INTRODUCTION:Recent randomised trials have questioned the benefit of endovascular therapy (EVT) for MeVO stroke, but data from clinical practice are limited. This study aimed to assess the effectiveness and safety of EVT, with or without intravenous thrombolysis (IVT), vs IVT alone in MeVO stroke using registry-based real-world data. PATIENTS AND METHODS:This retrospective multicentre study included patients from 82 Italian centres in the Safe Implementation of Treatments in Stroke (SITS) registry (January 2020-December 2023). Adults with acute ischaemic stroke due to MeVO (ACA A1/A2, MCA M2/M3 or more distal or PCA P1/P2), treated with IVT or EVT ± IVT, and with available 90-day mRS scores were included. Patients with tandem occlusions were excluded. Propensity score matching (1:1) was used to balance baseline variables. Primary outcome was functional independence (mRS 0-2) at 90 days. Secondary outcomes included in-hospital mortality, intracranial haemorrhage incidence and recanalisation status. RESULTS:Among 1375 total patients, 780 were included and matched (390 per group) by propensity score. Baseline characteristics were balanced. Functional independence at 90 days was achieved in 60.6% of EVT ± IVT patients vs 60.9% in the IVT-only group (odds ratio [OR] 0.99; 95% CI, 0.73-1.34; P = .939). When restricted to patients with baseline mRS < 2, functional independence rates remained comparable between groups, confirming the primary findings. In-hospital mortality was non-significantly lower in the EVT ± IVT group (5.4% vs 8.7%, P = .069). Symptomatic intracranial haemorrhage rates were comparable between groups, although overall haemorrhagic complications were higher with EVT (18.4% vs 11.2%, P < .0001). Stratified analyses by stroke severity and treatment timing showed consistent lack of benefit across all subgroups (all interaction P-values > .05). DISCUSSION:The absence of functional benefit from EVT observed in this real-world cohort is consistent with the results of the ESCAPE-MeVO and DISTAL randomized trials. Notably, the higher rate of any intracranial haemorrhage in the EVT group (18.4% vs 11.2%), driven primarily by minor haemorrhagic events, represents a clinically meaningful safety concern that must be weighed against the lack of demonstrated efficacy. A hypothesis-generating signal was observed in patients treated within 180 minutes (OR 2.16, 95% CI 1.06-4.38), warranting prospective investigation. The retrospective design and the limitations inherent to registry-based data, including incomplete procedural data and anatomical heterogeneity in MeVO classification, should be considered when interpreting these findings. CONCLUSIONS:Endovascular therapy did not improve long-term functional outcomes compared to IVT alone in MeVO stroke but was associated with higher haemorrhagic risk. These findings support a cautious approach to EVT in this setting, in line with recent trial evidence.

BACKGROUND AND OBJECTIVES:Contrast-associated acute kidney injury (CA-AKI) is a potentially preventable complication after exposure to iodinated contrast media. In patients undergoing endovascular thrombectomy (EVT) for acute ischemic stroke (AIS), the incidence and clinical impact are poorly characterized, and no validated prediction tool is currently available. The aim of this study was to assess the incidence and prognostic significance of CA-AKI in EVT-treated patients with AIS and to develop and validate a predictive score. METHODS:A retrospective, multicenter cohort study was conducted involving EVT-treated patients across 73 centers in 16 countries (January-December 2023). Inclusion criteria were age ≥18 years, absence of dialysis, availability of preprocedural and 48-hour postprocedural creatinine levels, and available 90-day follow-up (modified Rankin Scale [mRS] score). The primary outcome was CA-AKI, defined by KDIGO (Kidney Disease: Improving Global Outcomes criteria;creatinine increase ≥0.3 mg/dL or ≥1.5 times baseline, within 48 hours). Secondary outcomes were (1) in-hospital mortality, (2) 90-day mRS score, and (3) 90-day severe disability or death (mRS score >3). Logistic models assessing associations with outcomes accounted for within-center clustering by applying robust standard errors. CA-AKI prediction models were developed across imputed data sets using univariable selection (p < 0.20), backward elimination (p < 0.05), and coefficient-based scoring after categorization of continuous predictors, with internal validation by bootstrap to obtain optimism-adjusted estimates. RESULTS:Among 6,638 patients (median age 74 years; 48.7% male), CA-AKI occurred in 326 (4.9%) and was independently associated with in-hospital mortality (adjusted odds ratio [aOR] 2.269; 95% CI 1.615-3.190), higher 90-day mRS scores (adjusted common odds ratio 1.584; 95% CI 1.110-2.258), and 90-day severe disability or death (aOR 1.530; 95% CI 1.057-2.216). A preprocedural risk model including 12 routine clinical variables-sex, ethnicity, arterial hypertension, dyslipidemia, chronic kidney disease, antiplatelet therapy, NIH Stroke Scale score at admission, serum glucose, estimated glomerular filtration rate, hemoglobin, mean arterial pressure, and IV thrombolysis-demonstrated acceptable discrimination (area under the receiver operating characteristic curve 0.710 [95% CI 0.682-0.738]; precision-recall area under the curve 0.13 [95% CI 0.10-0.16]), good calibration (slope 0.870 [95% CI 0.759-0.928]), good overall performance (Brier score 0.045 [95% CI 0.042-0.049]). A second model that included EVT-related variables (e.g., contrast volume) showed similar performances. DISCUSSION:In this large, international cohort, CA-AKI occurred in approximately 1 in 20 EVT-treated patients with AIS and was independently associated with poor outcomes. A simple preprocedural risk score enables early identification of high-risk individuals and may support preventive strategies.

