Introduction: Meta-analyses of RCTs of intravenous alteplase (IVT) for stroke with unknown time of onset (SUTO), selected by advanced imaging have shown better functional outcomes than placebo or standard care, but with higher mortality and symptomatic intracerebral hemorrhage (SICH). A balanced assessment of benefits and harms is therefore needed. Hypothesis: Desirability of Outcome Ranking (DOOR) methods may provide a comprehensive assessment of benefits and harms that closely reflect the patient's experience in IVT for SUTO. Methods: The Evaluation of Unknown Onset Stroke Thrombolysis (EOS) collaboration included four RCTs comparing IVT with standard care or placebo. DOOR analysis was applied to individual patient-level data. Patients were assigned a DOOR rank (1-10) based on 90-day mRS, SICH, major extracranial bleeding, and lack of NIHSS improvement ≥2 points at 24 hr. Ranks were: (1) mRS 0–1 with no undesirable events; (2) mRS 0–1 with 1 event (SICH, major extracranial bleeding, or lack of NIHSS improvement); (3) mRS 0–1 with >1 events; (4) mRS 2–3 with no events; (5) mRS 2–3 with 1 event; (6) mRS 2–3 with >1 events; (7) mRS 4–5 with no events; (8) mRS 4–5 with 1 event; (9) mRS 4–5 with >1 events; (10) death. DOOR probability and win ratio were calculated. Results: Among 829 patients (420 IVT, 409 controls), DOOR probability was 0.55 (95% CI, 0.51–0.59; p = 0.011) and win ratio was 1.24 (95% CI, 1.22-1.25), indicating a 55% probability and a 1.24 times higher frequency of achieving a more desirable outcome with IVT compared with control (Fig 1, 2). A forest plot shows that IVT was associated with a lower proportion of patients with poor functional outcome (mRS 4–5: 15.0% vs. 21.5%) and a higher proportion of NIHSS improvement (57.6% vs. 48.9%), but a higher rate of death (6.4% vs. 3.4%) and SICH/major extracranial bleeding (3.3% vs. 0.5%) compared to controls (Fig 2). Additionally, a sequential dichotomization analysis of DOOR rankings revealed that the DOOR probability remained above 50% across most dichotomization thresholds. The greatest separation was observed at DOOR > 4 vs. ≤4, with a probability of 54.8% (95% CI, 51.4–58.1) (Fig 3). Conclusions: DOOR analysis demonstrated a more desirable overall outcome with IVT for SUTO. The results suggest that IVT was associated with more favorable DOOR ranking, particularly within the better DOOR ranking strata that reflect a favorable balance between clinical efficacy and safety.

Abstract Background and aims Advanced trial design features are increasingly used in stroke. The MSU Telemedicine trial is a recent example, demonstrating that on a Mobile Stroke Unit (MSU), a telemedicine model of care improved resource efficiency with minimal delays in clinical decision-making and no difference in safety. We provide an in-depth discussion of how advanced trial design features can be combined to effectively address research questions in stroke, using MSU Telemedicine as a case study. Methods MSU Telemedicine was a covariate-adjusted, cluster-randomised clinical trial with the Win Odds as its primary outcome measure. It had three key features: use of the “Win Odds” to address a multifaceted research question; covariate-adaptive randomisation to prospectively balance prognostic covariates; and a cluster-randomised design, which facilitated randomisation at the daily level, as individual participant randomisation was impractical. Results MSU Telemedicine achieved this combination of features by applying a novel modification to Simon and Pocock’s Biased Coin Algorithm that balanced the number of participants seen by nurses with different levels of experience using the anticipated number of participants that would be seen each day. To account for this randomisation procedure, p-values for the Win Odds were estimated using re-randomisation tests in accordance with FDA guidelines on adaptive randomisation, while confidence intervals were estimated using clustered bootstrap that accounted for daily clustering. Conclusions The combined use of advanced trial design features equips stroke researchers to improve stroke care. This combined approach is achievable in practice, as evidenced by the MSU Telemedicine Trial. Conflict of interest HJ: Nothing to disclose. VY: Nothing to disclose. AB: Nothing to disclose. BC: Nothing to disclose. SD: Nothing to disclose. GD: Nothing to disclose. LC: Nothing to disclose.

