Bridging Thrombolysis Does Not Achieve Better Outcomes Compared to Direct Mechanical Thrombectomy in Stroke Due to Internal Carotid Artery Occlusion

Bridging Thrombolysis Does Not Achieve Better Outcomes Compared to Direct Mechanical Thrombectomy in Stroke Due to Internal Carotid Artery Occlusion | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Research Article Bridging Thrombolysis Does Not Achieve Better Outcomes Compared to Direct Mechanical Thrombectomy in Stroke Due to Internal Carotid Artery Occlusion Isabel Siow, Keng Siang Lee, Benjamin YQ Tan, Dominic WT Yap, and 24 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-7901947/v1 This work is licensed under a CC BY 4.0 License Status: Published Journal Publication published 21 Jan, 2026 Read the published version in Neuroradiology → Version 1 posted You are reading this latest preprint version Abstract Background and purpose. Mechanical thrombectomy (MT) is an effective treatment for patients with acute ischaemic stroke secondary to internal carotid artery (ICA) occlusion. Intravenous thrombolysis (IVT) prior to MT is also commonly administered in suitable patients. This study aimed to compare the outcomes of patients with acute ICA stroke who were treated with direct MT versus combined IVT plus MT. Additionally, analysis was performed in different subgroups of patients such as those with large artery stenosis (LAA) to evaluate which subgroup of patients would benefit most from bridging IVT. Methods. This multicenter retrospective cohort study included patients who were treated for acute ICA stroke from three comprehensive stroke centers between January 2015 and December 2019. Patients received direct MT or combined bridging IVT plus MT. Primary outcome was favorable functional outcome defined as modified Rankin Scale (mRS) 0–2 measured at 90 days after discharge. Secondary outcome measures included mRS on discharge, inpatient mortality and complications such as symptomatic intracranial hemorrhage (sICH), subarachnoid haemorrhage (SAH) and embolism of thrombus to new territories. Results. Among 352 patients, 178 (50.6%) patients underwent bridging IVT followed by MT and 174 (49.4%) underwent direct MT. The mean ± standard deviation age was 69.8 ± 14.6 years, 50.9% were male and median National Institutes of Health Stroke Scale was 16 (interquartile range). At 90-days after discharge, patients who underwent bridging IVT had similar functional outcomes as those who underwent direct MT (33.5% vs 27.7%, P = 0.255). On multivariable analyses, bridging IVT was not associated with improvement in discharge mRS score, 90-day mRS score, decreased mortality or difference in rate of complications compared to direct MT. In subgroup analyses, patients with underlying atherosclerosis treated with bridging IVT compared to direct MT had a higher rate of favorable functional outcome at 90 days (33.9% vs. 14.0%, P = 0.022) Conclusions. Bridging IVT is not associated with better functional outcomes compared to direct MT in ICA stroke. However, in the subgroup of patients with underlying large-artery atherosclerosis stroke mechanism, bridging IVT appears to potentially confer beneficial outcomes. This should be validated in larger studies. Introduction Internal carotid artery (ICA) occlusion affects approximately 15% of patients with acute ischaemic stroke secondary to large vessel occlusion. 1 Without treatment, it frequently leads to adverse outcomes, causing significant rates of morbidity and mortality. In patients who present within the time window, the standard of care for ICA occlusion is mechanical thrombectomy (MT). 2 Administration of bridging intravenous thrombolysis (IVT) prior to MT is also commonly recommended in patients with no contraindications. 3 The main aim of IVT is to assist in achieving recanalisation of the culprit vessel. 4 Additionally, if MT succeeds, bridging IVT can potentially assist in dissolution of distal emboli that might have been dislodged during the MT procedure. However, bridging IVT is not without risks. 4 Intracranial haemorrhage and gastrointestinal bleeding can result in severe adverse outcomes. 5 Several recent large-scale studies on the efficacy of bridging IVT prior to MT have revealed conflicting results. Some studies report equivalent effects achieved in bridging IVT and direct MT 6 while others report superior functional outcomes in patients with bridging IVT. 6 , 7 As such, an optimal clinical management protocol in patients with ICA occlusion has yet to be established. We therefore performed a multi-centre retrospective cohort study conducted across 3 large comprehensive stroke centres across Europe to determine whether bridging IVT as opposed to direct MT alone would be beneficial in patients with ICA occlusion acute ischaemic stroke. Methods Ethics and standard protocol approvals This retrospective cohort study was approved by the National University Health System Institutional Review Board (ID: DSRB 2019/00252). A waiver of individual participant consent was granted. Patients and treatment Consecutive patients from three comprehensive stroke centers across Europe with ICA occlusion acute ischaemic stroke who underwent MT between January 2015 and December 2019 were included. Of these, patients with a premorbid modified Rankin Scale (mRS) ≥ 2 were excluded from this study. 8 Prior to MT, all patients underwent baseline neurovascular imaging with computed tomography (CT) and CT angiography. Patients were considered for bridging thrombolysis if they presented within 4.5 hours of symptom onset, if they had no contraindications, and administration was at the final discretion of the treating stroke neurologist. 9 In each institution, IVT was administered by an accredited neurologist at a dose of 0.9 mg/kg. 8 At all centers, patients were considered eligible for MT if the procedure could be initiated within 24 hours of the time of stroke onset and had an angiographically confirmed occlusion in the internal carotid artery. Patients with tandem lesions were included in the study. Patients were excluded from thrombectomy when pre-treatment imaging revealed extensive ischemic changes, or if the stroke was considered mild based on an admission National Institutes of Health Stroke Scale (NIHSS) score of 3 or less. 9 Clinical monitoring was performed in either the intensive care unit or high dependency unit setting during the initial acute episode. 10 All patients were managed according to international guidelines for the management of AIS. 10 Participating stroke centers employed either a stent-retriever, direct aspiration catheter, or combined stent-retriever and aspiration via intermediate catheter approach from the start of the procedure, this was at the discretion of the interventionist. Follow-up CT scan was performed at around 24 hours after initial treatment. 11 Data collection The following epidemiological information was extracted from patient records: age, sex, race, and smoking history. Comorbidities studied included hypertension, hyperlipidaemia, diabetes mellitus, atrial fibrillation, and previous ischemic stroke. These conditions were defined based on guidelines by the World Health Organization 12 and American Heart Association 13 – 15 . The mechanism of ischemic stroke was defined according to the Trial of ORG 10172 in Acute Stroke Treatment (TOAST) classification, 16 NIHSS score 17 on admission and the time from stroke onset to groin puncture were extracted. Primary and secondary outcomes The primary outcome measure was a favorable functional outcome defined by mRS ≤ 2 after 90 days. Secondary measures of outcome were in-hospital mortality, good functional outcome defined as mRS ≤ 2 at discharge, and rates of complications such as spontaneous intracranial hemorrhage (sICH), subarachnoid hemorrhage (SAH) and embolisation to new territories. Other secondary measures of outcome were favourable functional outcome as defined by mRS ≤ 3 after 90 days and mRS ≤ 3 at discharge. Further subgroup analyses were performed to evaluate the effect of bridging IVT against direct MT in the subgroups of patients with large artery atherosclerosis (LAA), good premorbid condition (premorbid mRS 0–1), young age (≤ 75 years), advanced age (> 75 years), 18 male sex and female sex. Reperfusion was assessed using post-procedure angiography, and successful reperfusion was defined as having a 2b–3 flow as calculated using the modified Thrombolysis in Cerebral Infarction (mTICI) scale. Additionally, a subset of patients who achieved mTICI 2c and 3 grades reperfusion was also tabulated. sICH was defined by the presence of parenchymal hemorrhage with an increase in NIHSS by ≥ 4 points within 24 hours of revascularization according to the modified Safe Implementation of Thrombolysis in Stroke-Monitoring Study (SITS-MOST) criteria. 19 Any SAH present in the 24-hour post-thrombectomy CT scan was included in the definition. Statistical analysis Numeric variables were first tested for normality with the Shapiro-Wilk test. A Student’s t-test was used for normally distributed data and a Mann-Whitney U test for non-normally distributed data. Categorical variables were compared using a Pearson chi-square test, with computation of Wald and score 95% confidence interval (CI) for the incidence odds ratio (OR). Subsequently, multivariable logistic regression was carried out to identify predictors for primary and secondary outcome measures. In addition, the following exploratory subgroup analyses were performed: (1) age 75 years or younger vs. older than 75 years; (2) male vs. female sex; and (3) TOAST mechanism of large-artery atherosclerosis (LAA) vs. non-LAA strokes. P values < 0.05 were considered statistically significant. The selection of variables for multivariable analyses was decided a priori, including age, 20 sex, 21 NIHSS 22 and time from stroke onset to groin puncture. 