BACKGROUND:Nearly half of the patients who received endovascular thrombectomy (EVT) for large vessel occlusion experience poor functional outcomes. Reliable tools for early post-procedural prognostication are needed. We aimed to assess and compare the performance of existing, pragmatic post-EVT prognostic scores in a large national multicenter cohort. METHODS:We conducted a systematic literature search to identify pragmatic post-thrombectomy prognostic scores predicting 90-day functional outcomes. Models relying on advanced imaging, small derivation samples, or machine learning were excluded. We analyzed data from the IRETAS registry-a prospective, multicenter Italian cohort of stroke patients treated with EVT. Inclusion criteria were pre-stroke modified Rankin Scale (mRS) ⩽ 2 and available 90-day mRS. The primary outcome was good functional outcome (mRS ⩽ 2). Prognostic performance was assessed using c-statistics in the samples where each individual score was measurable. Scores were compared using DeLong tests in the subset of patients for whom all scores were measurable. RESULTS:Three scores were identified: HERMES-24, BET, and SNARL. Among 22,768 patients in the registry, 18,408 (89.1%) had a measurable HERMES-24 score, 13,593 (59.7%) had a measurable BET score, and 19,007 (83.5%) had a measurable SNARL score. Median age was 75 years (IQR 65-82), and 11,528 (50.6%) were female. In the subset in which each test was measurable, HERMES-24 showed the best performance for predicting mRS ⩽ 2 (c-statistic = 0.889), followed by BET (c-statistic = 0.794) and SNARL (c-statistic = 0.762) (p < 0.001). In the subset of 12,233 patients for whom all three prognostic scores were calculable, a head-to-head comparison confirmed the superior performance of the HERMES-24 model: HERMES-24 score versus BET score (c-statistic difference = 0.098 [95% CI = 0.092-0.105]; p < 0.001) and HERMES-24 score versus SNARL score (c-statistic difference = 0.124 [95% CI = 0.116-0.132]; p < 0.001). CONCLUSIONS:In this large, multicenter, national cohort, the post-EVT HERMES-24 score-which accounts only for age and 24-h NIHSS-demonstrated the highest prognostic performance among existing, pragmatic post-EVT scores. Its simplicity and robust performance support its routine adoption in clinical practice.

BACKGROUND:In the early time window, direct mechanical thrombectomy (MT) is not non-inferior to combined treatment with intravenous thrombolysis (IVT) for patients with large vessel occlusion (LVO) stroke, while its non-inferiority in the extended time window remains uncertain. This study assessed whether direct MT is non-inferior to IVT + MT beyond 4.5 h or at wake-up. METHODS:We emulated a non-inferiority trial, comparing direct MT vs. IVT + MT, including patients with anterior circulation LVO between 4.5 and 24 h from symptom onset or at wake-up, without contraindications to IVT and with target perfusion mismatch. We used inverse probability weighting (IPW) adjusted for pre-specified covariates. The primary outcome was 90-day mRS 0-2, with non-inferiority defined by a lower 95% CI boundary of the Risk Difference (RD) ≥ -1.3%. RESULTS:Among 347 patients, 212 received direct MT and 135 received IVT + MT. After IPW, patients treated with direct MT and IVT + MT had a similar likelihood of achieving a 90-day mRS of 0-2 (adjRD -2.90 [95% CI -6.64 to 0.84]) with the lower boundary of the RD 95% CI crossing the non-inferiority margin. Additionally, direct MT was associated with a shift toward a higher score on the 90-day mRS (adjusted Common OR 1.59 [95% CI 1.05-2.39]), not confirmed after IPW, and with lower odds of successful recanalization (adjOR 0.38 [95% CI 0.18-0.78]). Rates of 90-day mRS 0-1, sICH, and mortality were similar between groups. CONCLUSIONS:In our target trial emulation, direct MT was not non-inferior to IVT + MT treatment beyond 4.5 h from symptom onset or at wake-up, with IVT before MT yielding higher successful recanalization rates.