Background Spontaneous intracerebral haemorrhage (ICH) has high rates of mortality with no proven haemostatic treatment. We conducted the first systematic review and individual patient data meta-analysis (IPDMA) to assess the effect of tranexamic acid on outcomes in spontaneous ICH.Methods We searched databases such as MEDLINE, EMBASE and CENTRAL for randomised controlled trials comparing intravenous tranexamic acid to placebo in adults with spontaneous ICH treated within 12 hours. The primary outcome was 90-day functional status (modified Rankin scale). Secondary outcomes included early mortality and haematoma expansion. One-stage random-effects analysis used generalised linear mixed models. Risk of bias was assessed using the Cochrane Risk of Bias (RoB) 2 tool.Results We screened 1131 records; nine trials (3194 participants) met inclusion and five trials (2860 participants; 90%) provided individual patient data. ROB was low in all trials. At 90 days, 53.2% of patients receiving tranexamic acid had a worse functional outcome compared with 53.6% in the placebo (adjusted common OR 0.93, 95% CI 0.81 to 1.07). Mortality at day 7 and haematoma expansion were significantly reduced with tranexamic acid (adjusted OR 0.70, 95% CI 0.51 to 0.95; and OR 0.81, 95% CI 0.68 to 0.97). No between-trial heterogeneity was observed.Conclusions This systematic review and IPDMA of tranexamic acid for spontaneous ICH found no improvement in 90-day functional outcomes. However, small yet significant reductions in early mortality and haematoma expansion were observed. The early mortality benefit and favourable safety profile support further research into ultra-early treatment and as part of ICH care bundles for selected patient populations.PROSPERO registration number CRD42017054978.

Introduction: Access to time-critical stroke therapy, particularly remotely, is limited by the distance to travel to stationary brain scanners. A lightweight (<15kg), backpack sized ‘First Responder’ brain scanner has been developed utilising non-ionising electromagnetic (ultra-high frequency radio) signals for urgent stroke diagnosis. A brain scan is completed in minutes for the purposes of stroke classification and localisation, which is then transmitted to a telehealth connected neurologist. The study aims to evaluate the implementation of the First Responder brain scanner into the aeromedical retrieval workflow. Methods: This workflow implementation study will enrol aeromedical retrieval patients over an 8 week period (approximately 30 participants). Lower acuity aeromedical retrievals (e.g. non-emergency medical condition or interhospital transfer) will be initially targeted for enrolment to ensure patient safety is prioritised. Brain scans with the First Responder brain scanner will be completed in the field at the location of retrieval. Workflow metrics will be evaluated including time-on-scene, scan procedure duration, and telehealth network connectivity. The device’s safety, reliability, scan quality and usability will also be evaluated, as well as participant experience. Results: Preliminary results have demonstrated that the First Responder device withstood the rigors of aeromedical flight and successfully completed 3 healthy volunteer scans in rural South Australia. Scan sites included a remote community (Marree) and regional centre (Port Augusta), spanning distances of approximately 245-970km (45-105 minute flight) from Adelaide air base. Successful scans of healthy volunteers allowed advancement to patients subject to aeromedical retrieval. The aeromedical clinical study is now underway, enrolling patients across rural South Australia. Full implementation data will be presented. Conclusions: This study represents the world-first aeromedical integration of a miniaturised brain scanner capable of real-time, rural and remote stroke diagnosis. The device demonstrated operational resilience, scan fidelity, and workflow compatibility under retrieval conditions. Pending clinical validation, this model offers a pathway to reshape stroke systems of care: decentralising diagnosis, accelerating triage and potential treatment, and closing stroke care equity gaps for remote populations.

