"identity":"e2844ddd-f629-44f0-bead-4e0dc57d11d3","added_by":"auto","created_at":"2025-06-16 11:17:07","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":1797808,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-6332896/v1/7d7f5b91-3f8c-4b55-b625-0b7d662f6df0.pdf"},{"id":82583000,"identity":"44cd193e-1baf-4e53-9ca8-fb9338b6c5db","added_by":"auto","created_at":"2025-05-13 06:47:42","extension":"docx","order_by":0,"title":"","display":"","copyAsset":false,"role":"supplement","size":441837,"visible":true,"origin":"","legend":"","description":"","filename":"Supplementarymaterial.docx","url":"https://assets-eu.researchsquare.com/files/rs-6332896/v1/06337e45b44c57ac5ab5a0d1.docx"}],"financialInterests":"No competing interests reported.","formattedTitle":"Puncture-to-Reperfusion Time Threshold Guides Procedural Termination in Thrombectomy: Analysis from the ANGEL-ACT Registry","fulltext":[{"header":"Introduction","content":"\u003cp\u003eEndovascular treatment (EVT) has been established as the first-line therapy for acute ischemic stroke caused by large vessel occlusion (LVO)\u003csup\u003e\u003cspan additionalcitationids=\"CR2 CR3 CR4 CR5 CR6\" citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e\u003c/sup\u003e. However, 41\u0026ndash;43% of patients fail to achieve favorable functional outcomes (modified Rankin Scale [mRS] 0\u0026ndash;2) despite successful recanalization, a clinical conundrum termed futile recanalization\u003csup\u003e\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e\u003c/sup\u003e. While multiple determinants contribute to this phenomenon, including collateral status, infarct core volume, and reperfusion injury, procedural duration, quantified by puncture-to-reperfusion time (PRT), has emerged as a critical modifiable predictor of clinical outcomes\u003csup\u003e\u003cspan additionalcitationids=\"CR10\" citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e\u003c/sup\u003e. Prolonged PRT not only correlates with escalating rate of complication but also diminishes the likelihood of meaningful neurological improvement\u003csup\u003e\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e\u003c/sup\u003e. The HERMES collaboration consensus advocates PRT\u0026thinsp;\u0026le;\u0026thinsp;60 minutes an optimal threshold\u003csup\u003e\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e\u003c/sup\u003e. However, this consensus faces profound implementation challenges in clinical practice. In technically challenging cases, characterized by tortuous access to the occlusion site, refractory thrombi, or tandem occlusions, adjunctive techniques and iterative thrombectomy attempts are needed, inevitably prolonging PRT beyond recommended threshold. This operational reality creates a therapeutic dilemma: clinicians must balance the diminishing therapeutic efficacy of eventual successful recanalization against the risks of prematurely terminating recanalization.\u003c/p\u003e \u003cp\u003eThere are many studies linking excessive thrombectomy attempts to attenuated clinical benefit\u003csup\u003e\u003cspan additionalcitationids=\"CR15\" citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e\u003c/sup\u003e, however, such standard fails to apply when adjunctive techniques are needed, which undermined the necessity for operator flexibility. Current guidelines provide limited consensus on termination criteria for persistently unsuccessful thrombectomy attempts. Crucially, the prognostic value of PRT threshold as a potential termination indicator remains underexplored. This study hypothesizes that the therapeutic time window for PRT exhibits population-specific boundaries, beyond which continued thrombectomy attempts offset the potential benefits of successful recanalization. We aim to (1) identify the PRT threshold predictive of futile recanalization, and (2) delineate patient subgroups that may or may not benefit from extended procedural duration.\u003c/p\u003e"},{"header":"METHODS","content":"\u003cdiv id=\"Sec3\" class=\"Section2\"\u003e \u003ch2\u003eStudy population and study design\u003c/h2\u003e \u003cp\u003eWe conducted a retrospective analysis of the Endovascular Treatment Key Technique and Emergency Workflow Improvement of Acute Ischemic Stroke (ANGEL-ACT) Registry, a prospective multicenter registry (ClinicalTrial.gov ID: NCT03370939), which consecutively enrolled 1793 acute ischemic stroke patients receiving endovascular reperfusion therapy across 111 Chinese centers (November 2017 to March 2019). Detailed inclusion and exclusion criteria have been previously documented\u003csup\u003e\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e\u003c/sup\u003e. Written informed consent was obtained from all patients or their legally authorized representatives. A group of patients was identified from this registry. Inclusion criteria are ischemic stroke due to anterior LVO confirmed by CTA/MRA/DSA, onset-puncture time\u0026thinsp;\u0026le;\u0026thinsp;6 hours, baseline ASPECTS\u0026thinsp;\u0026ge;\u0026thinsp;6 on non-contrast CT. Successful reperfusion was assessed using the modified thrombolysis in cerebral infarction (mTICI) scale, mTICI 2b-3 indicated successful reperfusion, while an mTICI score of 0-2a indicated partial reperfusion. Restricted cubic spline (RCS) with 3 knots (10th, 50th, 90th percentiles) were implemented to model nonlinear relationships between PRT and favorable functional outcome and to determine the cutoff value of PRT, the optimal PRT threshold was determined by maximizing the adjusted odds ratio (aOR) in multivariable logistic regression. Patients achieving successful reperfusion beyond the PRT threshold were compared to those with partial reperfusion irrespective of procedural duration. Subgroup analyses were also performed based on the following factors: (1) Age (\u0026lt;\u0026thinsp;65 vs\u0026thinsp;\u0026ge;\u0026thinsp;65 years), (2) intravenous thrombolysis (yes/no), (3) baseline National Institutes of Health Stroke (NIHSS) score (\u0026lt;\u0026thinsp;16 vs\u0026thinsp;\u0026ge;\u0026thinsp;16), (4) baseline ASPECTS (\u0026lt;\u0026thinsp;8 vs\u0026thinsp;\u0026ge;\u0026thinsp;8), (5) tandem lesions presence (yes/no), (6) Anesthesia type (local vs general).\u003c/p\u003e \u003c/div\u003e\n\u003ch3\u003eImaging analysis and outcomes\u003c/h3\u003e\n\u003cp\u003eAll images were independently assessed by core lab staff blinded to clinical and outcome data. Imaging assessment included early ischemic changes on non-contrast CT using Alberta Stroke Program Early CT Score (ASPECTS) for anterior circulation strokes, any intracranial hemorrhage(ICH) and symptomatic intracranial hemorrhage (sICH; according to the Heidelberg bleeding classification\u003csup\u003e\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e\u003c/sup\u003e).\u003c/p\u003e \u003cp\u003eThe mRS is used to measure neurological function recovery following ischemic stroke, ranging from 0 to 6, with higher scores signify increasing disability, and a score of 6 indicates death. The primary outcome of our study was 90-day ordinal mRS shift. Secondary outcomes were the rates of mRS 0\u0026ndash;1, 0\u0026ndash;2, and 0\u0026ndash;3, and safety outcomes were all-cause mortality at 90 days, rates of any ICH and sICH.