Introduction Infarct growth rate (IGR) is highly heterogeneous among ischemic stroke patients, reflecting a spectrum of progressor phenotypes with clinical implications. We aim to compare different imaging approaches to investigate stroke progressors phenotypes and their clinical implications in patients undergoing thrombectomy. Methods Data are from the prospective Italian Registry of Endovascular Treatment in Acute Stroke (IRETAS). Patients with M1/M2 occlusion and known symptom onset were included. Progressor phenotypes were defined using (1) NCCT-based definitions (ASPECTS points decay per hour < 0.25 pts/h=slow progressor, 0.25-0.50 pts/h=intermediate, and > 0.50 pts/h=fast); and (2) CTP-based definitions (CTP-estimated core divided by time of onset < 5 mL/h=slow progressors, 5-10mL/h=intermediate, and > 10 mL/h=fast). The primary outcome was 90-day good functional outcome (modified Rankin Scale [mRS] = 0-2). Associations were assessed with logistic regression analyses adjusted for age, sex, NIHSS, TICI score, thrombolysis, and imaging-to-recanalization time. Results Of 26799 patients screened, 8322 (31.1%) were included (NCCT group: 8076; CTP group: 897 patients). NCCT-based progressor phenotype was associated with lower odds of good outcome (aOR 0.82 [95%CI = 0.72-0.92] per each progressor phenotype increase). ASPECTS decay per hour was associated with lower odds of good outcome (acOR 0.94 [95%CI = 0.89-0.99]). No significant association was observed for either CTP-based progressor phenotype or CTP-based IGR (mL/h). Similar findings were observed for secondary outcomes. Conclusions In this large, real-world cohort of stroke patients, NCCT-based IGR was associated with functional outcomes, whereas CTP-based IGR was not. This highlights the need to refine and identify more accurate markers of infarct growth within perfusion imaging.

Background: Recent randomized trials have questioned the benefit of endovascular therapy (EVT) for medium vessel occlusion (MeVO) stroke, but data from clinical practice are limited. This study aimed to assess the effectiveness and safety of EVT, with or without intravenous thrombolysis (IVT), versus IVT alone in MeVO stroke using registry-based real-world data. Methods: This retrospective multicenter study included patients from 76 Italian centers in the SITS registry (January 2020-December 2023). Adults with acute ischemic stroke due to MeVO (ACA A1/A2, MCA M2/M3 or more distal, or PCA P1/P2), treated with IVT or EVT±IVT, and with available 90-day modified Rankin Scale (mRS) scores were included. Patients with tandem occlusions were excluded. Propensity score matching (1:1) was used to balance baseline variables. Primary outcome was functional independence (mRS 0-2) at 90 days. Secondary outcomes included in-hospital mortality, intracranial hemorrhage incidence, and recanalization status. Results: Among 1375 total patients, 780 were included and matched (390 per group) by propensity score. Baseline characteristics were balanced. Functional independence at 90 days was achieved in 57.7% of EVT±IVT patients versus 59.2% in the IVT-only group (OR 0.939, 95% CI 0.706-1.248, p=0.663). In-hospital mortality was non significantly lower in the EVT±IVT group (5.4% vs 8.7%, p=0.069). Symptomatic intracranial hemorrhage rates were comparable between groups, although overall hemorrhagic complications were higher with EVT (18.4% vs 11.2%, p<0.0001). Successful recanalization occurred in 81.0% of EVT cases. Stratified analyses by stroke severity and treatment timing showed consistent lack of benefit across all subgroups (all interaction p-values >0.05). Conclusions: EVT did not improve long-term functional outcomes compared to IVT alone in MeVO stroke but was associated with higher hemorrhagic risk. These findings support a cautious approach to EVT in this setting, in line with recent trial evidence. ### Competing Interest Statement AZ declares consulting and speaker fees from Bayer, Boehringer-Ingelheim, Alexion, Daiichi Sankyo, Pfizer, PIAM, Amgen, fees for Advisory Board from Boehringer-Ingelheim, Daiichi Sankyo, Bayer and Astra Zeneca, not related to this study. ### Funding Statement This research received no specific grant from any funding agency in the public, commercial, or not-for-profit sectors. ### Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes The details of the IRB/oversight body that provided approval or exemption for the research described are given below: The coordinating center (Fondazione IRCCS San Gerardo dei Tintori, Monza) determined that this study is exempt from full review as it involves secondary analysis of de-identified data from the SITS registry. Participating sites confirmed that no additional local approval was required for use of de-identified registry data, per local regulations. Informed consent was [waived/not required] due to use of de-identified data. I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines, such as any relevant EQUATOR Network research reporting checklist(s) and other pertinent material, if applicable. Yes The data are available from the SITS registry but restrictions apply to the availability of these data, which were used under license for the current study, and so are not publicly available. Data are however available from the authors upon reasonable request and with permission of the SITS registry.

