BACKGROUND:Despite successful reperfusion after endovascular therapy (EVT), over 50% of patients with large vessel occlusion (LVO) and large core infarction fail to achieve favorable functional outcomes, termed 'futile recanalization'. This study aimed to identify predictors and develop a scoring system to predict futile recanalization in patients with LVO and large core infarction undergoing EVT. METHODS:Patients were selected from the Acute Anterior Circulation Large Vessel Occlusive Patients With a Large Infarct Core (ANGEL-ASPECT) trial. Futile recanalization was defined as a modified Rankin Scale (mRS) score of >3 at 90 days despite successful reperfusion (extended Thrombolysis in Cerebral Infarction scale ≥2b). Participants were divided into futile (mRS >3) and no-futile (mRS ≤3) recanalization groups. Multivariable logistic regression was used to develop the predictive scale, with model performance assessed via a receiver operating characteristic (ROC) curve and Hosmer-Lemeshow test. RESULTS:Of 146 patients, 74 had futile recanalization. A six-item scale (0-6 points) was developed, including gender, age, systolic blood pressure, admission National Institutes of Health Stroke Scale score, blood glucose, and neutrophil-to-lymphocyte ratio. The scale showed good predictive performance (area under the ROC curve (AUC) 0.806, 95% CI 0.737 to 0.876) and good calibration (Hosmer-Lemeshow test, P=0.837). The optimal cut-off value of the scale was ≥3 points with 81% sensitivity, 70% specificity, and 76% accuracy. CONCLUSIONS:The pre-EVT scale could effectively predict 90-day futile recanalization before EVT, providing a valuable tool for clinical decision-making and risk stratification in patients with LVO and large core infarction.

BACKGROUND:Predicting futile recanalisation following endovascular treatment (EVT) in patients with large core infarctions is crucial for guiding clinical decisions, optimising perioperative management and improving healthcare resource allocation. This study aimed to compare four machine learning (ML) algorithms and identify the most effective model for preinterventional prediction of futile recanalisation. METHODS:Patients achieving successful reperfusion (expanded Thrombolysis in Cerebral Infarction Score≥2b) from the EVT in Acute Anterior Circulation Large Vessel Occlusive Patients With a Large Infarct Core trial were stratified into two groups: no-futile recanalisation (90-day modified Rankin Scale (mRS) 0-3) and futile recanalisation (mRS 4-6). The least absolute shrinkage and selection operator regression method was used for feature selection, and four ML algorithms, including logistic regression, support vector machine (SVM), decision tree and random forest, were applied. Model performance was evaluated using receiver operating characteristic curves, calibration plots and decision curve analysis. Feature importance was ranked using SHapley Additive exPlanation (SHAP) values. RESULTS:Among 146 patients, 74 experienced futile recanalisation. Eight predictors were identified and ranked by SHAP analysis from highest to lowest importance: sex, age, National Institutes of Health Stroke Scale, glucose, systolic blood pressure, neutrophil-to-lymphocyte ratio, fibrinogen and occlusion site. Among the four models, the SVM model achieved the highest area under the curve of 0.891 (95% CI 0.837 to 0.945), along with good calibration (Hosmer-Lemeshow test, p=0.103) and clinical utility. CONCLUSION:The SVM model emerges as the optimal predictive tool for futile recanalisation following EVT in patients with large core infarction. Nevertheless, external validation is required to confirm its performance before clinical application. TRIAL REGISTRATION NUMBER:NCT04551664.

Introduction Systemic inflammation is associated with poor outcomes in symptomatic intracranial atherosclerotic stenosis (sICAS); however, the underlying mechanisms remain unclear. We investigated whether urinary albumin-to-creatinine ratio (UACR), as a clinically accessible marker of endothelial dysfunction-related microvascular injury, may mediate the association between inflammation and prognosis.Patients and methods We analysed 2,267 patients with sICAS from the Third China National Stroke Registry. High-sensitivity C-reactive protein (hsCRP) ≥ 2 mg/L and UACR ≥ 30 mg/g were exposures, and poor outcome (modified Rankin Scale (mRS) 3–6) at 90 days was the endpoint. Multivariable logistic regression assessed independent associations, and mediation analysis quantified the contribution of UACR to the hsCRP–outcome association. In a 217-patient sICAS-Computational Fluid Dynamics (sICAS-CFD) cohort, patient-specific models examined links between UACR and post-stenotic perfusion.Results Both high-sensitivity C reactive protein (hsCRP) ≥2 mg/L (adjusted OR (aOR) 1.43, 95% CI 1.12 to 1.84) and UACR ≥30 mg/g (aOR 1.91, 95% CI 1.49 to 2.45) were independently associated with 90-day mRS 3–6. In a prespecified mediation framework, UACR accounted for an estimated 22.2% of the association between elevated hsCRP and 90-day poor outcome (p=0.008), with larger indirect effects in patients with elevated systolic blood pressure (proportion mediated (PM) 17.5%) or diabetes (PM 26.4%; p<0.05), consistent with systemic microvascular vulnerability. In the computational fluid dynamics cohort, hypoperfused patients with poststenotic mean arterial pressure ≥70 mm Hg exhibited higher UACR than those with lower pressure (p=0.040).Discussion and conclusion In sICAS, UACR statistically mediated the association between inflammation and functional outcome, and higher UACR was exploratorily associated with poststenotic perfusion measures, providing exploratory haemodynamic context that may help explain variation in perfusion vulnerability.