\u003c/p\u003e \u003cdiv id=\"Sec5\" class=\"Section2\"\u003e \u003ch2\u003eStatistical Analysis\u003c/h2\u003e \u003cp\u003eBaseline characteristics and outcome variables of patients were analyzed, with percentages, median values, and interquartile ranges presented. Intergroup differences were assessed using the Fisher exact test for categorical variables and the Kruskal-Wallis test for continuous variables. RCS were utilized to flexibly model and visualize the relationship between PRT and the rate of favorable functional outcome. The optimal PRT cutoff was identified through multivariable logistic regression maximizing the adjusted odds ratio (aOR) for favorable functional outcome. The RCS models adjusted for pre-specified clinically relevant covariates: age, baseline NIHSS score, ASPECTS, pass number of thrombectomy and onset-puncture time. Covariate selection followed clinical plausibility rather than statistical significance to avoid overadjustment bias. Ordinal mRS shift at 90 days was analyzed using multivariable proportional odds logistic regression. secondary outcomes were modeled via logistic regression. For subgroup analysis and comparison of outcomes between patients achieving successful reperfusion beyond cutoff values and those attaining partial reperfusion, odds ratios (aOR) and their corresponding 95% confidence intervals (CIs) were calculated. A probability value of \u0026le;\u0026thinsp;0.05 was considered statistically significant. Statistical interaction was assessed using likelihood ratio tests comparing models with/without interaction terms. All analyses were conducted using SAS version 9.4 software (SAS Institute, Cary, NC, USA) and R 4.2.1.\u003c/p\u003e \u003c/div\u003e"},{"header":"RESULTS","content":"\u003cdiv id=\"Sec7\" class=\"Section2\"\u003e \u003ch2\u003eBaseline characteristics and cutoff of PRT\u003c/h2\u003e \u003cp\u003eFrom the ANGEL-ACT Registry cohort (n\u0026thinsp;=\u0026thinsp;1,793), 681 patients with anterior LVO met inclusion criteria (Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003e). Baseline characteristics stratified by 90-day functional independence (mRS 0\u0026ndash;2 vs 3\u0026ndash;6) was demonstrated in Table \u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e. Of the 681 patients included in our study, 303 (44.5%) achieved favorable functional outcome, 397 patients (58.3%) were male, 284 patients (41.7%) were female. Restricted cubic spline (RCS) analysis adjusted for age, NIHSS, thrombectomy attempts, and onset-puncture time and 51 minutes was identified as the PRT threshold. The relationship between PRT and favorable functional outcome is provided in Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003e, which demonstrated a nonlinear relationship between PRT and favorable functional outcome. A paradoxical increase in favorable functional outcome likelihood beyond 51 minutes was noted, suggesting patients can still benefit from successful reperfusion when PRT exceeds 51 minutes appropriately.\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab1\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 1\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eBaseline characteristics of patients included in the study\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"4\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eBaseline characteristics\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003emRS 0\u0026ndash;2\u003c/p\u003e \u003cp\u003e(n\u0026thinsp;=\u0026thinsp;303)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003emRS 3\u0026ndash;6\u003c/p\u003e \u003cp\u003e(n\u0026thinsp;=\u0026thinsp;378)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003eP-value\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMale n(%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e194(64.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e203(53.7)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.01\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAge, mean (SD), y\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e63.5\u0026thinsp;\u0026plusmn;\u0026thinsp;12.0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e67.6\u0026thinsp;\u0026plusmn;\u0026thinsp;11.3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.01\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eHistory of hypertension, n(%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e140(46.2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e225(59.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.01\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eHistory of diabetes mellitus, n(%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e42(13.9)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e71(18.8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.10\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eHistory of dyslipidemia, n(%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e21(6.9)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e31(8.2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.56\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eHistory of coronary heart disease, n(%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e43(14.2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e78(20.6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.03\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eHistory of atrial fibrillation/flutter, n(%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e108(35.6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e186(49.2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.01\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePrior ischemic stroke, n(%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e60(19.8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e98(25.9)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.07\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCigarette smoking, n(%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.06\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNever smoke\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e190(62.7)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e266(70.4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eUsed to smoke\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e19(6.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e25(6.6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCurrent smoker\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e94(31.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e87(23.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAlcohol drinking, n(%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.04\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNever drink\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e172(56.8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e254(67.2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eOccasional drink\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e83(27.4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e81(11.9)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCurrent drinker\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e41(13.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e34(8.9)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eUsed to drink\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e7(2.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e9(2.4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eOnset-arrival time, median (IQR), min\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e83(50\u0026ndash;160)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e100(52\u0026ndash;160)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.20\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNIHSS, median (IQR)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e14(11\u0026ndash;18)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e18(14\u0026ndash;22)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.01\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eASPECTS, median (IQR)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e10(8\u0026ndash;10)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e10(8\u0026ndash;10)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.02\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eIntravenous thrombolysis, n(%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e109(36.