23 These were selected based on past literature which demonstrated that they have a significant impact on functional outcomes after MT. Unknown or missing values were excluded from the denominator when calculating proportions in the study cohort. All statistical analysis was performed using SPSS version 26 (IBM Co., Armonk, NY, USA). Results Baseline characteristics A total of 352 patients were included in the study. Of these patients, 178 (50.6%) patients underwent bridging IVT prior to MT and 174 (49.4%) underwent direct MT. The baseline characteristics of the bridging IVT group and direct MT group were comparable, with similar age, race, and sex. Notably, more patients in the direct MT group had hyperlipidaemia and atrial fibrillation compared to those in the bridging IVT group. In accordance with TOAST classification, 106 patients (44.5%) had underlying LAA and 107 patients (45.0%) had stroke due to cardioembolism, 16 patients had stroke of other determined aetiology (6.7) and 9 patients had stroke of undetermined aetiology (3.8%). Stroke severity as measured by median NIHSS was similar between the two groups at a median of 16. Median time from stroke onset to groin puncture was longer in the direct MT group (median, 351.3 minutes; interquartile range [IQR], 347.9), compared to the bridging thrombolysis group (median, 256.6 minutes; IQR, 159.8; p = 0.004). Median time from groin puncture to reperfusion was similar between both groups. (Table 1 ) Table 1 Baseline characteristics of study population Characteristic Direct MT (N = 174) Bridging IVT (N = 178) Total (N = 352) p-value Age, Mean ± SD 70.3 ± 14.4 69.3 ± 14.9 69.8 ± 14.6 0.500 Sex, N (%) Male Female 91 (52.3) 83 (47.7) 88 (49.4) 90 (50.6) 179 (50.9) 173 (49.1) 0.591 Country, N (%) Germany United Kingdom Sweden 102 (58.6) 17 (9.8) 55 (31.6) 108 (60.7) 14 (7.9) 56 (31.5) 210 (59.7) 31 (8.8) 111 (31.5) 0.808 Race (all Caucasian) Hypertension, N (%) 83 (69.7) 80 (65.6) 163 (67.6) 0.489 Hyperlipidaemia, N (%) 29 (25.9) 16 (13.9) 45 (19.8) 0.024 Diabetes mellitus, N (%) 25 (21.0) 21 (17.2) 46 (19.1) 0.454 Atrial fibrillation, N (%) 60 (50.4) 39 (32.0) 99 (41.1) 0.004 Previous stroke, N (%) 14 (11.8) 7 (5.7) 21 (8.7) 0.097 Smoker 18 (16.7) 16 (14.4) 34(15.5) 0.645 TOAST classification, N (%) Large-artery atherosclerosis Cardioembolic Stroke of other determined aetiology Stroke of undetermined aetiology 45 (38.1) 61 (51.7) 8 (6.8) 4 (3.4) 61 (50.8) 46 (38.3) 8 (6.7) 5 (4.2) 106 (44.5) 107 (45.0) 16 (6.7) 9 (3.8) 0.202 Admission NIHSS, Median ± IQR 16.0 ± 7.0 17.0 ± 8.0 16.0 ± 8.0 0.153 Time from stroke onset to groin puncture 351.3 ± 347.9 256.6 ± 159.8 298.5 ± 264.2 0.004 Time from groin puncture to reperfusion 62.0 ± 128.0 66.9 ± 120.9 64.5 ± 124.3 0.725 Primary outcome Rates of favourable functional outcomes as defined by 90-day mRS 0–2 were similar between the bridging IVT group and the direct MT group (33.5% vs 27.7%, p = 0.255). (Table 2 ) After adjustment for age, sex, NIHSS and time from stroke onset to groin puncture in the multivariable model, there was still no significant difference in rates of favourable functional outcomes between the two groups (OR = 1.34; 95% CI 0.76–2.38; p = 0.317). (Table 3 ) Table 2 Comparison of outcomes between direct MT and bridging IVT groups Outcome Direct MT (N = 174) Bridging IVT (N = 178) Total (N = 352) p-value Discharge mRS, N (%) 0–2 3–6 21 (17.8) 97 (82.8) 35 (28.9) 86 (71.1) 56 (23.4) 183 (76.6) 0.042 Discharge mRS, N (%) 0–3 4–6 29 (24.6) 89 (75.4) 46 (38.0) 75 (62.0) 75 (31.4) 164 (68.4) 0.025 90-day mRS, N (%) 0–2 3–6 44 (27.7) 115 (72.3) 54 (33.5) 107 (66.5) 98 (30.6) 222 (69.4) 0.255 90-day mRS, N (%) 0–3 4–6 61 (38.4) 98 (61.6) 71 (44.1) 90 (55.9) 132 (41.3) 188 (58.8) 0.297 Inpatient mortality, N (%) 41 (23.7) 34 (19.2) 75 (21.4) 0.306 TICI post-treatment, N (%) 0-2a (poor) 2b-3 (good) 33 (19.4) 137 (80.6) 35 (20.0) 140 (80.0) 68 (19.7) 277 (80.3) 0.891 TICI post-treatment, N (%) 0-2b (poor) 2c-3 (good) 78 (45.9) 92 (54.1) 95 (54.3) 80 (45.7) 173 (50.1) 172 (49.9) 0.119 sICH, N (%) 23 (13.2) 30 (16.9) 53 (15.1) 0.340 SAH, N (%) 8 (4.6) 8 (4.5) 16 (4.5) 0.963 Embolisation to new territory, N (%) 11 (6.5) 5 (3.0) 16 (4.7) 0.130 Table 3 Comparison of outcomes between bridging IVT and direct MT groups Outcome Model 1 OR (91% CI); p-value Model 2* OR (91% CI); p-value Discharge mRS, N (%) 0–2 vs 3–6 1.88 (1.02–3.47); 0.044 1.77 (0.86–3.64); 0.123 Discharge mRS, N (%) 0–3 vs 4–6 1.88 (1.08–3.29); 0.026 2.13 (1.10–4.13); 0.025 90-day mRS, N (%) 0–2 vs 3–6 1.32 (0.82–2.13); 0.255 1.34 (0.76–2.38); 0.317 90-day mRS, N (%) 0–3 vs 4–6 1.27 (0.81–1.98); 0.298 1.293 (0.75–2.22); 0.353 Inpatient mortality, N (%) 1.31 (0.78–2.18); 0.307 1.18 (0.65–2.13); 0.587 mTICI post-treatment, N (%) 0-2a (poor) vs 2b-3 (good) 1.04 (0.61–1.77); 0.891 1.10 (0.60–2.03); 0.763 mTICI post-treatment, N (%) 0-2b (poor) vs 2c-3 (good) 1.40 (0.92–2.14); 0.119 1.42 (0.88–2.29); 0.155 sICH 0.75 (0.42–1.35); 0.341 0.62 (0.31–1.25); 0.184 SAH 1.02 (0.38–2.79); 0.963 0.56 (0.15–2.06); 0.380 Embolisation to new territory 2.26 (0.77–6.64); 0.140 2.27 (0.64–8.07); 0.207 *adjusted for age, sex, NIHSS and time from stroke onset to groin puncture Secondary outcomes Secondary outcomes were largely similar between the direct MT group and the bridging IVT group. On univariate analysis, patients in the bridging IVT group had higher rates of favourable mRS on discharge compared to those in the direct MT group (28.9% vs 17.8%, P = 0.042). (Table 2 ) However, after adjustment for age, sex, NIHSS and time from stroke onset to groin puncture in the multivariable model, bridging IVT was no longer significantly associated with favorable mRS scores on discharge (OR = 1.77; 95% CI 0.86–3.64; p-0.123). (Table 3 ) A similar proportion of patients achieved successful reperfusion (mTICI 2b–3) in the direct MT group and the bridging IVT group (80.6% and 80.0%, p = 0.891). In-hospital mortality rate was also similar between the direct MT group (23.7%) and the bridging IVT group (19.2%) (p = 0.306). Few patients sustained hemorrhagic complications, such as sICH (16.9% in the bridging IVT group vs 13.2% in the direct MT group) and SAH (4.5% in the bridging IVT group vs 4.6% in the direct MT group). Further analysis was performed with favourable functional outcomes at discharge and at 90 days defined as mRS 0–3. This was because ICA strokes and strokes with tandem lesions tend to yield worse outcomes than MCA strokes. 24 (Table 2 ) Subgroup analyses A significant treatment effect of bridging IVT was observed in the subgroup of patients who had underlying LAA (Table 4 ). In this subgroup, patients treated with bridging IVT compared to direct MT had a high rate of favorable functional outcome at discharge (37.7% vs. 18.2%, p = 0.030). Patients treated with bridging IVT still had a higher rate of favorable functional outcome at 90 days (33.9% vs 14.0%, p = 0.022). Notably, patients treated with bridging IVT had lower rates of SAH (0% vs 11.1%, p = 0.012). Rates of in-hospital mortality and rates of other complications such as sICH and embolisation of clots to new territories were comparable between the two groups. (Table 4 ) Table 4 Subgroup analysis comparing outcomes of bridging IVT vs. direct MT in internal carotid artery stroke with underlying large artery atherosclerosis (n = 105) Outcome Direct MT (N = 44) Bridging IVT (N = 61) Total (N = 105) p-value Discharge mRS, N (%) 0–2 3–6 6 (13.6) 38 (86.4) 17 (27.9) 44 (72.1) 23 (21.9) 82 (78.1) 0.082 Discharge mRS, N (%) 0–3 4–6 8 (18.2) 36 (81.8) 23 (37.7) 38 (62.3) 31 (29.5) 74 (70.5) 0.030 90-day mRS, N (%) 0–2 3–6 6 (14.0) 37 (86.0) 20 (33.9) 39 (66.1) 26 (25.5) 76 (74.5) 0.022 90-day mRS, N (%) 0–3 4–6 13 (30.2) 30 69.8) 23 (39.0) 36 (61.0) 36 (35.3) 66 (64.7) 0.361 Inpatient mortality, N (%) 15 (34.1) 18 (29.5) 33 (31.4) 0.618 TICI post-treatment, N (%) 0-2a (poor) 2b-3 (good) 12 (27.3) 32 (72.7) 14 (23.3) 46 (76.7) 26 (25.0) 78 (75.0) 0.647 TICI post-treatment, N (%) 0-2b (poor) 2c-3 (good) 28 (63.6) 16 (36.4) 35 (58.3) 25 (41.7) 63 (60.6) 41 (39.4) 0.585 sICH, N (%) 8 (17.8) 8 (13.1) 16 (15.5) 0.507 SAH, N (%) 5 (11.1) 0 (0.0) 5 (4.7) 0.012 Embolisation to new territory, N (%) 3 (6.7) 0 (0.0) 3 (2.9) 0.076 In all other subgroup analyses performed, there were no significant differences in the rates of favorable functional outcome at 90 days between the bridging IVT group and the direct MT group. Specifically, bridging IVT did not improve outcomes at 90 days in patients with good premorbid function (mRS 0–1)( IVT 38.5% vs direct MT 31.5%, p = 0.242), in the subgroup of patients who were young (age ≤ 75) (IVT 45.0% vs direct MT 32.2%, p = 0.073), in the older patients (age > 75) (IVT 14.8% vs direct MT 22.2%, p = 0.272), nor in male patients (IVT 43.3% vs direct 29.4%, p = 0.065) or female patients (IVT 24.7% vs direct 25.7%, p = 0.888). (Tables S1 and S2) Discussion This study was a multi-centre retrospective cohort study conducted across 3 large comprehensive stroke centres across Europe. In this study, we found that patients who received bridging IVT prior to MT failed to achieve better functional outcomes compared to those who received direct MT alone. Interestingly, in the subgroup of patients with ICA occlusion due to large artery atherosclerosis, bridging IVT was associated with better functional outcomes. Some recent studies demonstrate that patients who receive bridging IVT prior to MT achieve higher rates of favourable functional outcomes compared to patients who receive direct MT. 25,26 A possible explanation for this could be that systemic thrombolysis lyses the remaining small thrombi that MT is unable to remove. 