Importance:Early treatment choice in relapsing-remitting multiple sclerosis (RRMS) is prognostically crucial, yet robust comparative data on cladribine vs sphingosine-1-phosphate receptor modulators (S1PRMs) in treatment-naive patients with RRMS are limited. Objective:To compare the clinical effectiveness of cladribine vs S1PRMs in treatment-naive individuals with RRMS. Design, Setting, and Participants:This comparative effectiveness research study used data from 108 Italian multiple sclerosis (MS) centers affiliated with the Italian Multiple Sclerosis and Related Disorders Register. All treatment-naive patients with RRMS who initiated cladribine or an S1PRM (fingolimod, ozanimod, or ponesimod) between January 2011 and October 2021 and had at least 12 months of follow-up were included. Propensity score matching and pairwise censoring were used to balance baseline differences and follow-up duration. Patient data were extracted from the register in September 2024. Exposure:Initiation of cladribine or an S1PRM, with duration reflecting clinical practice. Main Outcomes and Measures:The primary outcome was no evidence of disease activity (NEDA-3) and its subcomponents. Secondary analyses evaluated disability accrual subdivided into progression independent of relapse activity (PIRA) and relapse-associated worsening (RAW), plus variables associated with treatment response. Cox proportional hazards models, adjusted for visit and magnetic resonance imaging (MRI) frequency, were used to compare outcomes. Results:Of the 1587 patients (485 taking cladribine and 1102 taking S1PRMs), matching yielded 475 pairs (950 individuals; mean [SD] age, 34.7 [10.7] years; 686 female [72.2%]), with a median (IQR) follow-up period of 25 (12-60) months. For the cladribine vs S1PRM groups, no significant differences were observed in relapse rates (72 patients [15.2%] vs 76 patients [16.0%]), MRI activity (137 patients [31.3%] vs 145 patients [34.8%]), or NEDA-3 loss (194 patients [44.4% vs 219 patients [52.2%]). Cladribine was associated with a lower risk of disability worsening vs S1PRM (54 patients [11.4%] vs 70 patients [14.7%]; hazard ratio [HR], 0.64; 95% CI, 0.42-0.96; P = .03), a finding that was confirmed in sensitivity analyses for patients younger than 40 years, those whose diagnoses were made according to the 2017 McDonald Criteria, and those with Expanded Disability Status Scale score less than or equal to 3.0. This was mainly driven by reduced PIRA risk with cladribine (HR, 0.40; 95% CI, 0.20-0.79; P = .009), with no RAW difference. After 36 months, patients treated with cladribine showed higher relapse risk (HR, 1.81; 95% CI, 1.02-3.20; P = .04) and increased NEDA-3 loss (HR, 2.08; 95% CI, 1.18-3.67; P = .01). Discontinuation rates were similar (HR, 0.92; 95% CI, 0.67-1.15; P = .58). Conclusions and Relevance:These findings suggest cladribine was associated with superior effectiveness in reducing disability progression over 25 months, likely due to reduced PIRA, despite comparable short-term NEDA-3 outcomes. However, relapse prevention declined after 36 months, suggesting retreatment or therapy modification within 3 years may be needed to maintain long-term disease control.

The benefits and safety of mechanical thrombectomy (MT) in patients with prestroke disability, classified as modified Rankin Scale (mRS) score of 3 to 4, and anterior circulation stroke remain uncertain. This study aims to evaluate these factors using data from the Italian Registry of Endovascular Treatment in Acute Stroke. We analyzed data collected between 2015 and 2021, comparing functional outcomes (mRS), symptomatic intracerebral hemorrhage, and recanalization rates (Thrombolysis in Cerebral Infarction) at 90 days post-MT in patients with prestroke mRS score of 3 to 4 versus 0 to 2. A good outcome was defined as no change in the mRS score from baseline. Subgroup analysis was stratified by age. A total of 11.411 (96%) patients with prestroke mRS score of 0 to 2 and 477 (4%) patients with prestroke mRS score of 3 to 4 were included. Compared with patients with a baseline mRS score 0 to 2, those with mRS score 3 to 4 were older (82 versus 75 years; P<0.001) and predominantly female (71.7% versus 53%; P<0.001). The maintenance of the same mRS score after MT was observed in 100 (23.3%) patients with prestroke mRS score 3 to 4, compared with 2332 (22.1%) patients with mRS score 0 to 2 (P=0.556). Mortality was significantly higher in the mRS score 3 to 4 group (n=159 [37.1%] versus n=1939 [18.4%]; P<0.001). Successful recanalization (Thrombolysis in Cerebral Infarction score ≥2b) was lower in the mRS score 3 to 4 group (n=333 [71.6%] versus n=8706 [77.7%]; P=0.002), while no significant differences in symptomatic intracerebral hemorrhage were found. The benefit of MT was maintained in patients aged 80 to 85 and over 85 years with prestroke mRS score 3 to 4, although mortality remained higher. Our data suggest that prestroke disability does not imply less chance of returning to prestroke conditions after MT, even in octogenarians, despite higher mortality and lower recanalization rate. More data are warranted to better understand the benefit of MT in this subgroup of patients.