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e129(34.1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.63\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAntiplatelet, n(%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e46(15.2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e52(13.8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.66\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAnticoagulant, n(%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e13(4.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e20(5.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.59\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eType of anesthesia\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.01\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eLocal anesthesia n(%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e222(61.6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e233(73.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eGeneral anesthesia, n(%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e81(26.7)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e145(38.4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePuncture-reperfusion time, median (IQR), min\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e71(50\u0026ndash;105)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e90(55\u0026ndash;135)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.01\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eOnset-reperfusion time, median (IQR), min\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e302(240\u0026ndash;367)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e318(269\u0026ndash;390)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.01\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eDoor-reperfusion time, median (IQR), min\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e184(143\u0026ndash;240)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e208(156\u0026ndash;269)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.01\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eFinal mTICI\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.01\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e0-2a\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e17(5.6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e47(12.4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e2b-3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e286(94.4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e331(87.6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eStroke subtype by TOAST criteria, n(%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.01\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eLarge artery atherosclerosis\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e139(46.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e136(36.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCardioembolism\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e119(39.4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e179(47.4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eOthers or unknown\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e44(14.6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e63(16.7)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePass number of thrombectomy, median (IQR)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1(1\u0026ndash;2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e2(1\u0026ndash;3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.01\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eTotal number of EVT, median (IQR)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e2(1\u0026ndash;3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e2(1\u0026ndash;3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.03\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003ctfoot\u003e \u003ctr\u003e\u003ctd colspan=\"4\"\u003eSD, standard deviation; IQR, interquartile range; NIHSS, National Institutes of Health Stroke Scale score; TOAST, Trial of Org 10172 in Acute Stroke Treatment; mTICI, modified Thrombolysis In Cerebral Infarction; EVT, Endovascular Treatment.\u003c/td\u003e\u003c/tr\u003e \u003c/tfoot\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003e \u003cb\u003eComparison of outcomes between patients achieved successful reperfusion with prolonged PRT and those achieved partial reperfusion\u003c/b\u003e \u003c/p\u003e \u003cp\u003eComparative analyses between patients achieved successful reperfusion with PRT\u0026thinsp;\u0026gt;\u0026thinsp;51min and those achieved partial reperfusion irrespective of procedural duration was demonstrated in Table \u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e. After adjusted covariates significantly different in Table \u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e, no significant difference was observed in the primary outcome (aOR 0.57 [95% CI 0.26\u0026ndash;1.23], P\u0026thinsp;=\u0026thinsp;0.15). Higher mRS 0\u0026ndash;3 rate and marginal safety benefits were noted in patients achieving successful reperfusion with prolonged PRT (PRT\u0026thinsp;\u0026gt;\u0026thinsp;51min) (mRS 0\u0026ndash;3: aOR 2.86 [95% CI 1.21\u0026ndash;6.76], P\u0026thinsp;=\u0026thinsp;0.02; intracranial hemorrhage: aOR 0.49 [95% CI 0.23\u0026ndash;1.04], P\u0026thinsp;=\u0026thinsp;0.06; symptomatic intracranial hemorrhage: aOR 0.38 [95% CI 0.14\u0026ndash;1.05], P\u0026thinsp;=\u0026thinsp;0.06), while the rates of primary outcome (mRS at 90 days: aOR 0.57 [95% CI 0.26\u0026ndash;1.23], P\u0026thinsp;=\u0026thinsp;0.15), mRS 0\u0026ndash;1(aOR 1.83 [95% CI 0.74\u0026ndash;4.54], P\u0026thinsp;=\u0026thinsp;0.19), mRS 0\u0026ndash;2(aOR 1.84 [95% CI 0.76\u0026ndash;4.44], P\u0026thinsp;=\u0026thinsp;0.17) and mortality (aOR 0.82 [95% CI 0.29\u0026ndash;2.32], P\u0026thinsp;=\u0026thinsp;0.70) were comparable.\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab2\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 2\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eOutcomes between patients achieving successful reperfusion with prolonged puncture-to-reperfusion time and partial reperfusion.\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"7\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c6\" colnum=\"6\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c7\" colnum=\"7\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colname=\"c2\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003ePartial reperfusion\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003eSuccessful reperfusion and PRT\u0026thinsp;\u0026ge;\u0026thinsp;51\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colspan=\"2\" nameend=\"c5\" namest=\"c4\"\u003e \u003cp\u003eUnadjusted analysis\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colspan=\"2\" nameend=\"c7\" namest=\"c6\"\u003e \u003cp\u003eAdjusted analysis\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003eOR (95% CI)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c5\"\u003e \u003cp\u003eP value\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c6\"\u003e \u003cp\u003eOR* (95% CI)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c7\"\u003e \u003cp\u003eP value\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003emRS at 90 d, median (IQR)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e4(3\u0026ndash;6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e3(0\u0026ndash;5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.34(0.19\u0026ndash;0.62)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.01\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e0.57(0.26\u0026ndash;1.23)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e \u003cp\u003e0.15\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003emRS 0\u0026ndash;1 at 90 d\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e12/60(20.