Introduction: The predictive value of CT markers of intracerebral haemorrhage (ICH) expansion is time-dependent, but data in the ultra-early period (<2 h from onset) are limited. We aimed to describe the frequency of these CT markers, their association with haematoma volume, haematoma expansion (HE) and functional outcome at 90-days. We also investigated the effect of tranexamic acid on HE in the presence of these markers. Patients and methods: We performed a pooled analysis of individual patient data from the STOP-AUST and STOP-MSU placebo-controlled randomised trials of tranexamic acid, including ICH patients scanned within 2 h of symptom onset. Logistic regression was used to assess the association between CT markers and HE or 90-days functional outcomes (poor outcome defined as mRS3-6). Results: Among 246 patients, the swirl sign (74.3%) was the most frequent CT marker and the blend sign least frequent (7.3%). All markers were associated with increased baseline haematoma volume, and excluding the black hole sign, all were more common in patients with 24-h HE. The blend and spot signs were associated with 24-h HE and heterogenous density, swirl sign, hypodensity and island sign were associated with poor 90-day function outcomes in univariate logistic regression. However, the area under the receiver-operating-characteristic curve was similar for all markers and indicated low discriminative ability (Chi-squared test p = 0.81). A potential benefit of tranexamic acid in HE reduction was observed in patients with the spot sign (interaction p = 0.01) Conclusions: The discriminative utility of CT markers of HE in the early timeframe appears insufficient. There may be an effect of tranexamic acid in spot sign positive patients <2 h from onset.

Background: Identifying patients likely to have significant hematoma expansion (HE) has been a challenge in clinical trials of intracerebral hemorrhage (ICH). Non-contrast CT (NCCT) markers of HE have been described. Time from symptom onset to CT affects the predictive value of these markers, with limited data in the ultra-early time period (<3h from onset). We aimed to describe the frequency of NCCT markers in the ultra-early period of ICH, and their association with HE. Methods: We performed a pooled analysis of individual patient data from the STOP-AUST and STOP-MSU randomized controlled trials, which tested the effect of tranexamic acid on hematoma growth. We included ICH patients scanned within 2 hours of symptom onset. The presence of NCCT density and shape markers was assessed by two authors. HE was defined as an increase in hematoma volume of >33% or >6ml from baseline. Regression analyses were adjusted for treatment group and baseline hematoma volume. Results: There were 246 patients included in this analysis (median age 67 years, 38.8% female, median time from onset to imaging 75 min [IQR 59-88 min], 50.4% tranexamic acid), of whom 105 (42.7%) had HE on 24-hour imaging. Inter-rater agreement was excellent for all NCCT markers (kappa score >0.8). Most patients (85.7%) had ≥1 marker of HE. The most frequent marker was the swirl sign (74.3%) and the least frequent was the blend sign (7.3%) (Table 1). HE occurred more often in patients with any marker at baseline (45.5% vs 25.6%, p=0.03). The blend sign (15.2% vs 1.4%, p<0.01), island sign (38.1% vs 24.8%, p=0.01) and satellite sign (44.8% vs 34.8%, p=0.04) were more common in patients with HE than those without. The presence of any marker was not independently associated with HE (aOR1.63 [95%CI 0.70-3.80], p=0.26). The blend sign was the only sign independently associated with HE (aOR 11.58 [95%CI 2.57-52.19], p=0.01). On diagnostic performance for HE, specificity was highest for the blend sign (0.99, 95% CI 0.95-1.00), with limited sensitivity of 0.15 (95%CI 0.09-0.24) (Table 1). The area under the receiver operator curve showed similar values for all markers suggesting low discriminative ability (Delong test p=0.81). Conclusions: NCCT markers are commonly present in the ultra-early period of ICH and associated with subsequent hematoma growth. Despite association with HE, the discriminative utility in the early timeframe appears insufficient, and the search for an optimal target should continue.