BACKGROUND AND PURPOSE:Understanding the causes of recurrent ischemic events in patients with minor stroke or high-risk TIA is crucial to understand unmet needs in secondary prevention. This study examines the characteristics and causes of recurrences after non-cardioembolic minor stroke/high-risk TIA in patients treated with the best medical care. METHODS:This subgroup analysis from a prospective real-world study (READAPT, NCT05476081) included patients with non-cardioembolic minor ischemic stroke (NIHSS ≤5) or TIA (ABCD2 score ≥ 4), receiving short-term DAPT. We described the etiologic distribution according to the Trial of ORG 10172 in Acute Stroke Treatment (TOAST) classification of the index and of the recurrent event. We analyzed baseline characteristics of patients with and without a 90-day ischemic recurrence to identify factors linked to recurrence. RESULTS:Out of 1641 patients, 56 (3.4 %) had a recurrent ischemic event (35 strokes and 21 TIAs). The cause of recurrences was undetermined in 21 (37.5 %), small vessel occlusion in 18 (32.1 %), large artery atherosclerosis in 11 (19.6 %), other determined in 3 (5.4 %), and cardioembolism in 3 (5.4 %). The etiologic distribution of recurrent events differed from that of the corresponding index events (p = 0.002). Non-compliance to DAPT was more prevalent in patients with recurrences compared with those without (8.9 % vs 3.7 %, p = 0.048). CONCLUSIONS:Patients with recurrences after a minor stroke or high-risk TIA have a different etiologic distribution compared with their index events. Additionally, a lower compliance to DAPT was observed in those with recurrences, suggesting that adherence to DAPT should be encouraged to optimize the outcome of patients.

The impact of stroke etiology on outcomes in patients who underwent endovascular thrombectomy (EVT) is still a matter of debate. We studied the effect of aterosclerotic versus cardioembolic etiology on the clinical and radiological outcome of patients with stroke due to large vessel occlusion (LVO) treated with EVT on a large sample of stroke patients enrolled in a nationwide registry. The source of data was the Italian Registry of Endovascular Stroke Treatments, a national, prospective, observational internet-based registry including patients treated with EVT since 2011. We extracted and compared data of patients suffering from large atherosclerosis (LAA) or cardioembolic (CE) stroke. We included 5193 patients, 3899 CE, and 1294 LAA stroke. Patients with CE were significantly older (p < 0.001), and their stroke severity at admission was significantly higher (p < 0.001). Moreover, patients with LAA had significantly longer onset to end of procedure time, and procedure duration than CE patients. Good outcome at three months was reported in 45.2

BACKGROUND AND AIM:According to randomized controlled trials (RCTs), dual antiplatelet therapy (DAPT) is more effective for secondary prevention of ischemic events attributable to large artery atherosclerosis (LAA) than other mechanisms. We investigated whether real-world application may impact DAPT effectiveness and safety in the REAl-life study on short-term Dual Antiplatelet treatment in Patients with ischemic stroke or Transient ischemic attack (READAPT, NCT05476081). METHODS:READAPT was an observational multicenter study including patients with minor ischemic stroke or TIA treated with short-term DAPT. At 90 days, we assessed primary effectiveness (ischemic recurrence, severe bleeding, or vascular death) and safety (severe to moderate bleeding) outcomes. We explored associations between LAA and outcomes using Cox regression. Within patients with and without LAA, outcomes were compared between subgroups based on age, NIHSS score (for ischemic stroke patients), ABCD2 score (for TIA patients), presence and number of MRI acute lesions, and DAPT regimen characteristics. RESULTS:Among 1920 analyzed patients (of 2278 enrolled), 452 had LAA. Unlike RCTs, 21.2% of patients with LAA had NIHSS > 5, and 48.2% received DAPT > 30 days. Patients with LAA had higher bleeding rates (3.5% vs. 2.1%, p = 0.004), primarily hemorrhagic infarctions and moderate bleeding, than those without LAA. However, primary effectiveness outcomes were similar (4.9% vs. 3.5%, p = 0.201) between the groups. In patients with LAA, prolonged DAPT (> 21 days), multiple MRI lesions, age ≥ 65, and loading doses increased bleeding risk. CONCLUSIONS:The real-world DAPT use in patients with LAA exceeds RCTs boundaries with possible drawbacks on treatment safety.