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e187/453(41.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e2.81(1.45\u0026ndash;5.44)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.01\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e1.83(0.74\u0026ndash;4.54)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e \u003cp\u003e0.19\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003emRS 0\u0026ndash;2 at 90 d\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e14/60(23.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e206/453(45.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e2.74(1.47\u0026ndash;5.13)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.01\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e1.84(0.76\u0026ndash;4.44)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e \u003cp\u003e0.17\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003emRS 0\u0026ndash;3 at 90 d\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e20/60(33.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e258/453(57.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e2.65(1.50\u0026ndash;4.67)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.01\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e2.86(1.21\u0026ndash;6.76)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e \u003cp\u003e0.02\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eDeath within 90 d\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e16/60(26.7)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e76/453(16.8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.55(0.30\u0026ndash;1.03)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.06\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e0.82(0.29\u0026ndash;2.32)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e \u003cp\u003e0.70\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAny ICH\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e28/64(43.8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e121/453(26.7)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.47(0.274\u0026ndash;0.801)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.01\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e0.49(0.23\u0026ndash;1.04)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e \u003cp\u003e0.06\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSymptomatic ICH \u0026Dagger;\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e10/64(15.6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e41/449(9.1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.65(0.26\u0026ndash;1.15)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.11\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e0.38(0.14\u0026ndash;1.05)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e \u003cp\u003e0.06\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003ctfoot\u003e \u003ctr\u003e\u003ctd colspan=\"7\"\u003eIQR, interquartile range; PRT, puncture-reperfusion time; mRS, modified Rankin Scale.\u003c/td\u003e\u003c/tr\u003e \u003ctr\u003e\u003ctd colspan=\"7\"\u003e\u0026Dagger; Symptomatic ICH indicates symptomatic intracranial hemorrhage which is assessed according to the Heidelberg bleeding classification criteria.\u003c/td\u003e\u003c/tr\u003e \u003c/tfoot\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec8\" class=\"Section2\"\u003e \u003ch2\u003eSubgroups analysis\u003c/h2\u003e \u003cp\u003eWe also modeled the relationship between onset-to-reperfusion time and rate of favorable functional outcome to further screen subgroups which exhibited heightened sensitivity to reperfusion timing (Supplementary Fig.\u0026nbsp;1). 252 minutes was determined as the onset-to-reperfusion time cutoff. The process of screening subgroups was presented in supplementary table \u003cspan refid=\"MOESM1\" class=\"InternalRef\"\u003e1\u003c/span\u003e and supplementary table 2. After onset-to-reperfusion time was dichotomized at 252 minutes, subgroups of younger age (\u0026lt;\u0026thinsp;65 years; aOR 0.42, 95% CI [0.19\u0026ndash;0.92], P\u0026thinsp;=\u0026thinsp;0.03), those receiving intravenous thrombolysis (aOR 0.41, 95% CI [0.17-1.00], P\u0026thinsp;=\u0026thinsp;0.05), and those with higher baseline ASPECTS (\u0026ge;\u0026thinsp;8; aOR 0.58, 95% CI [0.35\u0026ndash;0.96], P\u0026thinsp;=\u0026thinsp;0.03) tended to have a higher rate of obtaining favorable functional outcome. No significant difference was noted after the puncture-to-reperfusion time was dichotomized at 51 minutes. There was no heterogeneity in the effect of prolonged onset-to-reperfusion time and puncture-to-reperfusion time on favorable functional outcomes across age, intravenous thrombolysis, baseline NIHSS or ASPECT score, presence of tandem lesions, type of anesthesia, and successful reperfusion.\u003c/p\u003e \u003cp\u003e \u003cb\u003eKey subgroups comparison of outcomes between patients achieved successful reperfusion with prolonged PRT and those achieved partial reperfusion\u003c/b\u003e \u003c/p\u003e \u003cp\u003eKey subgroups comparison of the primary, secondary and safety outcomes between patients achieving successful reperfusion with prolonged PRT and those with partial reperfusion irrespective of procedural duration was presented in Table \u003cspan refid=\"Tab3\" class=\"InternalRef\"\u003e3\u003c/span\u003e. In the age\u0026thinsp;\u0026lt;\u0026thinsp;65 subgroup, patients achieving successful reperfusion with prolonged PRT had a higher rate of obtaining mRS 0\u0026ndash;3 (aOR 5.03, 95% CI [1.16\u0026ndash;21.83], P\u0026thinsp;=\u0026thinsp;0.03), while no significant differences were observed in rates of primary outcome (mRS at 90 days; aOR 0.41 [95% CI 0.10\u0026ndash;1.59], P\u0026thinsp;=\u0026thinsp;0.20), mRS 0\u0026ndash;1(aOR 2.09 [95% CI 0.46\u0026ndash;9.57], P\u0026thinsp;=\u0026thinsp;0.34), mRS 0\u0026ndash;2(aOR 2.56 [95% CI 0.56\u0026ndash;11.57], P\u0026thinsp;=\u0026thinsp;0.22) and safety outcomes(mortality: aOR 0.51, 95% CI 0.10\u0026ndash;2.69; P\u0026thinsp;=\u0026thinsp;0.43; ICH: aOR 0.31, 95% CI [0.08\u0026ndash;1.28], P\u0026thinsp;=\u0026thinsp;0.11; sICH: aOR 0.37, 95% CI 0.07\u0026ndash;2.02; P\u0026thinsp;=\u0026thinsp;0.25). In the intravenous thrombolysis subgroup, significantly lower rates of any intracranial hemorrhage and symptomatic hemorrhage were observed in patients achieving successful reperfusion with prolonged PRT (aOR 0.13, 95% CI [0.02\u0026ndash;0.73], P\u0026thinsp;=\u0026thinsp;0.02; aOR 0.13, 95% CI [0.02\u0026ndash;0.76], P\u0026thinsp;=\u0026thinsp;0.02 respectively), whereas no differences were observed in primary outcome (mRS at 90 days; aOR 0.73 [95% CI 0.16\u0026ndash;3.23], P\u0026thinsp;=\u0026thinsp;0.67), secondary outcomes (mRS 0\u0026ndash;1: aOR 1.34 [95% CI 0.21\u0026ndash;8.62], P\u0026thinsp;=\u0026thinsp;0.76; mRS 0\u0026ndash;2: aOR 1.70 [95% CI 0.26\u0026ndash;10.93], P\u0026thinsp;=\u0026thinsp;0.58; mRS 0\u0026ndash;3: aOR 2.67 [95% CI 0.40-17.68], P\u0026thinsp;=\u0026thinsp;0.31) and mortality (aOR 0.14 [95% CI 0.01\u0026ndash;2.47] P\u0026thinsp;=\u0026thinsp;0.18). In the ASPECTS\u0026thinsp;\u0026ge;\u0026thinsp;8 Subgroup, All outcomes were comparable between groups.\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab3\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 3\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eOutcomes of subgroups between patients achieving successful reperfusion with prolonged puncture-to-reperfusion time and partial reperfusion.