27 Additionally, it assists in lysing any distal emboli which might have been dislodged during the passes of thrombectomy device during the MT procedure. 27 As bridging IVT might shorten in-hospital rehabilitation times and facilitate early discharges, it could be beneficial to employ this treatment modality in ICA occlusion acute ischaemic strokes. 28 , 29 It is recommended for patients to seek treatment early so that they present within the window for bridging IVT. However, results from our study contradict this. It instead shows similar rates of favourable mRS scores between patients who have underwent IVT and those who underwent direct MT both upon discharge and at 90-days after discharge. Recent large-scale studies support our findings that bridging IVT does not improve long-term functional outcomes. 28 , 29 This phenomenon is not unique to ischaemic strokes due to internal carotid artery occlusion. In fact, it is also echoed in acute ischaemic strokes due to the occlusion of other large vessels, such as the basilar artery in the posterior circulation. 30 A possible explanation for this is that MT alone is often successful in achieving vessel recanalisation, and the effect of distal emboli and migration of thrombi to new territories in the brain is minimal. 31 , 32 Therefore, a short course of intensive rehabilitation in the in-patient setting 33 is potentially sufficient to overcome the initial disparity in functional outcomes between the bridging IVT group and the direct MT group, allowing the direct MT group to achieve similar rates of favourable functional outcomes as their peers in the long run. The main complication from IVT is that of bleeding, with ICH and bleeding in the gastrointestinal tract causing more significant morbidity compared to bleeding elsewhere. 34 If severe, these bleeding manifestations could lead to increased duration of hospitalisation and poorer functional outcomes. 35 Notably, the rates of systemic haemorrhagic manifestations are low in both the bridging IVT group and the direct MT group in our study. 36 Despite previous literature on the theoretical risks of bleeding complications, bridging IVT was also not demonstrated to lead to a higher rate of bleeding complications compared to direct MT in this study. Although the results of the present study suggest that bridging IVT does not seem to improve the overall long-term functional outcomes of patients with ICA occlusion, there might be a subgroup of patients that might benefit from bridging IVT. Further subgroup analysis revealed that patients with LAA who received bridging IVT achieved both better short term and long-term functional outcomes. 37 – 39 In LAA, the existing narrowing of cerebral vessels triggers the formation of collateral vessels over time. 40 It is postulated that the thrombolytic agent flows through collateral vessels as well, allowing it to reach the distal end of the thrombus more effectively, in comparison to embolic strokes and strokes of other aetiologies where the collateral circulation development is more limited. 41 , 42 Additionally, in LAA strokes with intracranial stenosis, it can be technically challenging to remove the thrombus via MT due to the narrowed lumen of cerebral vessels, with the potential to re-occlude. 43 , 44 Administration of IVT potentially softens or dissolves the thrombus, facilitating more effective MT and better patient outcomes. Therefore, there is a stronger case for administration of bridging IVT in patients with LAA compared to the general population. The limitations of our study stem from its retrospective non-randomized nature. Due to the non-randomized nature and lack of blinding of our study, treatment allocations were made at the discretion of the treating stroke neurologist and neurointerventionist. This may introduce selection bias as different centres may have different clinical practices. To mitigate this, analysis was performed to show that the two treatment groups were relatively homogeneous in terms of baseline characteristics. Additionally, our findings are reflective of real-world treatment paradigms as they reflect the same inconsistencies observed in treatment allocations by different physicians even within the same centre, facilitating our improved understanding of the appropriate therapeutic strategies. Another limitation of our study is the lack of data on NIHSS scores at discharge which can show early improvements post recanalization therapy. Conclusion Bridging IVT is not associated with better functional outcomes compared to direct MT in ICA stroke. However, in the subgroup of patients with underlying large-artery atherosclerosis stroke mechanism, bridging IVT appears to potentially confer beneficial outcomes. Declarations Human Ethics and Consent to Participate declarations Not applicable. Conflicts of Interest: The authors have no conflict of interest to report. Funding: This study is funded in part by the National Medical Research Council, Singapore (NMRC/MOH-TA19Nov-0003). Author Contribution I.S. and K.S.L wrote the main manuscript text and L.Y. supervised the project. All authors reviewed the manuscript. Acknowledgement The authors thank our patients and their families for their valuable contribution to the study. 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Stroke Vasc Interv Neurol 2(4):e000129. 10.1161/SVIN.121.000129 Cai J, Xu H, Xiao R et al (2023) Rescue intracranial stenting for acute ischemic stroke after the failure of mechanical thrombectomy: A systematic review, meta-analysis, and trial sequential analysis. Front Neurol 14:1023089. 10.3389/fneur.2023.1023089 Additional Declarations No competing interests reported. Supplementary Files ICAstrokeresultsV3Copy.docx ICAstrokesupplementarydataV1.docx Cite Share Download PDF Status: Published Journal Publication published 21 Jan, 2026 Read the published version in Neuroradiology → 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. 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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-7901947","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":538479200,"identity":"274135ac-7361-4063-bde5-4f66be5c2e06","order_by":0,"name":"Isabel Siow","email":"","orcid":"","institution":"Ministry of Health Holdings Singapore","correspondingAuthor":false,"prefix":"","firstName":"Isabel","middleName":"","lastName":"Siow","suffix":""},{"id":538479204,"identity":"15f4b207-40d4-4688-a40c-a01465b216fc","order_by":1,"name":"Keng Siang Lee","email":"","orcid":"","institution":"National Neuroscience 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16:11:28","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":888765,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-7901947/v1/7c9bdd14-2667-4321-ba1d-a162e6cbf14a.pdf"},{"id":95013801,"identity":"40bc7a72-93cb-44f1-9ca6-cfd96123fbf0","added_by":"auto","created_at":"2025-11-03 10:47:34","extension":"docx","order_by":0,"title":"","display":"","copyAsset":false,"role":"supplement","size":26036,"visible":true,"origin":"","legend":"","description":"","filename":"ICAstrokeresultsV3Copy.docx","url":"https://assets-eu.researchsquare.com/files/rs-7901947/v1/b7dde241b4bcef295fafd9d7.docx"},{"id":95220935,"identity":"c0b7bd83-1f86-4385-99cf-6f7e64adfc8c","added_by":"auto","created_at":"2025-11-05 16:17:13","extension":"docx","order_by":1,"title":"","display":"","copyAsset":false,"role":"supplement","size":25288,"visible":true,"origin":"","legend":"","description":"","filename":"ICAstrokesupplementarydataV1.docx","url":"https://assets-eu.researchsquare.com/files/rs-7901947/v1/db76aa88ad4a795f8e6858fd.docx"}],"financialInterests":"No competing interests reported.","formattedTitle":"Bridging Thrombolysis Does Not Achieve Better Outcomes Compared to Direct Mechanical Thrombectomy in Stroke Due to Internal Carotid Artery Occlusion","fulltext":[{"header":"Introduction","content":"\u003cp\u003eInternal carotid artery (ICA) occlusion affects approximately 15% of patients with acute ischaemic stroke secondary to large vessel occlusion.\u003csup\u003e\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e\u003c/sup\u003e Without treatment, it frequently leads to adverse outcomes, causing significant rates of morbidity and mortality. In patients who present within the time window, the standard of care for ICA occlusion is mechanical thrombectomy (MT).\u003csup\u003e\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e\u003c/sup\u003e Administration of bridging intravenous thrombolysis (IVT) prior to MT is also commonly recommended in patients with no contraindications.\u003csup\u003e\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e\u003c/sup\u003e The main aim of IVT is to assist in achieving recanalisation of the culprit vessel.\u003csup\u003e\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e\u003c/sup\u003e Additionally, if MT succeeds, bridging IVT can potentially assist in dissolution of distal emboli that might have been dislodged during the MT procedure. However, bridging IVT is not without risks.\u003csup\u003e\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e\u003c/sup\u003e Intracranial haemorrhage and gastrointestinal bleeding can result in severe adverse outcomes.