Background: Dual antiplatelet therapy (DAPT) is a cornerstone of secondary prevention in patients with minor ischemic stroke or high-risk transient ischemic attack. The effectiveness and safety of DAPT may differ between patients with posterior (PCI) and anterior circulation infarct (ACI). Objectives: We aimed to compare short-term outcomes following DAPT between mild-to-moderate stroke patients with PCI versus ACI. Design: Propensity-matched analysis from a prospective real-world multicentric cohort study (READAPT). Methods: We included patients with noncardioembolic mild-to-moderate stroke (National Institute of Health Stroke Scale of 0–10) who initiated DAPT within 48 h of symptom onset. Patients were categorized into ACI or PCI based on the infarct(s) location on brain neuroimaging. The primary effectiveness outcome was the 90-day risk of ischemic stroke or other vascular events. The secondary effectiveness outcomes were the 90-day modified Rankin Scale (mRS) score distribution, 24-h early neurological improvement or deterioration, and all-cause mortality. The safety outcomes included the 90-day risk of any bleedings and 24-h hemorrhagic transformation. Results: We matched 281 PCI patients with 651 ACI patients. The 90-day risk of ischemic stroke or other vascular events was low and similar between PCI and ACI groups (3.1% vs 2.9%, respectively; hazard ratio 0.98, (95% confidence interval (CI) 0.45–2.14); p = 0.845). Patients with PCI had worse 90-day mRS ordinal distribution compared to those with ACI (odds ratio 1.18 (95% CI 1.01–1.39); p = 0.046). There were no differences in other secondary outcomes. Safety outcomes had low incidence and did not differ between groups (any bleedings: 3.2% vs 2.6%; 24-h hemorrhagic transformation: 1.8% vs 1.2%). We found no differences in the risk of ischemic stroke or other vascular events between patients with PCI and ACI across subgroups defined by sex, age, presumed stroke etiology, stroke severity, prestroke mRS, hypertension, diabetes, acute reperfusion therapies, DAPT loading dose, or presence of symptomatic intracranial stenosis. Conclusion: Our findings suggest that effectiveness and safety outcomes after DAPT in patients with mild-to-moderate noncardioembolic ischemic stroke are consistent regardless of infarct location in the anterior or posterior circulation territory. However, patients with PCI may experience worse short-term functional outcome. Trial registration: URL: www.clinicaltrials.gov ; Unique identifier: NCT05476081.

Current data regarding the effect of intravenous thrombolysis (IVT) in patients with acute ischaemic stroke (AIS) with concomitant malignancy remain unclear. This study aimed to evaluate the efficacy and safety of IVT in patients with AIS and concomitant active cancer. The ITACA-stroke study was a retrospective observational study based on prospective registries of a multicentre international collaboration. Patients with a diagnosis of active cancer and AIS, treated or not with IVT, were enrolled. Multivariable logistic regression analysis was performed to identify independent predictors for functional outcomes (mortality and good functional outcome) and haemorrhagic events at 90 days. A propensity score matching (PSM) analysis compared IVT and no-IVT patients. A total of 521 patients were included, 225 were treated with IVT and 296 were not treated with IVT. IVT was directly correlated with good functional outcome (OR: 2.56, 95

INTRODUCTION:Patients with ischemic stroke or transient ischemic attack (TIA) and cancer face unique risks of recurrent ischemic events and bleeding. It is unclear whether this increased risk is present even in patients with minor ischemic stroke or transient ischemic attack (TIA) receiving dual antiplatelet therapy (DAPT). This study aimed to evaluate the impact of cancer on the short-term outcomes after DAPT in patients with non-cardioembolic minor ischemic stroke or high-risk TIA. PATIENTS AND METHODS:This was a secondary analysis of the prospective multicentric READAPT study (NCT05476081), including patients with non-cardioembolic minor ischemic stroke (NIHSS ⩽ 5) or high-risk TIA (ABCD2 ⩾4) who initiated DAPT within 48 h of symptom onset. The primary effectiveness outcome was the 90-day risk of new ischemic stroke or other vascular events (TIA, myocardial infarction, death due to vascular causes). Secondary outcomes included 90-day mRS score distribution and all-cause mortality. The primary safety outcome was the 90-day risk of any bleeding, with secondary safety outcomes including 24-h hemorrhagic transformation. We used Inverse Probability Weighting to compare outcomes between patients with and without cancer. RESULTS:From 2278 patients in the READAPT study cohort, we included 1561 patients (mean age 70.3 ± 11.7 years; 65.4% males), of whom 206 (13.2%) had cancer, categorized as either active (27.7%) or in remission (72.3%). After weighting, overall cancer patients had a higher risk of 90-day new ischemic stroke or other vascular events (weighted HR 1.78, 95% CI 1.20-2.63, p = 0.004) and worse 90-day mRS score distribution (OR 1.24, 95% CI 1.10-1.41, p < 0.001) compared to patients without cancer. The 90-day risk of bleeding did not differ between cancer and no-cancer groups overall. When analyzing cancer subgroups, patients with active cancer had significantly higher risk of 90-day ischemic stroke or other vascular (weighted HR 2.75, 95% CI 1.70-4.45, p < 0.001) and any bleeding (weighted HR 2.51, 95% CI 1.27-4.97, p = 0.008) events compared to no-cancer patients. In contrast, patients with cancer in remission had comparable risks to those without cancer. Furthermore, hematological malignancies were associated with a substantially higher risk of 90-day new ischemic stroke or other vascular events compared to solid tumors (weighted HR 8.15, 95% CI 5.06-13.14, p < 0.001). CONCLUSIONS:Patients with minor ischemic stroke or high-risk TIA and active cancer have increased risk of ischemic and bleeding events after DAPT. Conversely, patients with cancer in remission have similar outcomes compared to those with no cancer.