\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"7\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c6\" colnum=\"6\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c7\" colnum=\"7\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colname=\"c2\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003ePartial reperfusion\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003eSuccessful reperfusion and PRT\u0026thinsp;\u0026ge;\u0026thinsp;51\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colspan=\"2\" nameend=\"c5\" namest=\"c4\"\u003e \u003cp\u003eUnadjusted analysis\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colspan=\"2\" nameend=\"c7\" namest=\"c6\"\u003e \u003cp\u003eAdjusted analysis\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003eOR (95% CI)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c5\"\u003e \u003cp\u003eP value\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c6\"\u003e \u003cp\u003eOR* (95% CI)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c7\"\u003e \u003cp\u003eP value\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAge\u0026lt;65 subgroup\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003emRS at 90 d, median (IQR)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e4(3\u0026ndash;5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1(0\u0026ndash;4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.27(0.11\u0026ndash;0.66)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.01\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e0.41(0.10\u0026ndash;1.59)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e \u003cp\u003e0.20\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003emRS 0\u0026ndash;1 at 90 d\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e6/25(24.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e135/257(52.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e3.50(1.36\u0026ndash;9.06)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.01\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e2.09(0.46\u0026ndash;9.57)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e \u003cp\u003e0.34\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003emRS 0\u0026ndash;2 at 90 d\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e6/25(24.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e149/257(58.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e4.37(1.69\u0026ndash;11.30)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.01\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e2.56(0.56\u0026ndash;11.57)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e \u003cp\u003e0.22\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003emRS 0\u0026ndash;3 at 90 d\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e11/25(44.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e182/257(70.8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e3.09(1.34\u0026ndash;7.11)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.01\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e5.03(1.16\u0026ndash;21.83)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e \u003cp\u003e0.03\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eDeath within 90 d\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e5/25(20.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e28/257(10.9)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.49(0.17\u0026ndash;1.41)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.18\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e0.51(0.10\u0026ndash;2.69)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e \u003cp\u003e0.43\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAny ICH\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e12/26(46.2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e55/252(21.8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.33(0.14\u0026ndash;0.75)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.01\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e0.31(0.08\u0026ndash;1.28)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e \u003cp\u003e0.11\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSymptomatic ICH \u0026Dagger;\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e4/26(15.4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e20/252(7.9)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.47(0.15\u0026ndash;1.51)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.21\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e0.37(0.07\u0026ndash;2.02)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e \u003cp\u003e0.25\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eIntravenous thrombolysis subgroup\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003emRS at 90 d, median (IQR)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e4(1\u0026ndash;4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e3(0\u0026ndash;4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.63(0.22\u0026ndash;1.84)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.40\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e0.73(0.16\u0026ndash;3.23)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e \u003cp\u003e0.67\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003emRS 0\u0026ndash;1 at 90 d\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e6/18(33.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e97/220(44.1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e1.58(0.57\u0026ndash;4.35)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.38\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e1.34(0.21\u0026ndash;8.62)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e \u003cp\u003e0.76\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003emRS 0\u0026ndash;2 at 90 d\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e6/18(33.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e103/220(46.8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e1.76(0.64\u0026ndash;4.86)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.27\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e1.70(0.26\u0026ndash;10.93)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e \u003cp\u003e0.58\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003emRS 0\u0026ndash;3 at 90 d\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e7/18(38.9)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e129/220(58.6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e2.23(0.83\u0026ndash;5.96)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.11\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e2.67(0.40-17.68)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e \u003cp\u003e0.31\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eDeath within 90 d\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e2/18(11.1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e30/220(13.6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e1.26(0.28\u0026ndash;5.77)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.76\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e0.14(0.01\u0026ndash;2.47)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e \u003cp\u003e0.18\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAny ICH\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e10/20(50.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e57/216(26.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.35(0.14\u0026ndash;0.89)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.03\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e0.13(0.02\u0026ndash;0.73)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e \u003cp\u003e0.02\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSymptomatic ICH \u0026Dagger;\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e5/20(25.