\u003csup\u003e\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e\u003c/sup\u003e\u003c/p\u003e\u003cp\u003eSeveral recent large-scale studies on the efficacy of bridging IVT prior to MT have revealed conflicting results. Some studies report equivalent effects achieved in bridging IVT and direct MT\u003csup\u003e6\u003c/sup\u003e while others report superior functional outcomes in patients with bridging IVT.\u003csup\u003e\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e,\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e\u003c/sup\u003e As such, an optimal clinical management protocol in patients with ICA occlusion has yet to be established.\u003c/p\u003e\u003cp\u003eWe therefore performed a multi-centre retrospective cohort study conducted across 3 large comprehensive stroke centres across Europe to determine whether bridging IVT as opposed to direct MT alone would be beneficial in patients with ICA occlusion acute ischaemic stroke.\u003c/p\u003e"},{"header":"Methods","content":"\u003cp\u003eEthics and standard protocol approvals\u003c/p\u003e\u003cp\u003e This retrospective cohort study was approved by the National University Health System Institutional Review Board (ID: DSRB 2019/00252). A waiver of individual participant consent was granted.\u003c/p\u003e\u003cp\u003ePatients and treatment\u003c/p\u003e\u003cp\u003eConsecutive patients from three comprehensive stroke centers across Europe with ICA occlusion acute ischaemic stroke who underwent MT between January 2015 and December 2019 were included. Of these, patients with a premorbid modified Rankin Scale (mRS)\u0026thinsp;\u0026ge;\u0026thinsp;2 were excluded from this study.\u003csup\u003e\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e\u003c/sup\u003e Prior to MT, all patients underwent baseline neurovascular imaging with computed tomography (CT) and CT angiography. Patients were considered for bridging thrombolysis if they presented within 4.5 hours of symptom onset, if they had no contraindications, and administration was at the final discretion of the treating stroke neurologist.\u003csup\u003e\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e\u003c/sup\u003e In each institution, IVT was administered by an accredited neurologist at a dose of 0.9 mg/kg.\u003csup\u003e8\u003c/sup\u003e\u003c/p\u003e\u003cp\u003eAt all centers, patients were considered eligible for MT if the procedure could be initiated within 24 hours of the time of stroke onset and had an angiographically confirmed occlusion in the internal carotid artery. Patients with tandem lesions were included in the study. Patients were excluded from thrombectomy when pre-treatment imaging revealed extensive ischemic changes, or if the stroke was considered mild based on an admission National Institutes of Health Stroke Scale (NIHSS) score of 3 or less.\u003csup\u003e\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e\u003c/sup\u003e\u003c/p\u003e\u003cp\u003eClinical monitoring was performed in either the intensive care unit or high dependency unit setting during the initial acute episode.\u003csup\u003e\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e\u003c/sup\u003e All patients were managed according to international guidelines for the management of AIS.\u003csup\u003e\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e\u003c/sup\u003e Participating stroke centers employed either a stent-retriever, direct aspiration catheter, or combined stent-retriever and aspiration via intermediate catheter approach from the start of the procedure, this was at the discretion of the interventionist. Follow-up CT scan was performed at around 24 hours after initial treatment.\u003csup\u003e\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e\u003c/sup\u003e\u003c/p\u003e\u003cp\u003eData collection\u003c/p\u003e\u003cp\u003eThe following epidemiological information was extracted from patient records: age, sex, race, and smoking history. Comorbidities studied included hypertension, hyperlipidaemia, diabetes mellitus, atrial fibrillation, and previous ischemic stroke. These conditions were defined based on guidelines by the World Health Organization\u003csup\u003e\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e\u003c/sup\u003e and American Heart Association\u003csup\u003e\u003cspan additionalcitationids=\"CR14\" citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e\u003c/sup\u003e. The mechanism of ischemic stroke was defined according to the Trial of ORG 10172 in Acute Stroke Treatment (TOAST) classification,\u003csup\u003e16\u003c/sup\u003e NIHSS score\u003csup\u003e\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e\u003c/sup\u003e on admission and the time from stroke onset to groin puncture were extracted.\u003c/p\u003e\u003cp\u003ePrimary and secondary outcomes\u003c/p\u003e\u003cp\u003eThe primary outcome measure was a favorable functional outcome defined by mRS\u0026thinsp;\u0026le;\u0026thinsp;2 after 90 days. Secondary measures of outcome were in-hospital mortality, good functional outcome defined as mRS\u0026thinsp;\u0026le;\u0026thinsp;2 at discharge, and rates of complications such as spontaneous intracranial hemorrhage (sICH), subarachnoid hemorrhage (SAH) and embolisation to new territories. Other secondary measures of outcome were favourable functional outcome as defined by mRS\u0026thinsp;\u0026le;\u0026thinsp;3 after 90 days and mRS\u0026thinsp;\u0026le;\u0026thinsp;3 at discharge. Further subgroup analyses were performed to evaluate the effect of bridging IVT against direct MT in the subgroups of patients with large artery atherosclerosis (LAA), good premorbid condition (premorbid mRS 0\u0026ndash;1), young age (\u0026le;\u0026thinsp;75 years), advanced age (\u0026gt;\u0026thinsp;75 years),\u003csup\u003e18\u003c/sup\u003e male sex and female sex. Reperfusion was assessed using post-procedure angiography, and successful reperfusion was defined as having a 2b\u0026ndash;3 flow as calculated using the modified Thrombolysis in Cerebral Infarction (mTICI) scale. Additionally, a subset of patients who achieved mTICI 2c and 3 grades reperfusion was also tabulated. sICH was defined by the presence of parenchymal hemorrhage with an increase in NIHSS by \u0026ge;\u0026thinsp;4 points within 24 hours of revascularization according to the modified Safe Implementation of Thrombolysis in Stroke-Monitoring Study (SITS-MOST) criteria.\u003csup\u003e\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e\u003c/sup\u003e Any SAH present in the 24-hour post-thrombectomy CT scan was included in the definition.\u003c/p\u003e\u003cdiv id=\"Sec3\" class=\"Section2\"\u003e\u003ch2\u003eStatistical analysis\u003c/h2\u003e\u003cp\u003eNumeric variables were first tested for normality with the Shapiro-Wilk test. A Student\u0026rsquo;s t-test was used for normally distributed data and a Mann-Whitney U test for non-normally distributed data. Categorical variables were compared using a Pearson chi-square test, with computation of Wald and score 95% confidence interval (CI) for the incidence odds ratio (OR). Subsequently, multivariable logistic regression was carried out to identify predictors for primary and secondary outcome measures. In addition, the following exploratory subgroup analyses were performed: (1) age 75 years or younger vs. older than 75 years; (2) male vs. female sex; and (3) TOAST mechanism of large-artery atherosclerosis (LAA) vs. non-LAA strokes. P values\u0026thinsp;\u0026lt;\u0026thinsp;0.05 were considered statistically significant. The selection of variables for multivariable analyses was decided a priori, including age,\u003csup\u003e20\u003c/sup\u003e sex,\u003csup\u003e21\u003c/sup\u003e NIHSS\u003csup\u003e\u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e\u003c/sup\u003e and time from stroke onset to groin puncture.\u003csup\u003e\u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e\u003c/sup\u003e These were selected based on past literature which demonstrated that they have a significant impact on functional outcomes after MT. Unknown or missing values were excluded from the denominator when calculating proportions in the study cohort. All statistical analysis was performed using SPSS version 26 (IBM Co., Armonk, NY, USA).