Objectives: Knowledge of the trajectory of post-stroke depression is important to identify high-risk patients, develop precise management programs and enhance prognosis. We aimed to characterise the course of depressive symptoms within the first year post-stroke and to evaluate associations with time.Materials and Methods: Depressive symptoms were measured using the Montgomery-Åsberg Depression Rating Scale (MADRS) within the first week, and at 3- and 12-months post-stroke. Scores were dichotomised into symptoms ‘present’ (MADRS ≥ 7) or ‘absent’ (MADRS < 7). The course of depressive symptoms within individuals was mapped and categorised using a trajectory diagram. The association between time and the presence of depressive symptoms was investigated using random effects logistic regression. Logistic regression was also used to assess the likelihood of participants having depressive symptoms later, given their status at earlier time points.Results: Of 142 ischaemic stroke survivors included for analysis, almost half (47.9%) experienced a change in depressive symptom status over time. Depressive symptoms were common at each timepoint (35-43%), although an association between time and frequency of depressive symptoms was not evident. Stroke survivors with depressive symptoms at 3 months were more likely to have depressive symptoms at 12 months, compared to those without symptoms at 3 months.Conclusion: Our findings provide evidence for a dynamic trajectory of depressive symptoms in individuals in the first year post-stroke. The importance of repeated screening for depression is highlighted, though most necessary at 3 months post-stroke.

BACKGROUND:We aimed to determine whether extensive severe computed tomography (CT) hypodensity, representing blood-brain barrier injury, would be associated with a reduced benefit of endovascular therapy (EVT) in patients presenting with large core stroke. METHODS:This study is an exploratory analysis of SELECT2 (Randomized Controlled Trial to Optimize Patient's Selection for Endovascular Treatment in Acute Ischemic Stroke), a randomized controlled trial of EVT versus medical management in patients with large ischemic core who presented to 31 comprehensive stroke centers across the United States, Canada, Europe, Australia, and New Zealand. Visible CT hypodensity was outlined, and a threshold of severe CT hypodensity was defined as the lower 99% CI of contralateral thalamic gray matter in Hounsfield units (HU). The association between the volume of severe CT hypodensity and modified Rankin Scale (mRS) score of 0 to 3 was evaluated using logistic regression models, with adjustment for age, National Institutes of Health Stroke Scale, total noncontrast CT core volume, and a volume-by-treatment interaction. The relationship between severe CT hypodensity volume and the probability of an mRS score of 0 to 3 was used to select clinically relevant volume cut points for further evaluation. The treatment effect of EVT versus medical management on independent ambulation and hemicraniectomy was assessed in 2 subgroups based on these volume cut points. RESULTS:In 322 patients, the median CT density was 31 HU (interquartile range, 28-34). The selected threshold of severe CT hypodensity was 26 HU. The volume of ischemic core ≤26 HU (per 1 mL increase) was associated with lower odds of mRS score of 0 to 3 after EVT (adjusted odds ratio [aOR], 0.96 [95% CI, 0.94-0.99]), but not medical management (aOR, 1.01 [95% CI, 0.98-1.03]; Pinteraction<0.01). In 101 patients with ≥26 mL of severe CT hypodensity, EVT, compared with medical management, was not associated with mRS score of 0 to 3 (aOR, 0.98 [95% CI, 0.33-2.88]) and was associated with hemicraniectomy (≥26 mL: aOR, 3.45 [95% CI, 1.09-10.86] versus <26 mL: aOR, 0.74 [95% CI, 0.31-1.75]; Pinteraction=0.03), whereas among 221 patients with <26 mL of severe hypodensity EVT was associated with mRS score of 0 to 3 (aOR, 7.20 [95% CI, 3.55-15.47]; Pinteraction<0.01). CONCLUSIONS:Severe hypodensity within large ischemic regions modifies the thrombectomy treatment effect and increases the likelihood of hemicraniectomy, independent of lesion volume. REGISTRATION:URL: https://www.clinicaltrials.gov; Unique identifier: NCT03876457.