Background:Elevated baseline systolic blood pressure (SBP) was associated with poor outcomes following dual antiplatelet therapy (DAPT) in patients with non-cardioembolic minor ischemic stroke (MIS) or high-risk transient ischemic attack (TIA) in clinical trials. Objectives:We aimed to assess the impact of admission SBP on the short-term outcomes after DAPT in patients with non-cardioembolic MIS or high-risk TIA. Methods:We performed an inverse probability weighted (IPW) analysis from a prospective multicentric real-world study (READAPT) including patients with non-cardioembolic MIS (National Institute of Health Stroke Scale of 0-5) or high-risk TIA (ABCD2 ⩾4) who initiated DAPT within 48 h of symptom onset. The primary effectiveness outcome was the 90-day risk of new ischemic stroke or other vascular events. The secondary effectiveness outcomes were the 90-day modified Rankin Scale score ordinal shift, vascular and all-cause mortality, 24-h early neurological improvement or deterioration. The safety outcomes included the 90-day risk of moderate-to-severe and any bleedings, symptomatic intracranial hemorrhage, and 24-h hemorrhagic transformation. We used Cox proportional hazards regression with restricted cubic splines to model the continuous relationship between SBP and the hazard ratio (HR) of new vascular events. We selected SBP = 124 mm Hg as cut-off point for the IPW weighting. Outcomes were compared using Cox and generalized logistic regression analyses, adjusted for residual confounders. Results:From 2278 patients in the READAPT cohort, we included 1291 MIS or high-risk TIAs (mean age 70.6 ± 11.4 years; 65.8% males). After IPW, patients with admission SBP ⩾124 mm Hg versus <124 mm Hg had a significantly higher risk of 90-day ischemic stroke or other vascular events (adjusted HR: 2.14 (95% CI 1.07%-4.98%); p = 0.033) and of 24-h early neurological deterioration (adjusted risk difference: 1.91% (95% CI 0.60%-3.41%); p = 0.006). The overall risk of safety outcomes was low, although patients with SBP ⩾124 mm Hg on admission showed higher rates of 90-day moderate-to-severe and any bleeding events (adjusted risk difference: 1.24% (95% CI 0.38%-2.14%); p = 0.004 and 6.18% (95% CI 4.19%-8.16%); p < 0.001; respectively), as well as of 24-h hemorrhagic transformation (adjusted risk difference: 1.57% (95% CI 0.60%-2.55%); p = 0.001). Subgroup analysis showed a significant interaction between admission SBP, sex, and time to DAPT start in predicting 90-day new vascular events (p for interaction <0.001 and 0.007, respectively). Conclusion:In patients with non-cardioembolic MIS or high-risk TIA, higher levels of admission SBP may be associated with an increased risk of new vascular events, early neurological deterioration, and bleeding after DAPT use. Future studies should further investigate if optimizing blood pressure management may further improve prognosis.

Mechanical thrombectomy (MT) was found to be beneficial in acute ischemic stroke patients with anterior tandem occlusion (a-TO). Instead, little is known about the effectiveness of MT in stroke patients with posterior tandem occlusion (p-TO). We aimed to compare MT within 24 h from last known well time in ischemic stroke patients with p-TO versus a-TO. We conducted a cohort study on prospectively collected data of patients registered in the Italian Registry of Endovascular Treatment in Acute Stroke (IRETAS) who were treated with MT within 24 h from last known well time for acute ischemic stroke with p-TO (n = 275) or a-TO (n = 1853). After adjustment for unbalanced pre-procedure variables (year 2015–2021, age, sex, NIHSS score, ASPECTS, and time strata for puncture groin) and pre-stroke mRS score as pre-defined predictor, p-TO was significantly associated with lower probability of mRS score 0–2 (OR 0.415, 95