\u003c/p\u003e\u003c/div\u003e"},{"header":"Results","content":"\u003cp\u003eBaseline characteristics\u003c/p\u003e\n\u003cp\u003eA total of 352 patients were included in the study. Of these patients, 178 (50.6%) patients underwent bridging IVT prior to MT and 174 (49.4%) underwent direct MT. The baseline characteristics of the bridging IVT group and direct MT group were comparable, with similar age, race, and sex. Notably, more patients in the direct MT group had hyperlipidaemia and atrial fibrillation compared to those in the bridging IVT group. In accordance with TOAST classification, 106 patients (44.5%) had underlying LAA and 107 patients (45.0%) had stroke due to cardioembolism, 16 patients had stroke of other determined aetiology (6.7) and 9 patients had stroke of undetermined aetiology (3.8%). Stroke severity as measured by median NIHSS was similar between the two groups at a median of 16. Median time from stroke onset to groin puncture was longer in the direct MT group (median, 351.3 minutes; interquartile range [IQR], 347.9), compared to the bridging thrombolysis group (median, 256.6 minutes; IQR, 159.8; p\u0026thinsp;=\u0026thinsp;0.004). Median time from groin puncture to reperfusion was similar between both groups. (Table \u003cspan class=\"InternalRef\"\u003e1\u003c/span\u003e)\u003c/p\u003e\n\u003cdiv class=\"gridtable\"\u003e\n \u003ctable id=\"Tab1\" border=\"1\"\u003e\n \u003ccaption\u003e\n \u003cdiv class=\"CaptionNumber\"\u003eTable 1\u003c/div\u003e\n \u003cdiv class=\"CaptionContent\"\u003e\n \u003cp\u003eBaseline characteristics of study population\u003c/p\u003e\n \u003c/div\u003e\n \u003c/caption\u003e\n \u003cthead\u003e\n \u003ctr\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eCharacteristic\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eDirect MT (N\u0026thinsp;=\u0026thinsp;174)\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eBridging IVT\u003c/p\u003e\n \u003cp\u003e(N\u0026thinsp;=\u0026thinsp;178)\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eTotal (N\u0026thinsp;=\u0026thinsp;352)\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003ep-value\u003c/p\u003e\n \u003c/th\u003e\n \u003c/tr\u003e\n \u003c/thead\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eAge, Mean\u0026thinsp;\u0026plusmn;\u0026thinsp;SD\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e70.3\u0026thinsp;\u0026plusmn;\u0026thinsp;14.4\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e69.3\u0026thinsp;\u0026plusmn;\u0026thinsp;14.9\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e69.8\u0026thinsp;\u0026plusmn;\u0026thinsp;14.6\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.500\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eSex, N (%)\u003c/p\u003e\n \u003cp\u003eMale\u003c/p\u003e\n \u003cp\u003eFemale\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e91 (52.3)\u003c/p\u003e\n \u003cp\u003e83 (47.7)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e88 (49.4)\u003c/p\u003e\n \u003cp\u003e90 (50.6)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e179 (50.9)\u003c/p\u003e\n \u003cp\u003e173 (49.1)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e0.591\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eCountry, N (%)\u003c/p\u003e\n \u003cp\u003eGermany\u003c/p\u003e\n \u003cp\u003eUnited Kingdom\u003c/p\u003e\n \u003cp\u003eSweden\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e102 (58.6)\u003c/p\u003e\n \u003cp\u003e17 (9.8)\u003c/p\u003e\n \u003cp\u003e55 (31.6)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e108 (60.7)\u003c/p\u003e\n \u003cp\u003e14 (7.9)\u003c/p\u003e\n \u003cp\u003e56 (31.5)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e210 (59.7)\u003c/p\u003e\n \u003cp\u003e31 (8.8)\u003c/p\u003e\n \u003cp\u003e111 (31.5)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e0.808\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eRace\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e(all Caucasian)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eHypertension, N (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e83 (69.7)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e80 (65.6)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e163 (67.6)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.489\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eHyperlipidaemia, N (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e29 (25.9)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e16 (13.9)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e45 (19.8)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.024\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eDiabetes mellitus, N (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e25 (21.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e21 (17.2)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e46 (19.1)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.454\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eAtrial fibrillation, N (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e60 (50.4)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e39 (32.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e99 (41.1)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.004\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003ePrevious stroke, N (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e14 (11.8)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e7 (5.7)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e21 (8.7)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.097\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eSmoker\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e18 (16.7)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e16 (14.4)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e34(15.5)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.645\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eTOAST classification, N (%)\u003c/p\u003e\n \u003cp\u003eLarge-artery atherosclerosis\u003c/p\u003e\n \u003cp\u003eCardioembolic\u003c/p\u003e\n \u003cp\u003eStroke of other determined aetiology\u003c/p\u003e\n \u003cp\u003eStroke of undetermined aetiology\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e45 (38.1)\u003c/p\u003e\n \u003cp\u003e61 (51.7)\u003c/p\u003e\n \u003cp\u003e8 (6.8)\u003c/p\u003e\n \u003cp\u003e4 (3.4)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e61 (50.8)\u003c/p\u003e\n \u003cp\u003e46 (38.3)\u003c/p\u003e\n \u003cp\u003e8 (6.7)\u003c/p\u003e\n \u003cp\u003e5 (4.2)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e106 (44.5)\u003c/p\u003e\n \u003cp\u003e107 (45.0)\u003c/p\u003e\n \u003cp\u003e16 (6.7)\u003c/p\u003e\n \u003cp\u003e9 (3.8)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e0.202\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eAdmission NIHSS, Median\u0026thinsp;\u0026plusmn;\u0026thinsp;IQR\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e16.0\u0026thinsp;\u0026plusmn;\u0026thinsp;7.0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e17.0\u0026thinsp;\u0026plusmn;\u0026thinsp;8.0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e16.0\u0026thinsp;\u0026plusmn;\u0026thinsp;8.0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.153\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eTime from stroke onset to groin puncture\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e351.3\u0026thinsp;\u0026plusmn;\u0026thinsp;347.9\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e256.6\u0026thinsp;\u0026plusmn;\u0026thinsp;159.8\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e298.5\u0026thinsp;\u0026plusmn;\u0026thinsp;264.2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.004\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eTime from groin puncture to reperfusion\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e62.0\u0026thinsp;\u0026plusmn;\u0026thinsp;128.0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e66.9\u0026thinsp;\u0026plusmn;\u0026thinsp;120.9\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e64.5\u0026thinsp;\u0026plusmn;\u0026thinsp;124.3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.725\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n \u003c/table\u003e\n\u003c/div\u003e\n\u003cp\u003ePrimary outcome\u003c/p\u003e\n\u003cp\u003eRates of favourable functional outcomes as defined by 90-day mRS 0\u0026ndash;2 were similar between the bridging IVT group and the direct MT group (33.5% vs 27.7%, p\u0026thinsp;=\u0026thinsp;0.255). (Table\u0026nbsp;\u003cspan class=\"InternalRef\"\u003e2\u003c/span\u003e) After adjustment for age, sex, NIHSS and time from stroke onset to groin puncture in the multivariable model, there was still no significant difference in rates of favourable functional outcomes between the two groups (OR\u0026thinsp;=\u0026thinsp;1.34; 95% CI 0.76\u0026ndash;2.38; p\u0026thinsp;=\u0026thinsp;0.317). (Table\u0026nbsp;\u003cspan class=\"InternalRef\"\u003e3\u003c/span\u003e)\u003c/p\u003e\n\u003cdiv class=\"gridtable\"\u003e\n \u003cdiv class=\"colspec\" align=\"left\"\u003e\u0026nbsp;\u003c/div\u003e\n \u003ctable id=\"Tab2\" border=\"1\"\u003e\n \u003ccaption\u003e\n \u003cdiv class=\"CaptionNumber\"\u003eTable 2\u003c/div\u003e\n \u003cdiv class=\"CaptionContent\"\u003e\n \u003cp\u003eComparison of outcomes between direct MT and bridging IVT groups\u003c/p\u003e\n \u003c/div\u003e\n \u003c/caption\u003e\n \u003cthead\u003e\n \u003ctr\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eOutcome\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eDirect MT (N\u0026thinsp;=\u0026thinsp;174)\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eBridging IVT\u003c/p\u003e\n \u003cp\u003e(N\u0026thinsp;=\u0026thinsp;178)\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eTotal (N\u0026thinsp;=\u0026thinsp;352)\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003ep-value\u003c/p\u003e\n \u003c/th\u003e\n \u003c/tr\u003e\n \u003c/thead\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eDischarge mRS, N (%)\u003c/p\u003e\n \u003cp\u003e0\u0026ndash;2\u003c/p\u003e\n \u003cp\u003e3\u0026ndash;6\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e21 (17.8)\u003c/p\u003e\n \u003cp\u003e97 (82.8)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e35 (28.9)\u003c/p\u003e\n \u003cp\u003e86 (71.1)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e56 (23.4)\u003c/p\u003e\n \u003cp\u003e183 (76.6)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e0.042\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eDischarge mRS, N (%)\u003c/p\u003e\n \u003cp\u003e0\u0026ndash;3\u003c/p\u003e\n \u003cp\u003e4\u0026ndash;6\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e29 (24.6)\u003c/p\u003e\n \u003cp\u003e89 (75.4)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e46 (38.0)\u003c/p\u003e\n \u003cp\u003e75 (62.