Background Diagnosis of occult atrial fibrillation (AF) is difficult as it is often asymptomatic, leading to under detection. Current diagnostic tests have variable limitations in feasibility and accuracy. Machine learning is gaining greater traction for clinical decision making and may help facilitate the detection of undiagnosed AF when applied to magnetic resonance imaging (MRI). We hypothesise that machine learning algorithm increases the accurate classification of MRIs of stroke patients into those due to AF vs large artery atherosclerosis. Methods Stroke aetiology for each patient was determined by a review of medical records and investigations. Patients with either AF or large artery atherosclerosis were included. Patients were randomly divided into the training and validation groups (4:1). A 3D convolutional neural network (ConvNeXt) was developed to train and validate the algorithm. After training, the models were evaluated using common metrics for binary classification. Results A total of 235 patients were analysed (97 with AF, 138 without AF). The mean age of the sample was 71.1 (SD 14.2) and 35% percent were female. The best discriminative performance was obtained in the 5th fold of cross-validation (AUC-ROC 0.88) and the overall model performance was 0.81. The best performing metrics were precision (0.84) and the F1-score (0.77). Conclusion Our machine learning algorithm has reasonable classification power in categorizing stroke patients into those with and without underlying AF. Testing in external validation data sets are critical to confirm these results.

BACKGROUND:Evidence of the cost implications and health outcomes associated with the use of mobile stroke units (MSU) is required to support their utilization. We aimed to evaluate the causal effect of the use of an MSU compared with a standard ambulance on hospitalization costs and 90- to 180-day health outcomes. METHODS:Causal effect estimation was performed using patient-level data from a cohort of patients with stroke in 2018 identified from the Australian Stroke Clinical Registry (Victoria) and Melbourne MSU. These data were linked to Ambulance Victoria and government-held administrative data sets. In total, linked data from 8657 patients were available. Propensity score matching was used to define comparator groups within a target trial framework. Costs included emergency department and hospital admission costs in the first 180 days after stroke. Multivariable regression analyses of the matched data were used to compare costs and outcomes (mortality and modified Rankin Scale) between MSU and standard ambulance groups. RESULTS:The target trial sample included 96 patients transported by the MSU (intervention) and 198 patients transported by standard ambulance services (control). Of these, the mean age was 76 years and 157 (53%) were men. A greater proportion of patients received mechanical thrombectomy in the intervention group than the control group (40% versus 23%; P<0.001). The adjusted hospital costs were $17 949 greater in the intervention group than the control group (95% CI, $4682-$31 214; P=0.01). Patients in intervention group doubled the odds of achieving nondisability (modified Rankin Scale scores of 0-1, adjusted odds ratio of 2.11 [95% CI, 1.07-4.18]) and halved the mortality rate (adjusted hazard ratio, 0.53 [95% CI, 0.32-0.86]) within 90 to 180 days poststroke compared with the control group. CONCLUSIONS:There are important cost implications and improved outcomes from using the MSU that are likely related to increased provision of reperfusion therapy.