BACKGROUND:The outcomes of minor ischemic stroke resulting from small artery occlusion (SAO-MIS) have not yet been characterized after dual antiplatelet treatment (DAPT) has become the standard of care. We provided updated figures on the short-term prognosis of SAO-MIS treated with early short-term DAPT and compared the outcomes of SAO-MIS versus non-SAO-MIS patients. METHODS:This is a prespecified sub-analysis from a prospective multicentric real-world study (READAPT, NCT05476081) including patients with minor (NIHSS≤5) non-cardioembolic ischemic stroke treated with DAPT. The primary outcome was a composite of 90-day symptomatic ischemic stroke or major cardiovascular events. Secondary outcomes were the 90-day ordinal distribution of modified Rankin Scale (mRS) scores, 90-day excellent functional outcome (mRS of 0 to 1), and 24-h early neurological deterioration (END). Safety outcomes were 90-day intracerebral hemorrhage, moderate-to-severe and any bleedings. All outcomes were compared between SAO-MIS and non-SAO-MIS patients. RESULTS:We included 678 MIS, of whom 253 (37.3 %) were SAO-related. At 90 days, 3 patients with SAO-MIS had primary outcome (1.2 % [95 % CI 0.2 %-3.5 %]), which were all SAO-related ischemic strokes. For the secondary outcomes, most SAO-MIS patients (n = 191, 75.5 %) had 90-day excellent functional outcome and 12 had 24-h END (4.7 % [95 % CI 2.5 %-8.3 %]). Referring to safety outcomes, 90-day intracerebral hemorrhage occurred only in one patient with SAO-MIS (0.4 % [95 % CI 0.0 %- 2.2 %]). Compared to non-SAO-MIS, the 90-day risk of recurrent vascular events was significantly lower among SAO-MIS (aHR 0.24 [95 % CI 0.08-0.68]; p = 0.007), while there were not significant differences in other secondary outcomes, nor in the risk of safety events. CONCLUSIONS:Our findings show overall favorable short-term prognosis after SAO-MIS treated with DAPT. Future studies should investigate factors associated with residual stroke risk and long-term outcomes of SAO-MIS.

BACKGROUND:Short-term dual antiplatelet treatment (DAPT) is superior to single antiplatelet treatment (SAPT) for secondary prevention in non-cardioembolic minor ischemic stroke and high-risk transient ischemic attack (TIA). As the real-world use of DAPT is broader than in trials, it is important to clarify its benefit/risk profile in a diverse population. METHODS:Post hoc analysis of prospectively collected data from the READAPT cohort and three prospective stroke registries including patients with mild-to-moderate (National Institute of Health Stroke Scale (NIHSS) score 0-10) ischemic stroke receiving early DAPT or SAPT. The primary effectiveness outcome was 90-day return to pre-stroke neurological functioning using modified Rankin Scale (mRS) score. Secondary effectiveness outcomes were 90-day mRS shift, new ischemic stroke/TIA, vascular and all-cause death, 24 h early neurological improvement or deterioration. The safety outcome was 90-day intracranial hemorrhage. RESULTS:We matched 1008 patients treated with DAPT and 1008 treated with SAPT. Compared to SAPT, patients treated with DAPT showed higher likelihood of 90-day primary effectiveness outcome (87.5% vs. 84.4%, risk difference 3.1% (95% confidence interval (CI): 0.1%-6.1%); p = 0.047, risk ratio 1.03 (95% CI: 1.01-1.07); p = 0.043) and higher rate of 24-h early neurological improvement (25.3% vs. 15.4%, risk difference 9.9% (95% CI: 6.4%-13.4%); p < 0.001, risk ratio 1.65 (95% CI: 1.37-1.97); p < 0.001). No differences were observed for other study outcomes. Subgroup analysis confirmed benefit of DAPT over SAPT for primary effectiveness outcome in patients with moderate stroke, those treated with intravenous thrombolysis, and those who received antiplatelet loading dose. CONCLUSION:Our findings suggest that DAPT use might be safe and more effective than SAPT even in the real world and in patients who do not strictly fulfill the criteria of landmark large clinical trials.

BACKGROUND:According to the literature, about one third of patients with brain ischemic symptoms lasting <24 h, which are classified as Transient ischemic attacks (TIAs) according to the traditional "time-based" definition, show the presence of acute ischemic lesions at neuroimaging. Recent evidence has shown that the presence of acute ischemic lesions at neuroimaging may impact on the outcome of patients with transient ischemic symptoms treated with dual antiplatelet treatment (DAPT). This uncertainty is even more compelling in recent years as short-term DAPT has become the standard treatment for any non-cardioembolic TIA or minor ischemic stroke. METHODS:This is a pre-specified subgroup analysis from a prospective multicenter real-world study (READAPT). The analysis included patients with time-based TIA-that is, those with ischemic symptoms lasting <24 h-who started DAPT. In the whole population, we assessed the presence of acute brain ischemic lesions at neuroimaging and their association with the ABCD2 score. To assess the impact of acute brain ischemic lesions on 90-day prognosis, we performed a propensity score matching of patients with and without those lesions. We adopted a primary effectiveness outcome which was a composite of new stroke/TIA events and death due to vascular causes at 90 days. RESULTS:We included 517 patients-324 (62.7%) male-with a median (interquartile range-IQR) age of 74 (IQR = 65-81) years; 144 patients (27.9%) had acute brain ischemic lesions at neuroimaging. The proportion of patients with brain ischemic lesions did not vary according to the ABCD2 score. At follow-up, 4 patients with brain ischemic lesions (2.8%) and 21 patients without lesions (5.6%) reported the primary effectiveness outcome, which was similar between the groups before (p = 0.178) and after matching (p = 0.518). CONCLUSIONS:In our population, patients with transient ischemic symptoms and acute ischemic lesions at brain magnetic resonance imaging (MRI) had a risk of recurrent ischemic events similar to those without lesions. The risk of recurrent ischemic events was low in both groups.