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e75 (31.4)\u003c/p\u003e\n \u003cp\u003e164 (68.4)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e0.025\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e90-day mRS, N (%)\u003c/p\u003e\n \u003cp\u003e0\u0026ndash;2\u003c/p\u003e\n \u003cp\u003e3\u0026ndash;6\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e44 (27.7)\u003c/p\u003e\n \u003cp\u003e115 (72.3)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e54 (33.5)\u003c/p\u003e\n \u003cp\u003e107 (66.5)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e98 (30.6)\u003c/p\u003e\n \u003cp\u003e222 (69.4)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e0.255\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e90-day mRS, N (%)\u003c/p\u003e\n \u003cp\u003e0\u0026ndash;3\u003c/p\u003e\n \u003cp\u003e4\u0026ndash;6\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e61 (38.4)\u003c/p\u003e\n \u003cp\u003e98 (61.6)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e71 (44.1)\u003c/p\u003e\n \u003cp\u003e90 (55.9)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e132 (41.3)\u003c/p\u003e\n \u003cp\u003e188 (58.8)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e0.297\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eInpatient mortality, N (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e41 (23.7)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e34 (19.2)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e75 (21.4)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.306\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eTICI post-treatment, N (%)\u003c/p\u003e\n \u003cp\u003e0-2a (poor)\u003c/p\u003e\n \u003cp\u003e2b-3 (good)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e33 (19.4)\u003c/p\u003e\n \u003cp\u003e137 (80.6)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e35 (20.0)\u003c/p\u003e\n \u003cp\u003e140 (80.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e68 (19.7)\u003c/p\u003e\n \u003cp\u003e277 (80.3)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e0.891\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eTICI post-treatment, N (%)\u003c/p\u003e\n \u003cp\u003e0-2b (poor)\u003c/p\u003e\n \u003cp\u003e2c-3 (good)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e78 (45.9)\u003c/p\u003e\n \u003cp\u003e92 (54.1)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e95 (54.3)\u003c/p\u003e\n \u003cp\u003e80 (45.7)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e173 (50.1)\u003c/p\u003e\n \u003cp\u003e172 (49.9)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e0.119\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003esICH, N (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e23 (13.2)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e30 (16.9)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e53 (15.1)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.340\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eSAH, N (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e8 (4.6)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e8 (4.5)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e16 (4.5)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.963\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eEmbolisation to new territory, N (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e11 (6.5)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e5 (3.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e16 (4.7)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.130\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n \u003c/table\u003e\n\u003c/div\u003e\n\u003cdiv class=\"gridtable\"\u003e\n \u003cdiv class=\"colspec\" align=\"left\"\u003e\u0026nbsp;\u003c/div\u003e\n \u003ctable id=\"Tab3\" border=\"1\"\u003e\n \u003ccaption\u003e\n \u003cdiv class=\"CaptionNumber\"\u003eTable 3\u003c/div\u003e\n \u003cdiv class=\"CaptionContent\"\u003e\n \u003cp\u003eComparison of outcomes between bridging IVT and direct MT groups\u003c/p\u003e\n \u003c/div\u003e\n \u003c/caption\u003e\n \u003cthead\u003e\n \u003ctr\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eOutcome\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eModel 1\u003c/p\u003e\n \u003cp\u003eOR (91% CI); p-value\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eModel 2*\u003c/p\u003e\n \u003cp\u003eOR (91% CI); p-value\u003c/p\u003e\n \u003c/th\u003e\n \u003c/tr\u003e\n \u003c/thead\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eDischarge mRS, N (%)\u003c/p\u003e\n \u003cp\u003e0\u0026ndash;2 vs 3\u0026ndash;6\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e1.88 (1.02\u0026ndash;3.47); 0.044\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e1.77 (0.86\u0026ndash;3.64); 0.123\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eDischarge mRS, N (%)\u003c/p\u003e\n \u003cp\u003e0\u0026ndash;3 vs 4\u0026ndash;6\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e1.88 (1.08\u0026ndash;3.29); 0.026\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e2.13 (1.10\u0026ndash;4.13); 0.025\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e90-day mRS, N (%)\u003c/p\u003e\n \u003cp\u003e0\u0026ndash;2 vs 3\u0026ndash;6\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e1.32 (0.82\u0026ndash;2.13); 0.255\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e1.34 (0.76\u0026ndash;2.38); 0.317\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e90-day mRS, N (%)\u003c/p\u003e\n \u003cp\u003e0\u0026ndash;3 vs 4\u0026ndash;6\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e1.27 (0.81\u0026ndash;1.98); 0.298\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e1.293 (0.75\u0026ndash;2.22); 0.353\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eInpatient mortality, N (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e1.31 (0.78\u0026ndash;2.18); 0.307\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e1.18 (0.65\u0026ndash;2.13); 0.587\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003emTICI post-treatment, N (%)\u003c/p\u003e\n \u003cp\u003e0-2a (poor) vs 2b-3 (good)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e1.04 (0.61\u0026ndash;1.77); 0.891\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e1.10 (0.60\u0026ndash;2.03); 0.763\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003emTICI post-treatment, N (%)\u003c/p\u003e\n \u003cp\u003e0-2b (poor) vs 2c-3 (good)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e1.40 (0.92\u0026ndash;2.14); 0.119\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e1.42 (0.88\u0026ndash;2.29); 0.155\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003esICH\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.75 (0.42\u0026ndash;1.35); 0.341\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.62 (0.31\u0026ndash;1.25); 0.184\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eSAH\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e1.02 (0.38\u0026ndash;2.79); 0.963\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.56 (0.15\u0026ndash;2.06); 0.380\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eEmbolisation to new territory\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e2.26 (0.77\u0026ndash;6.64); 0.140\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e2.27 (0.64\u0026ndash;8.07); 0.207\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n \u003ctfoot\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"3\"\u003e*adjusted for age, sex, NIHSS and time from stroke onset to groin puncture\u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tfoot\u003e\n \u003c/table\u003e\n\u003c/div\u003e\n\u003cp\u003eSecondary outcomes\u003c/p\u003e\n\u003cp\u003eSecondary outcomes were largely similar between the direct MT group and the bridging IVT group. On univariate analysis, patients in the bridging IVT group had higher rates of favourable mRS on discharge compared to those in the direct MT group (28.9% vs 17.8%, P\u0026thinsp;=\u0026thinsp;0.042). (Table\u0026nbsp;\u003cspan class=\"InternalRef\"\u003e2\u003c/span\u003e) However, after adjustment for age, sex, NIHSS and time from stroke onset to groin puncture in the multivariable model, bridging IVT was no longer significantly associated with favorable mRS scores on discharge (OR\u0026thinsp;=\u0026thinsp;1.77; 95% CI 0.86\u0026ndash;3.64; p-0.123). (Table\u0026nbsp;\u003cspan class=\"InternalRef\"\u003e3\u003c/span\u003e) A similar proportion of patients achieved successful reperfusion (mTICI 2b\u0026ndash;3) in the direct MT group and the bridging IVT group (80.6% and 80.0%, p\u0026thinsp;=\u0026thinsp;0.891). In-hospital mortality rate was also similar between the direct MT group (23.7%) and the bridging IVT group (19.2%) (p\u0026thinsp;=\u0026thinsp;0.306). Few patients sustained hemorrhagic complications, such as sICH (16.9% in the bridging IVT group vs 13.2% in the direct MT group) and SAH (4.5% in the bridging IVT group vs 4.6% in the direct MT group). Further analysis was performed with favourable functional outcomes at discharge and at 90 days defined as mRS 0\u0026ndash;3. This was because ICA strokes and strokes with tandem lesions tend to yield worse outcomes than MCA strokes.