The association of anesthesia approach during endovascular thrombectomy (EVT) with clinical outcomes in large strokes is unexplored. We aimed to evaluate whether general anesthesia (GA), compared with non-GA, was associated with better functional outcomes in the SELECT2 trial. In a prespecified secondary analysis of the SELECT2 trial that enrolled patients with large strokes on noncontrast CT (Alberta Stroke Program Early CT Score [ASPECTS] 3-5), CT perfusion/MRI (core volume ≥50 mL), or both, functional outcomes were compared in EVT-treated patients who received GA or non-GA and whether this association was modified by stroke severity (NIH Stroke Scale score), ischemic injury estimates, and collateral status was evaluated. The primary outcome was 90-day functional status (ordinal modified Rankin Scale [mRS]). Secondary outcomes were functional independence (mRS scores 0-2), independent ambulation (mRS scores 0-3), complete dependence or death (mRS scores 5-6), and mortality. Of 178 EVT patients (median [interquartile range] age 66 [58-75] years, stroke severity 19 [15-23], CT-ASPECTS 4 [3-5], and core volume 101.5 [70-138] mL, 71 women [39.9%]), 104 (58%) received GA. Time from randomization to arterial puncture was longer with GA (40 [23-59] minutes) vs non-GA (27 [18-47] minutes), but procedural duration (GA: 57 [31.5-77] minutes vs non-GA: 49.5 [30-71] minutes) was similar. Successful reperfusion (modified treatment in cerebral infarction [mTICI] score 2b-3) rates were similar (GA 81 (78%) vs non-GA 62 (84%), adjusted relative risk [aRR] 0.91, 95% CI 0.79-1.06). In addition, mRS distribution did not differ between GA and non-GA groups (adjusted generalized odds ratio 1.21, 95% CI 0.86-1.70), as well as independent ambulation (GA: 41% vs non-GA: 34%, aRR 1.22, 95% CI 0.86-1.74) and functional independence (GA: 22% vs non-GA: 18%, aRR 1.32, 95% CI 0.75-2.35). Stroke severity, ASPECTS, ischemic core volume, or collaterals did not modify the association between anesthesia and functional outcome (all p-interaction >0.05). Patients experienced systolic blood pressure (SBP) variability ≥40 mm Hg and minimum intraprocedural SBP (<100 mm Hg) more frequently with GA, but this did not modify GA association with functional outcomes (p-interaction = 0.77 and 0.89, respectively). In patients with large core strokes randomized in SELECT2, EVT outcomes did not differ significantly based on anesthesia approach (GA or non-GA) without heterogeneity across stroke severity and size. While GA was associated with higher SBP variability and lower minimum SBP, this did not modify GA association with functional outcomes. While allocation to anesthesia approach was nonrandomized, our findings suggest that optimizing institutional protocols for preferred anesthesia technique, whether GA or non-GA, may enhance EVT procedural outcomes. ClinicalTrials.gov ID: NCT03876457. This study provides Class II evidence that in patients presenting within 24 hours with large vessel occlusion strokes undergoing EVT, the 90-day mRS score is comparable in those with or without GA.

Background The incidence of intracerebral hemorrhage (ICH) and its effect on the outcomes after endovascular thrombectomy (EVT) for patients with large core infarcts have not been well-characterized. Methods SELECT2 trial follow-up imaging was evaluated using the Heidelberg Bleeding Classification (HBC) to define hemorrhage grade. The association of ICH with clinical outcomes and treatment effect was examined. Results Of 351 included patients, 194 (55%) and 189 (54%) demonstrated intracranial and intracerebral hemorrhage, respectively, with a higher incidence in EVT (134 (75%) and 130 (73%)) versus medical management (MM) (60 (35%) and 59 (34%), both P<0.001). Hemorrhagic infarction type 1 (HBC=1a) and type 2 (HBC=1b) accounted for 93% of all hemorrhages. Parenchymal hematoma (PH) type 1 (HBC=1c) and type 2 (HBC=2) were observed in 1 (0.6%) EVT-treated and 4 (2.2%) MM patients. Symptomatic ICH (sICH) (SITS-MOST definition) was seen in 0.6% EVT patients and 1.2% MM patients. No trend for ICH with core volumes (P=0.10) or Alberta Stroke Program Early CT Score (ASPECTS) (P=0.74) was observed. Among EVT patients, the presence of any ICH did not worsen clinical outcome (modified Rankin Scale (mRS) at 90 days: 4 (3-6) vs 4 (3-6); adjusted generalized OR 1.00, 95% CI 0.68 to 1.47, P>0.99) or modify EVT treatment effect (P-interaction=0.77). Conclusions ICH was present in 75% of the EVT population, but PH or sICH were infrequent. The presence of any ICH did not worsen functional outcomes or modify EVT treatment effect at 90-day follow-up. The high rate of hemorrhages overall still represents an opportunity for adjunctive therapies in EVT patients with a large ischemic core.