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e19/217(8.8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.29(0.09\u0026ndash;0.88)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.03\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e0.13(0.02\u0026ndash;0.76)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e \u003cp\u003e0.02\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eASPECTS\u0026thinsp;\u0026ge;\u0026thinsp;8 subgroup\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003emRS at 90 d, median (IQR)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e4(1\u0026ndash;5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e3(0\u0026ndash;5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.44(0.21\u0026ndash;0.91)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.03\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e0.88(0.32\u0026ndash;2.42)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e \u003cp\u003e0.81\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003emRS 0\u0026ndash;1 at 90 d\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e12/41(29.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e193/427(45.2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e1.99(0.99\u0026ndash;4.01)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.05\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e1.08(0.34\u0026ndash;3.42)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e \u003cp\u003e0.90\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003emRS 0\u0026ndash;2 at 90 d\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e14/41(34.2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e208/427(48.7)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e1.83(0.94\u0026ndash;3.59)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.08\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e1.12(0.36\u0026ndash;3.44)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e \u003cp\u003e0.84\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003emRS 0\u0026ndash;3 at 90 d\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e18/41(43.9)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e250/427(58.6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e1.81(0.95\u0026ndash;3.44)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.07\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e1.74(0.56\u0026ndash;5.43)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e \u003cp\u003e0.34\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eDeath within 90 d\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e10/41(24.4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e67/427(15.7)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.58(0.27\u0026ndash;1.23)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.16\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e1.29(0.22\u0026ndash;7.45)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e \u003cp\u003e0.78\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAny ICH\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e15/44(34.1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e102/423(24.1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.61(0.32\u0026ndash;1.19)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.15\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e0.97(0.34\u0026ndash;2.80)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e \u003cp\u003e0.96\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSymptomatic ICH \u0026Dagger;\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e3/44(6.8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e36/418(8.6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e1.29(0.38\u0026ndash;4.37)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.68\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e0.66(0.14\u0026ndash;3.04)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e \u003cp\u003e0.59\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003ctfoot\u003e \u003ctr\u003e\u003ctd colspan=\"7\"\u003eIQR, interquartile range; PRT, puncture-reperfusion time; mRS, modified Rankin Scale.\u003c/td\u003e\u003c/tr\u003e \u003ctr\u003e\u003ctd colspan=\"7\"\u003e\u0026Dagger; Symptomatic ICH indicates symptomatic intracranial hemorrhage which is assessed according to the Heidelberg bleeding classification criteria.\u003c/td\u003e\u003c/tr\u003e \u003c/tfoot\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003c/div\u003e"},{"header":"Discussion","content":"\u003cp\u003eOur study suggests that PRT as an easily accessible variable, could be a crucial indicator for procedural termination. Extending procedural duration beyond the 51-minute PRT threshold may yield clinical benefits, particularly in younger patients, while limited efficacy were indicated in intravenous thrombolysis-treated patients and baseline ASPECTS\u0026thinsp;\u0026ge;\u0026thinsp;8 patients. We believe this is a crucial exploration as this individualized termination protocols can directly impact the clinical decision-making process in the field of acute ischemic stroke due to LVO.\u003c/p\u003e \u003cp\u003eAside from PRT, the optimal number of thrombectomy attempts has been extensively investigated as a key determinant of EVT efficacy. In the process of our clinical practice, when successful reperfusion is hard to achieve, the number of thrombectomy attempt could be a key factor to be taken into account based on current evidence. Contemporary evidence suggests diminishing clinical outcomes when exceeding three retrieval attempts for ischemic stroke due to anterior LVO\u003csup\u003e\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e,\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e,\u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e\u003c/sup\u003e, a threshold balancing successful reperfusion against procedural risks as repeated thrombectomy induce blood-brain barrier disruption, elevating intracranial hemorrhage risk, while simultaneously reducing recanalization probabilities due to refractory thrombi and distal embolization\u003csup\u003e\u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e\u003c/sup\u003e. However, retrieval attempt limits may not suit all clinical contexts, bailout angioplasty - including balloon dilation and stent implantation \u0026ndash; is needed in atherosclerosis lesion, adjunctive techniques are also needed for tortuous access to the occlusion site, such standard undermines the necessity for operator flexibility in complex cases. Moreover, there are studies suggest that the establishment of arbitrary thrombectomy pass count thresholds may lead to early termination of EVT\u003csup\u003e\u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e\u003c/sup\u003e.\u003c/p\u003e \u003cp\u003eOur findings demonstrate a nonlinear relationship between PRT and functional independence (mRS 0\u0026ndash;2). Beyond the 51-minute threshold, a transient increase in favorable outcomes is observed. However, this benefit diminishes with time elapsing. This underscores the necessity for individualized protocols. Jia et al suggested that in patients with failed thrombectomy attributable to non-mechanical factors (e.g., access challenges or refractory thrombus), prolonging procedural duration to implement strategies to access occlusion site may confer enhanced clinical benefits in functional recovery\u003csup\u003e\u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e\u003c/sup\u003e. However, this benefit doesn\u0026rsquo;t exist persistently. There is evidence indicates that PRT exceeding 60 minutes yields diminishing benefits, regardless of thrombectomy attempts\u003csup\u003e\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e\u003c/sup\u003e. This phenomenon implies that prolonged time spent on recanalization \u0026ndash; even when followed by successful recanalization \u0026ndash; may negate therapeutic benefits.