\u003csup\u003e\u003cspan class=\"CitationRef\"\u003e24\u003c/span\u003e\u003c/sup\u003e (Table\u0026nbsp;\u003cspan class=\"InternalRef\"\u003e2\u003c/span\u003e)\u003c/p\u003e\n\u003cp\u003eSubgroup analyses\u003c/p\u003e\n\u003cp\u003eA significant treatment effect of bridging IVT was observed in the subgroup of patients who had underlying LAA (Table \u003cspan class=\"InternalRef\"\u003e4\u003c/span\u003e). In this subgroup, patients treated with bridging IVT compared to direct MT had a high rate of favorable functional outcome at discharge (37.7% vs. 18.2%, p\u0026thinsp;=\u0026thinsp;0.030). Patients treated with bridging IVT still had a higher rate of favorable functional outcome at 90 days (33.9% vs 14.0%, p\u0026thinsp;=\u0026thinsp;0.022). Notably, patients treated with bridging IVT had lower rates of SAH (0% vs 11.1%, p\u0026thinsp;=\u0026thinsp;0.012). Rates of in-hospital mortality and rates of other complications such as sICH and embolisation of clots to new territories were comparable between the two groups. (Table \u003cspan class=\"InternalRef\"\u003e4\u003c/span\u003e)\u003c/p\u003e\n\u003cdiv class=\"gridtable\"\u003e\n \u003ctable id=\"Tab4\" border=\"1\"\u003e\n \u003ccaption\u003e\n \u003cdiv class=\"CaptionNumber\"\u003eTable 4\u003c/div\u003e\n \u003cdiv class=\"CaptionContent\"\u003e\n \u003cp\u003eSubgroup analysis comparing outcomes of bridging IVT vs. direct MT in internal carotid artery stroke with underlying large artery atherosclerosis (n\u0026thinsp;=\u0026thinsp;105)\u003c/p\u003e\n \u003c/div\u003e\n \u003c/caption\u003e\n \u003cthead\u003e\n \u003ctr\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eOutcome\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eDirect MT (N\u0026thinsp;=\u0026thinsp;44)\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eBridging IVT\u003c/p\u003e\n \u003cp\u003e(N\u0026thinsp;=\u0026thinsp;61)\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eTotal (N\u0026thinsp;=\u0026thinsp;105)\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003ep-value\u003c/p\u003e\n \u003c/th\u003e\n \u003c/tr\u003e\n \u003c/thead\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eDischarge mRS, N (%)\u003c/p\u003e\n \u003cp\u003e0\u0026ndash;2\u003c/p\u003e\n \u003cp\u003e3\u0026ndash;6\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e6 (13.6)\u003c/p\u003e\n \u003cp\u003e38 (86.4)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e17 (27.9)\u003c/p\u003e\n \u003cp\u003e44 (72.1)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e23 (21.9)\u003c/p\u003e\n \u003cp\u003e82 (78.1)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e0.082\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eDischarge mRS, N (%)\u003c/p\u003e\n \u003cp\u003e0\u0026ndash;3\u003c/p\u003e\n \u003cp\u003e4\u0026ndash;6\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e8 (18.2)\u003c/p\u003e\n \u003cp\u003e36 (81.8)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e23 (37.7)\u003c/p\u003e\n \u003cp\u003e38 (62.3)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e31 (29.5)\u003c/p\u003e\n \u003cp\u003e74 (70.5)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e0.030\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e90-day mRS, N (%)\u003c/p\u003e\n \u003cp\u003e0\u0026ndash;2\u003c/p\u003e\n \u003cp\u003e3\u0026ndash;6\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e6 (14.0)\u003c/p\u003e\n \u003cp\u003e37 (86.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e20 (33.9)\u003c/p\u003e\n \u003cp\u003e39 (66.1)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e26 (25.5)\u003c/p\u003e\n \u003cp\u003e76 (74.5)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e0.022\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e90-day mRS, N (%)\u003c/p\u003e\n \u003cp\u003e0\u0026ndash;3\u003c/p\u003e\n \u003cp\u003e4\u0026ndash;6\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e13 (30.2)\u003c/p\u003e\n \u003cp\u003e30 69.8)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e23 (39.0)\u003c/p\u003e\n \u003cp\u003e36 (61.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e36 (35.3)\u003c/p\u003e\n \u003cp\u003e66 (64.7)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e0.361\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eInpatient mortality, N (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e15 (34.1)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e18 (29.5)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e33 (31.4)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.618\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eTICI post-treatment, N (%)\u003c/p\u003e\n \u003cp\u003e0-2a (poor)\u003c/p\u003e\n \u003cp\u003e2b-3 (good)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e12 (27.3)\u003c/p\u003e\n \u003cp\u003e32 (72.7)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e14 (23.3)\u003c/p\u003e\n \u003cp\u003e46 (76.7)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e26 (25.0)\u003c/p\u003e\n \u003cp\u003e78 (75.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e0.647\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eTICI post-treatment, N (%)\u003c/p\u003e\n \u003cp\u003e0-2b (poor)\u003c/p\u003e\n \u003cp\u003e2c-3 (good)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e28 (63.6)\u003c/p\u003e\n \u003cp\u003e16 (36.4)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e35 (58.3)\u003c/p\u003e\n \u003cp\u003e25 (41.7)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e63 (60.6)\u003c/p\u003e\n \u003cp\u003e41 (39.4)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e0.585\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003esICH, N (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e8 (17.8)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e8 (13.1)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e16 (15.5)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.507\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eSAH, N (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e5 (11.1)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0 (0.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e5 (4.7)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.012\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eEmbolisation to new territory, N (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e3 (6.7)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0 (0.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e3 (2.9)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.076\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n \u003c/table\u003e\n\u003c/div\u003e\n\u003cp\u003eIn all other subgroup analyses performed, there were no significant differences in the rates of favorable functional outcome at 90 days between the bridging IVT group and the direct MT group. Specifically, bridging IVT did not improve outcomes at 90 days in patients with good premorbid function (mRS 0\u0026ndash;1)( IVT 38.5% vs direct MT 31.5%, p\u0026thinsp;=\u0026thinsp;0.242), in the subgroup of patients who were young (age\u0026thinsp;\u0026le;\u0026thinsp;75) (IVT 45.0% vs direct MT 32.2%, p\u0026thinsp;=\u0026thinsp;0.073), in the older patients (age\u0026thinsp;\u0026gt;\u0026thinsp;75) (IVT 14.8% vs direct MT 22.2%, p\u0026thinsp;=\u0026thinsp;0.272), nor in male patients (IVT 43.3% vs direct 29.4%, p\u0026thinsp;=\u0026thinsp;0.065) or female patients (IVT 24.7% vs direct 25.7%, p\u0026thinsp;=\u0026thinsp;0.888). (Tables S1 and S2)\u003c/p\u003e"},{"header":"Discussion","content":"\u003cp\u003eThis study was a multi-centre retrospective cohort study conducted across 3 large comprehensive stroke centres across Europe. In this study, we found that patients who received bridging IVT prior to MT failed to achieve better functional outcomes compared to those who received direct MT alone. Interestingly, in the subgroup of patients with ICA occlusion due to large artery atherosclerosis, bridging IVT was associated with better functional outcomes.\u003c/p\u003e\u003cp\u003eSome recent studies demonstrate that patients who receive bridging IVT prior to MT achieve higher rates of favourable functional outcomes compared to patients who receive direct MT.\u003csup\u003e25,26\u003c/sup\u003e A possible explanation for this could be that systemic thrombolysis lyses the remaining small thrombi that MT is unable to remove.\u003csup\u003e\u003cspan citationid=\"CR27\" class=\"CitationRef\"\u003e27\u003c/span\u003e\u003c/sup\u003e Additionally, it assists in lysing any distal emboli which might have been dislodged during the passes of thrombectomy device during the MT procedure.\u003csup\u003e\u003cspan citationid=\"CR27\" class=\"CitationRef\"\u003e27\u003c/span\u003e\u003c/sup\u003e As bridging IVT might shorten in-hospital rehabilitation times and facilitate early discharges, it could be beneficial to employ this treatment modality in ICA occlusion acute ischaemic strokes.\u003csup\u003e\u003cspan citationid=\"CR28\" class=\"CitationRef\"\u003e28\u003c/span\u003e,\u003cspan citationid=\"CR29\" class=\"CitationRef\"\u003e29\u003c/span\u003e\u003c/sup\u003e It is recommended for patients to seek treatment early so that they present within the window for bridging IVT.\u003c/p\u003e\u003cp\u003eHowever, results from our study contradict this. It instead shows similar rates of favourable mRS scores between patients who have underwent IVT and those who underwent direct MT both upon discharge and at 90-days after discharge. Recent large-scale studies support our findings that bridging IVT does not improve long-term functional outcomes.\u003csup\u003e\u003cspan citationid=\"CR28\" class=\"CitationRef\"\u003e28\u003c/span\u003e,\u003cspan citationid=\"CR29\" class=\"CitationRef\"\u003e29\u003c/span\u003e\u003c/sup\u003e This phenomenon is not unique to ischaemic strokes due to internal carotid artery occlusion. In fact, it is also echoed in acute ischaemic strokes due to the occlusion of other large vessels, such as the basilar artery in the posterior circulation.