More than half of the endovascularly treated ischemic stroke patients with incomplete reperfusion (expanded Thrombolysis in Cerebral Infarction [eTICI] <3) show delayed reperfusion (DR) on 24-hour perfusion imaging, which is associated with favorable clinical outcome. The effect of intravenous thrombolysis (IVT) on the rates of DR remains unclear. This study aimed to assess the treatment effect of IVT on the occurrence of DR. Pooled data from 3 randomized controlled trials (EXTEND-IA and EXTEND-IA TNK parts 1 and 2) and 2 comprehensive stroke centers (University Hospitals Graz and Bern) were analyzed. Only patients with a final reperfusion score of eTICI 2a-2c and available perfusion imaging at follow-up of 24 ± 12 hours were included. The primary outcome was the presence of DR on 24-hour follow-up CT/MRI perfusion imaging, defined as the absence of any focal perfusion deficit on perfusion imaging, despite incomplete reperfusion on the final angiography series during thrombectomy. For the secondary analysis, we explored the association between the primary outcome (DR) and the time elapsed between start of IVT and the end of an intervention. To address confounding in observational data, we performed a target trial emulation. Of 832 included patients with eTICI 2a-2c (median age 74 years, 49% female), 511 (61%) had DR. There was an independent treatment effect of IVT on DR (standardized risk ratio [sRR] 1.1, 95% CI 1.0-1.3; standardized risk difference [sRD] 8.2%, 95% CI 0.2%-16.1%), after adjusting for age, sex, atrial fibrillation, number of device passes, collateral score, and eTICI. Among those patients who have received IVT (n = 524/832, 63%), when adjusting for the aforementioned covariates, there was a causal effect of shorter time between administration of thrombolytics and end of the intervention on DR (sRR 0.93%, 95% CI 0.87-0.98; sRD -5.2%; 95% CI -9.1% to -1.3%, per hour increase). Exposure to thrombolytics showed independent treatment effect on the occurrence of DR among patients with incomplete reperfusion after thrombectomy who undergo perfusion imaging at the 24-hour follow-up. The effect of thrombolytics on DR was observed if there was a high chance of therapeutic concentrations of thrombolytics at the time point when the proximal vessel was recanalized, but distal occlusions persisted and/or occurred. This study is rated Class III because it is a nonrandomized study and there are substantial differences in baseline characteristics of the treatment groups.

Introduction: Little is known of the long-term prognosis of patients with acute ischaemic stroke in the absence of standard modifiable stroke risk factors (SMoRFs). In acute coronary syndromes, patients without modifiable risk factors have a higher mortality rate. We analysed data from the Swedish Stroke Register to determine survival of patients without SMoRFs following an ischaemic stroke. Patients and methods: We identified adult patients with first-presentation acute ischaemic stroke between 2010 and 2020. Patients were considered to possess a SMoRF if they had one of: hypertension, diabetes, hyperlipidaemia, atrial fibrillation or an active smoking history. We compared mortality in patients with and without SMoRFs following first-presentation ischaemic stroke using cox regression models. We also assessed the combined endpoint death and dependency (mRS 3–6) at 3 months via logistic regression models. Results: Of 152,588 patients with ischaemic stroke, hypertension (58.7%) and atrial fibrillation (27.3%) were the most common risk factors. 34,019 patients (22.3%) had no SMoRFs. After a first-presentation ischaemic stroke, patients without SMoRFs had a lower risk of death than patients with one or more SMoRFs (HR 0.58 [95% CI 0.57–0.59]). The absence of SMoRFs was associated with lower odds of death and dependency at 3 months in logistic regression models (OR 0·60 [95% CI 0.58–0.62]). Conclusion: One in five patients with acute ischaemic stroke had no standard modifiable stroke risk factors. These patients have lower risk of death compared to patients with one or more SMoRFs.