\u003c/p\u003e \u003cp\u003eIn our study, subgroup analysis of onset-to-reperfusion time revealed distinct time-sensitivity across patient subgroups: patients with younger age, higher ASPECTS, and the administration of intravenous thrombolysis are less likely to achieve a favorable functional outcome as the time to reperfusion increases. Notably, this time-sensitivity was absent when analyzing PRT across all subgroups. This finding may be explained by the fact that onset-to-reperfusion time encapsulates total ischemic duration from symptom onset, directly correlating with neuronal salvage potential, while PRT isolates procedural duration, a small portion of onset-to-puncture time. Thus, the time-sensitive nature is more prominent in onset-to-reperfusion time rather than PRT. Several factors may explain why these populations are more sensitive to time to reperfusion. In younger patients, less atherosclerosis and a higher likelihood of cardiogenic thrombus are common\u003csup\u003e\u003cspan citationid=\"CR24\" class=\"CitationRef\"\u003e24\u003c/span\u003e\u003c/sup\u003e, where limited collaterals accelerate infarct growth. In patients receiving intravenous thrombolysis, early recanalization creates larger penumbra\u003csup\u003e\u003cspan citationid=\"CR25\" class=\"CitationRef\"\u003e25\u003c/span\u003e,\u003cspan citationid=\"CR26\" class=\"CitationRef\"\u003e26\u003c/span\u003e\u003c/sup\u003e, heightening vulnerability to delayed successful reperfusion. Patients with higher ASPECTS (\u0026ge;\u0026thinsp;8) also have larger penumbra.\u003c/p\u003e \u003cp\u003eNotably, in the intravenous thrombolysis subgroup, patients achieving partial reperfusion demonstrated significantly higher rates of ICH and sICH, this can be explained from the following aspects: (1) partial reperfusion patients is associated with larger final infarct core volumes compared to those achieved successful reperfusion\u003csup\u003e\u003cspan citationid=\"CR27\" class=\"CitationRef\"\u003e27\u003c/span\u003e,\u003cspan citationid=\"CR28\" class=\"CitationRef\"\u003e28\u003c/span\u003e\u003c/sup\u003e. (2) Thrombolytic-induced clot disruption and distal embolization of fragments necessitate increased thrombectomy attempts, a process that induces endothelial damage and consequently elevates hemorrhagic risk\u003csup\u003e\u003cspan citationid=\"CR29\" class=\"CitationRef\"\u003e29\u003c/span\u003e,\u003cspan citationid=\"CR30\" class=\"CitationRef\"\u003e30\u003c/span\u003e\u003c/sup\u003e. This phenomenon underscores the need for early procedural termination decisions in bridging therapy patients when complete recanalization proves challenging.\u003c/p\u003e \u003cp\u003eThis study is the first to establish a 51-minute puncture-to-reperfusion time (PRT) threshold using restricted cubic spline analysis in a multicenter cohort. Contrary to the prevailing \"the sooner, the better\" doctrine, our data reveal a transient therapeutic window where persistent recanalization attempts improve favorable functional outcome rate in challenging cases. This challenges the universality of fixed time cutoffs in clinical practice. Through subgroup analysis, we also identified potential populations who may and may not benefit from extended procedural duration. Moreover, using PRT threshold to guide procedural termination decision underscores operator flexibility in challenging cases.\u003c/p\u003e \u003cp\u003eThe limitations of our study are as follows. First, the retrospective analysis of the ANGEL-ACT registry introduces potential selection bias. Second, key prognostic variables, including detailed collateral circulation status (e.g., ASITN/SIR scores) and thrombus composition analysis, were not systematically collected. Third, the limited sample size in subgroup comparison prompts the interpretation of the results should be cautious. Forth, all participants of ANGEL-ACT registry are Chinese, the high percentage of ICAD in the Chinese population may confound the conclusions and may not be applied to other populations.\u003c/p\u003e"},{"header":"Conclusion","content":"\u003cp\u003ePatients could benefit from successful reperfusion when PRT exceeds 51 minutes, particularly for younger patients (\u0026lt;65 years), while patients received intravenous thrombolysis and patients with ASPECTS\u0026ge;8 may not. Individualized termination protocols are needed, further validation is warranted prior to clinical implementation.\u003c/p\u003e\n"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eAcknowledgements\u0026nbsp;\u003c/strong\u003eWe thank all participating hospitals, relevant clinicians, statisticians, and imaging and laboratory technicians.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAuthor Contributions\u0026nbsp;\u003c/strong\u003eZM designed, led the study and had full access to all of the data in the study and took responsibility for the integrity of the data and the accuracy of the data analysis. ZY and FC prepared the first draft of the report, WL made revisions of draft. All authors critically reviewed the report and approved the final version. All authors critically reviewed the report and approved the final version.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAdditional Information\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eDisclosures\u0026nbsp;\u003c/strong\u003eNone.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFunding\u0026nbsp;\u003c/strong\u003eThis study is supported by National Key Research and Development Program of China (2016 YFC1301500).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eEthical approval\u0026nbsp;\u003c/strong\u003eAll procedures performed in studies involving human participants were in accordance with the 1964 Helsinki declaration and its later amendments or comparable ethical standards. The protocol and data collection were approved by the ethics committees of Beijing Tiantan Hospital and each participating site. Each participant or his/her legal representative gave written informed consent before being enrolled in the study. This article does not contain any studies with animals performed by any of the authors.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConsent to Participate\u003c/strong\u003e Individual patients\u0026rsquo; written informed consent was waived owing to the retrospective nature of the study.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConflict of interest\u003c/strong\u003e The authors declare no competing interests.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eData availability statement\u0026nbsp;\u003c/strong\u003eAnonymized data not published in this article are available from the corresponding author on reasonable request.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\n\u003cli\u003eBerkhemer, O. 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L.\u003cem\u003e et al.\u003c/em\u003e Time to Treatment With Endovascular Thrombectomy and Outcomes From Ischemic Stroke: A Meta-analysis. \u003cem\u003eJama\u003c/em\u003e \u003cstrong\u003e316\u003c/strong\u003e https://doi.org/10.1001/jama.2016.13647 (2016).\u003c/li\u003e\n\u003cli\u003eFlottmann, F.\u003cem\u003e et al.\u003c/em\u003e Recanalization Rate per Retrieval Attempt in Mechanical Thrombectomy for Acute Ischemic Stroke. \u003cem\u003eStroke\u003c/em\u003e \u003cstrong\u003e49\u003c/strong\u003e, 2523-2525 https://doi.org/10.1161/strokeaha.118.022737 (2018).\u003c/li\u003e\n\u003cli\u003eGarc\u0026iacute;a-Tornel, \u0026Aacute;.\u003cem\u003e et al.\u003c/em\u003e When to Stop. \u003cem\u003eStroke\u003c/em\u003e \u003cstrong\u003e50\u003c/strong\u003e, 1781-1788 https://doi.org/10.1161/strokeaha.119.025088 (2019).\u003c/li\u003e\n\u003cli\u003eSeker, F.\u003cem\u003e et al.\u003c/em\u003e Correlation of Thrombectomy Maneuver Count with Recanalization Success and Clinical Outcome in Patients with Ischemic Stroke. \u003cem\u003eAmerican Journal of Neuroradiology\u003c/em\u003e \u003cstrong\u003e38\u003c/strong\u003e, 1368-1371 https://doi.org/10.3174/ajnr.A5212 (2017).