\u003csup\u003e\u003cspan citationid=\"CR30\" class=\"CitationRef\"\u003e30\u003c/span\u003e\u003c/sup\u003e A possible explanation for this is that MT alone is often successful in achieving vessel recanalisation, and the effect of distal emboli and migration of thrombi to new territories in the brain is minimal.\u003csup\u003e\u003cspan citationid=\"CR31\" class=\"CitationRef\"\u003e31\u003c/span\u003e,\u003cspan citationid=\"CR32\" class=\"CitationRef\"\u003e32\u003c/span\u003e\u003c/sup\u003e Therefore, a short course of intensive rehabilitation in the in-patient setting\u003csup\u003e\u003cspan citationid=\"CR33\" class=\"CitationRef\"\u003e33\u003c/span\u003e\u003c/sup\u003e is potentially sufficient to overcome the initial disparity in functional outcomes between the bridging IVT group and the direct MT group, allowing the direct MT group to achieve similar rates of favourable functional outcomes as their peers in the long run.\u003c/p\u003e\u003cp\u003eThe main complication from IVT is that of bleeding, with ICH and bleeding in the gastrointestinal tract causing more significant morbidity compared to bleeding elsewhere.\u003csup\u003e\u003cspan citationid=\"CR34\" class=\"CitationRef\"\u003e34\u003c/span\u003e\u003c/sup\u003e If severe, these bleeding manifestations could lead to increased duration of hospitalisation and poorer functional outcomes.\u003csup\u003e\u003cspan citationid=\"CR35\" class=\"CitationRef\"\u003e35\u003c/span\u003e\u003c/sup\u003e Notably, the rates of systemic haemorrhagic manifestations are low in both the bridging IVT group and the direct MT group in our study.\u003csup\u003e\u003cspan citationid=\"CR36\" class=\"CitationRef\"\u003e36\u003c/span\u003e\u003c/sup\u003e Despite previous literature on the theoretical risks of bleeding complications, bridging IVT was also not demonstrated to lead to a higher rate of bleeding complications compared to direct MT in this study.\u003c/p\u003e\u003cp\u003eAlthough the results of the present study suggest that bridging IVT does not seem to improve the overall long-term functional outcomes of patients with ICA occlusion, there might be a subgroup of patients that might benefit from bridging IVT. Further subgroup analysis revealed that patients with LAA who received bridging IVT achieved both better short term and long-term functional outcomes.\u003csup\u003e\u003cspan additionalcitationids=\"CR38\" citationid=\"CR37\" class=\"CitationRef\"\u003e37\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR39\" class=\"CitationRef\"\u003e39\u003c/span\u003e\u003c/sup\u003e In LAA, the existing narrowing of cerebral vessels triggers the formation of collateral vessels over time.\u003csup\u003e\u003cspan citationid=\"CR40\" class=\"CitationRef\"\u003e40\u003c/span\u003e\u003c/sup\u003e It is postulated that the thrombolytic agent flows through collateral vessels as well, allowing it to reach the distal end of the thrombus more effectively, in comparison to embolic strokes and strokes of other aetiologies where the collateral circulation development is more limited.\u003csup\u003e\u003cspan citationid=\"CR41\" class=\"CitationRef\"\u003e41\u003c/span\u003e,\u003cspan citationid=\"CR42\" class=\"CitationRef\"\u003e42\u003c/span\u003e\u003c/sup\u003e Additionally, in LAA strokes with intracranial stenosis, it can be technically challenging to remove the thrombus via MT due to the narrowed lumen of cerebral vessels, with the potential to re-occlude.\u003csup\u003e\u003cspan citationid=\"CR43\" class=\"CitationRef\"\u003e43\u003c/span\u003e,\u003cspan citationid=\"CR44\" class=\"CitationRef\"\u003e44\u003c/span\u003e\u003c/sup\u003e Administration of IVT potentially softens or dissolves the thrombus, facilitating more effective MT and better patient outcomes. Therefore, there is a stronger case for administration of bridging IVT in patients with LAA compared to the general population.\u003c/p\u003e\u003cp\u003eThe limitations of our study stem from its retrospective non-randomized nature. Due to the non-randomized nature and lack of blinding of our study, treatment allocations were made at the discretion of the treating stroke neurologist and neurointerventionist. This may introduce selection bias as different centres may have different clinical practices. To mitigate this, analysis was performed to show that the two treatment groups were relatively homogeneous in terms of baseline characteristics. Additionally, our findings are reflective of real-world treatment paradigms as they reflect the same inconsistencies observed in treatment allocations by different physicians even within the same centre, facilitating our improved understanding of the appropriate therapeutic strategies. Another limitation of our study is the lack of data on NIHSS scores at discharge which can show early improvements post recanalization therapy.\u003c/p\u003e"},{"header":"Conclusion","content":"\u003cp\u003eBridging IVT is not associated with better functional outcomes compared to direct MT in ICA stroke. However, in the subgroup of patients with underlying large-artery atherosclerosis stroke mechanism, bridging IVT appears to potentially confer beneficial outcomes.\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eHuman Ethics and Consent to Participate declarations\u003c/strong\u003e\u003cp\u003eNot applicable.\u003c/p\u003e\u003c/p\u003e\u003cp\u003e\u003ch2\u003eConflicts of Interest:\u003c/h2\u003e\u003cp\u003eThe authors have no conflict of interest to report.\u003c/p\u003e\u003c/p\u003e\u003ch2\u003eFunding:\u003c/h2\u003e\u003cp\u003eThis study is funded in part by the National Medical Research Council, Singapore (NMRC/MOH-TA19Nov-0003).\u003c/p\u003e\u003ch2\u003eAuthor Contribution\u003c/h2\u003e\u003cp\u003eI.S. and K.S.L wrote the main manuscript text and L.Y. supervised the project. All authors reviewed the manuscript.\u003c/p\u003e\u003ch2\u003eAcknowledgement\u003c/h2\u003e\u003cp\u003eThe authors thank our patients and their families for their valuable contribution to the study.\u003c/p\u003e\u003ch2\u003eData Availability\u003c/h2\u003e\u003cp\u003eAnonymised data that support the findings of this study are available from the corresponding author upon reasonable request.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\u003cli\u003e\u003cspan\u003eRubiera M, Ribo M, Delgado-Mederos R et al (2006) Tandem internal carotid artery/middle cerebral artery occlusion: an independent predictor of poor outcome after systemic thrombolysis. 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Front Neurol 14:1023089. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.3389/fneur.2023.1023089\u003c/span\u003e\u003cspan address=\"10.3389/fneur.2023.1023089\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":true,"highlight":"","institution":"","isAcceptedByJournal":true,"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":"","lastPublishedDoi":"10.21203/rs.3.rs-7901947/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-7901947/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003eBackground and purpose. Mechanical thrombectomy (MT) is an effective treatment for patients with acute ischaemic stroke secondary to internal carotid artery (ICA) occlusion. Intravenous thrombolysis (IVT) prior to MT is also commonly administered in suitable patients. This study aimed to compare the outcomes of patients with acute ICA stroke who were treated with direct MT versus combined IVT plus MT. Additionally, analysis was performed in different subgroups of patients such as those with large artery stenosis (LAA) to evaluate which subgroup of patients would benefit most from bridging IVT.\u003c/p\u003e\u003cp\u003eMethods. This multicenter retrospective cohort study included patients who were treated for acute ICA stroke from three comprehensive stroke centers between January 2015 and December 2019. Patients received direct MT or combined bridging IVT plus MT. Primary outcome was favorable functional outcome defined as modified Rankin Scale (mRS) 0\u0026ndash;2 measured at 90 days after discharge. Secondary outcome measures included mRS on discharge, inpatient mortality and complications such as symptomatic intracranial hemorrhage (sICH), subarachnoid haemorrhage (SAH) and embolism of thrombus to new territories.\u003c/p\u003e\u003cp\u003eResults. Among 352 patients, 178 (50.6%) patients underwent bridging IVT followed by MT and 174 (49.4%) underwent direct MT. The mean\u0026thinsp;\u0026plusmn;\u0026thinsp;standard deviation age was 69.8\u0026thinsp;\u0026plusmn;\u0026thinsp;14.6 years, 50.9% were male and median National Institutes of Health Stroke Scale was 16 (interquartile range). At 90-days after discharge, patients who underwent bridging IVT had similar functional outcomes as those who underwent direct MT (33.5% vs 27.7%, P\u0026thinsp;=\u0026thinsp;0.255). On multivariable analyses, bridging IVT was not associated with improvement in discharge mRS score, 90-day mRS score, decreased mortality or difference in rate of complications compared to direct MT. In subgroup analyses, patients with underlying atherosclerosis treated with bridging IVT compared to direct MT had a higher rate of favorable functional outcome at 90 days (33.9% vs. 14.0%, P\u0026thinsp;=\u0026thinsp;0.022)\u003c/p\u003e\u003cp\u003eConclusions. Bridging IVT is not associated with better functional outcomes compared to direct MT in ICA stroke. However, in the subgroup of patients with underlying large-artery atherosclerosis stroke mechanism, bridging IVT appears to potentially confer beneficial outcomes. 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