Background:Repeat imaging when regional and remote patients with stroke arrive at a comprehensive stroke center can delay endovascular thrombectomy. We examined outcomes amongs patients transferred for endovascular therapy from nonmetropolitan primary stroke centers. Methods:In this prospective observational study patients who were transferred from remote nonmetropolitan hospitals with large vessel occlusion were recruited between 2020-2023. The control group was defined as patients with repeat neuroimaging at the comprehensive stroke center in the radiology/emergency department. Direct-to-angio (direct to angiography) included patients who proceeded directly to the angiography suite without any repeat neuroimaging or routine flat panel computed tomography. Logistic regression with propensity matching was performed to assess factors associated with 3-month independent outcome (modified Rankin scale score 0-2). A secondary analysis was performed to assess factors associated with recanalization. Results:Between June 2020 and February 2023, 227 patients with large vessel occlusion were transferred for endovascular clot retrieval. A total of 47 (26%) patients recanalized by time of arrival and 180 had persistent large vessel occlusion. Primary stroke centers were a median distance of 185 km from the comprehensive stroke center (interquartile range 130-256). After propensity matching 138 patients remained. Characteristics between direct-to-angio and control groups were similar with regard to age (68 versus 66), primary stroke centers National Institutes of Health Stroke Scale score (15 versus 13), and onset to referral (200 versus 246 min). Direct-to-angio increased independent functional outcome at 3 months (adjusted odds ratio, 2.2 [95% CI, 1.0-4.9]; P = 0.05). Direct-to-angio resulted in shorter door-to arterial puncture time (43 versus 77 min, P<0.001) and a higher likelihood of receiving endovascular therapy (100% versus 65%, P<0.001). Conclusion:In patients who have already received telestroke review at the primary stroke centers, our results suggest a direct-to-angio approach is likely to result in better outcomes.

Background: The effects of intravenous alteplase in patients with prior antiplatelet therapy (APT) remain controversial. We aimed to assess the efficacy and safety of imaging-based intravenous alteplase in patients with unknown onset stroke with prior APT. Methods: Data from randomized controlled trials comparing alteplase with placebo/standard care in patients with unknown onset acute ischemic stroke from the Evaluation of Unknown Onset Stroke Thrombolysis (EOS) individual patient data meta-analysis collaboration were analyzed. Favorable outcome was defined as a modified Rankin Scale score of 0–1 at 90 days post-stroke. Safety outcomes included symptomatic intracranial hemorrhage (sICH) at 22–36 h and 90-day mortality. Results: Overall, 780 patients had available baseline data on prior APT. Compared with the no prior APT group (n = 523), the prior APT group (n = 257) was older (72 vs. 66 years) and had a higher prevalence of vascular risk factors. There was no interaction between prior APT and treatment effects of alteplase (p for interaction = 0.23). In the prior APT patients, 55/125 (45%) patients in the alteplase group and 39/132 (30%) patients in the control group had a favorable outcome (adjusted odds ratio [aOR], 2.07 [95% confidence interval, 1.18–3.64]). The rates of sICH and mortality in the alteplase and control groups were 5.6% and 0.8% (aOR, 7.78 [0.94–63.37]) and 6.5% and 6.1% (aOR, 1.12 [0.38–3.36]), respectively. In the no prior APT patients, 136 patients (50%) in the alteplase group and 112 patients (45%) in the control group had a favorable outcome (aOR, 1.39 [0.94–2.05]). Safety outcomes were not significantly different between the groups (sICH: 3 [1.1%] vs. 1 [0.4%]; mortality: 13 [4.9%] vs. 3 [1.2%]). Conclusions: Alteplase has consistent efficacy regardless of prior APT in patients with unknown onset stroke. In addition, prior APT does not significantly increase the risk of sICH or mortality.