\u003c/li\u003e\n\u003cli\u003eJia, B.\u003cem\u003e et al.\u003c/em\u003e Current Status of Endovascular Treatment for Acute Large Vessel Occlusion in China. \u003cem\u003eStroke\u003c/em\u003e \u003cstrong\u003e52\u003c/strong\u003e, 1203-1212 https://doi.org/10.1161/strokeaha.120.031869 (2021).\u003c/li\u003e\n\u003cli\u003evon Kummer, R.\u003cem\u003e et al.\u003c/em\u003e The Heidelberg Bleeding Classification. \u003cem\u003eStroke\u003c/em\u003e \u003cstrong\u003e46\u003c/strong\u003e, 2981-2986 https://doi.org/10.1161/strokeaha.115.010049 (2015).\u003c/li\u003e\n\u003cli\u003eFlottmann, F.\u003cem\u003e et al.\u003c/em\u003e Good Clinical Outcome Decreases With Number of Retrieval Attempts in Stroke Thrombectomy. \u003cem\u003eStroke\u003c/em\u003e \u003cstrong\u003e52\u003c/strong\u003e, 482-490 https://doi.org/10.1161/strokeaha.120.029830 (2021).\u003c/li\u003e\n\u003cli\u003eFilioglo, A.\u003cem\u003e et al.\u003c/em\u003e More than five stentriever passes: real benefit or futile recanalization? \u003cem\u003eNeuroradiology\u003c/em\u003e \u003cstrong\u003e62\u003c/strong\u003e, 1335-1340 https://doi.org/10.1007/s00234-020-02469-x (2020).\u003c/li\u003e\n\u003cli\u003eLuby, M.\u003cem\u003e et al.\u003c/em\u003e Frequency of Blood-Brain Barrier Disruption Post-Endovascular Therapy and Multiple Thrombectomy Passes in Acute Ischemic Stroke Patients. \u003cem\u003eStroke\u003c/em\u003e \u003cstrong\u003e50\u003c/strong\u003e, 2241-2244 https://doi.org/10.1161/strokeaha.119.025914 (2019).\u003c/li\u003e\n\u003cli\u003eMohammaden, M. H.\u003cem\u003e et al.\u003c/em\u003e Lack of Reperfusion Rather Than Number of Passes Defines Futility in Stroke Thrombectomy: A Matched Case-Control Study. \u003cem\u003eStroke\u003c/em\u003e \u003cstrong\u003e52\u003c/strong\u003e, 2757-2763 https://doi.org/10.1161/strokeaha.120.033539 (2021).\u003c/li\u003e\n\u003cli\u003eJia, B.\u003cem\u003e et al.\u003c/em\u003e Rescue angioplasty and/or stenting after mechanical thrombectomy: who can benefit? \u003cem\u003eJournal of NeuroInterventional Surgery\u003c/em\u003e \u003cstrong\u003e16\u003c/strong\u003e, 1360-1367 https://doi.org/10.1136/jnis-2023-020824 (2024).\u003c/li\u003e\n\u003cli\u003ePerera, K. S.\u003cem\u003e et al.\u003c/em\u003e Evaluating Rates of Recurrent Ischemic Stroke Among Young Adults With Embolic Stroke of Undetermined Source. \u003cem\u003eJAMA Neurology\u003c/em\u003e \u003cstrong\u003e79\u003c/strong\u003e https://doi.org/10.1001/jamaneurol.2022.0048 (2022).\u003c/li\u003e\n\u003cli\u003eMajoie, C. B.\u003cem\u003e et al.\u003c/em\u003e Value of intravenous thrombolysis in endovascular treatment for large-vessel anterior circulation stroke: individual participant data meta-analysis of six randomised trials. \u003cem\u003eThe Lancet\u003c/em\u003e \u003cstrong\u003e402\u003c/strong\u003e, 965-974 https://doi.org/10.1016/s0140-6736(23)01142-x (2023).\u003c/li\u003e\n\u003cli\u003eSeners, P.\u003cem\u003e et al.\u003c/em\u003e Arterial Recanalization During Interhospital Transfer for Thrombectomy. \u003cem\u003eStroke\u003c/em\u003e \u003cstrong\u003e55\u003c/strong\u003e, 1525-1534 https://doi.org/10.1161/strokeaha.124.046694 (2024).\u003c/li\u003e\n\u003cli\u003eCappellari, M.\u003cem\u003e et al.\u003c/em\u003e IER-SICH Nomogram to Predict Symptomatic Intracerebral Hemorrhage After Thrombectomy for Stroke. \u003cem\u003eStroke\u003c/em\u003e \u003cstrong\u003e50\u003c/strong\u003e, 909-916 https://doi.org/10.1161/strokeaha.118.023316 (2019).\u003c/li\u003e\n\u003cli\u003evan der Steen, W.\u003cem\u003e et al.\u003c/em\u003e Determinants of Symptomatic Intracranial Hemorrhage After Endovascular Stroke Treatment: A Retrospective Cohort Study. \u003cem\u003eStroke\u003c/em\u003e \u003cstrong\u003e53\u003c/strong\u003e, 2818-2827 https://doi.org/10.1161/strokeaha.121.036195 (2022).\u003c/li\u003e\n\u003cli\u003eTong, X.\u003cem\u003e et al.\u003c/em\u003e Thrombectomy Versus Combined Thrombolysis and Thrombectomy in Patients With Acute Stroke. \u003cem\u003eStroke\u003c/em\u003e \u003cstrong\u003e52\u003c/strong\u003e, 1589-1600 https://doi.org/10.1161/strokeaha.120.031599 (2021).\u003c/li\u003e\n\u003cli\u003eRen, Y.\u003cem\u003e et al.\u003c/em\u003e Clot Migration Is Associated With Intravenous Thrombolysis in the Setting of Acute Ischemic Stroke. \u003cem\u003eStroke\u003c/em\u003e \u003cstrong\u003e49\u003c/strong\u003e, 3060-3062 https://doi.org/10.1161/strokeaha.118.022751 (2018).\u003c/li\u003e\n\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":true,"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":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true},"keywords":"thrombectomy, puncture-to-reperfusion time, mRS, RCS","lastPublishedDoi":"10.21203/rs.3.rs-6332896/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-6332896/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003ch2\u003ePurpose\u003c/h2\u003e \u003cp\u003eThe role of puncture-to-reperfusion time (PRT) remains under investigation. Our study aimed to explore whether it could serve as an indicator for procedural termination.\u003c/p\u003e\u003ch2\u003eMethods\u003c/h2\u003e \u003cp\u003ePatients who underwent endovascular therapy within 6 hours of onset due to anterior large-vessel occlusion were selected from ANGEL-ACT. Restricted cubic splines (RCS) with 3 knots defined PRT thresholds. Outcomes were compared successful reperfusion with prolonged PRT (PRT\u0026thinsp;\u0026gt;\u0026thinsp;51 min) and partial reperfusion groups. Potential subgroups who might benefit from prolonged PRT were compared. Primary outcome was 90-day mRS, safety outcomes were mortality at 90days, any intracranial hemorrhage and symptomatic intracranial hemorrhage.\u003c/p\u003e\u003ch2\u003eResults\u003c/h2\u003e \u003cp\u003e51 minutes was determined as PRT cutoff in our study. Those achieved successful reperfusion with prolonged PRT had higher mRS 0\u0026ndash;3 rate compared with those achieved partial reperfusion (aOR 2.86 [95% CI 1.21\u0026ndash;6.76], P\u0026thinsp;=\u0026thinsp;0.02); No significant differences were found in other outcomes. Subgroup analysis indicated similar result in patients aged\u0026thinsp;\u0026lt;\u0026thinsp;65 years, while no significant difference in primary outcome was observed in intravenous thrombolysis subgroup and ASPECTS\u0026thinsp;\u0026ge;\u0026thinsp;8 subgroup.\u003c/p\u003e\u003ch2\u003eConclusion\u003c/h2\u003e \u003cp\u003eOur findings suggest that prolonged PRT improves outcomes, particularly in patients\u0026thinsp;\u0026lt;\u0026thinsp;65 years, but not in patients received intravenous thrombolysis or ASPECTS\u0026thinsp;\u0026ge;\u0026thinsp;8. Individualized termination protocols are needed, pending further validation.\u003c/p\u003e","manuscriptTitle":"Puncture-to-Reperfusion Time Threshold Guides Procedural Termination in Thrombectomy: Analysis from the ANGEL-ACT Registry","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2025-05-13 06:47:37","doi":"10.21203/rs.3.rs-6332896/v1","editorialEvents":[{"type":"communityComments","content":1}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"70b3857b-8369-4e11-a5d9-0a582ce02b52","owner":[],"postedDate":"May 13th, 2025","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[{"id":48277672,"name":"Biological sciences/Neuroscience/Diseases of the nervous system/Stroke"},{"id":48277673,"name":"Health sciences/Neurology/Neurological disorders/Cerebrovascular disorders/Stroke"}],"tags":[],"updatedAt":"2025-06-16T11:08:49+00:00","versionOfRecord":[],"versionCreatedAt":"2025-05-13 06:47:37","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-6332896","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-6332896","identity":"rs-6332896","version":["v1"]},"buildId":"8U1c8b4HqxoKbykW_rLl7","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}