Abstract Background and aims Cardioembolic acute ischemic stroke (AIS) is a leading global cause of disability and mortality, with endovascular treatment (EVT) as the first-line strategy for large vessel occlusion (LVO). However, the optimal EVT approach—bridging therapy (intravenous thrombolysis [IVT] followed by EVT) versus direct EVT—remains controversial in this specific patient population. Methods We conducted a multicenter observational study of AIS patients with middle cerebral artery occlusion (MCAO), symptom onset-to-hospital arrival within 24 hours, and cardioembolic etiology (per TOAST classification), who underwent either bridging therapy or direct thrombectomy. Eligible patients were 1:1 propensity score-matched (PSM). The primary outcome was a 90-day modified Rankin Scale (mRS) score of 0–2. Secondary outcomes included 90-day mRS score of 0–1, early neurological deterioration (END), and 90-day all-cause mortality. Results A total of 691 patients were enrolled (230 bridging therapy; 461 direct thrombectomy). After PSM, 422 matched patients were analyzed. No significant between-group differences were observed in 90-day mRS 0–2 (44.23% versus 43.20%; P=0.83), 90-day mRS 0–1 (32.85% versus 36.59%; P=0.43), or END (10.48% versus 7.62%; P=0.31). However, the bridging therapy group had significantly lower 90-day all-cause mortality than the direct thrombectomy group (18.11% versus 34.04%; odds ratio, 0.43 [95% CI, 0.23-0.80]; P = 0.008). Conclusions For cardioembolic AIS patients with MCAO, bridging and direct thrombectomy yield comparable functional outcomes, while bridging therapy is associated with a reduced 90-day mortality rate. Conflict of interest All authors: nothing to disclose

BACKGROUND:The quantitative insulin-sensitivity check index (QUICKI) has an excellent linear correlation with the glucose clamp index of insulin sensitivity (SIClamp). OBJECTIVE:It is important to investigate whether QUICKI would be useful index of insulin resistance (IR) to predict clinical outcome in ischemic stroke (IS) patients without type 2 diabetes mellitus (T2DM). METHODS AND MATERIAL:Prospective cohort patients who were diagnosed with IS and without a history of T2DM in the ACROSS-China registry were included from May 2008 to December 2009. And, QUICKI was calculated by the formula: 1/[log (fasting insulin, μU/mL) + log (fasting blood glucose, mg/dL)] and split into four quartiles. RESULTS:Of 1149 study participants, recurrent IS, all-cause death, and poor outcome occurred in 169 (14.71%), 72 (6.53%), and 261 (22.72%) cases, respectively in 1-year follow-up. Multivariable Cox proportional hazards analyses showed that the risk of incident primary endpoints was associated with a lower QUICKI quartile. In the Cox proportional hazard model, patients with the first QUICKI had an association with IS recurrence (adjusted hazard ratio, 2.90; 95% CI, 1.26-6.67; P = 0.001) and poor outcome (adjusted hazard ratio, 2.53; 95% CI, 1.06-5.99; P = 0.035), compared with those in the fourth quartile. Furthermore, the Kaplan-Meier survival analysis shown non-diabetic IS patients with a lower QUICKI had a higher mortality. CONCLUSIONS:QUICKI as an insulin sensitivity index might be a potential predictor of clinical outcomes for acute IS patients without T2DM.

Background and Objectives Enlarged perivascular spaces (EPVSs), particularly in the basal ganglia (BG), are indicators of microvascular dysfunction and impaired glymphatic clearance, which may influence stroke outcomes. Determining the threshold below which endovascular therapy (EVT) confers no additional benefit is clinically important for patients with large ischaemic infarcts. Methods This post-hoc analysis utilized data from the ANGEL-ASPECT trial (NCT04551664), a multicentre, randomized controlled trial of 456 acute ischaemic stroke (AIS) patients with anterior circulation large vessel occlusion (LVO) and a large ischaemic core. Among these patients, 226 who with completed, high-quality brain magnetic resonance imaging (MRI) were included. BG-EPVS severity was assessed on T2-weighted MRI and categorized as none-to-mild, moderate, or severe. The primary outcome was the 90-day modified Rankin scale (mRS) score. Results EVT significantly improved 90-day mRS outcome in patients with none-to-mild (adjusted common odds ratio [cOR] 5.50, 95% CI: 2.72-11.16, P < 0.001) and moderate (adjusted cOR 4.03, 95% CI, 1.46-11.15, P = 0.007) BG-EPVS. However, the benefit was markedly attenuated and not statistically significant in patients with severe BG-EPVS (adjusted cOR, 1.07 95% CI, 0.25-4.67, P = 0.926). EVT also increased the likelihood of achieving favourable functional outcomes (mRS scores of 0-2 and 0-3) and early neurological improvement (ENI) in the none-to-mild BG-EPVS subgroup, and favourable outcome (mRS score of 0-2) in the moderate BG-EPVS subgroup, but not in the severe BG-EPVS subgroup. Significant treatment-by-BG-EPVS interactions were observed for achieving an mRS score of 0-3 (P_interaction = 0.005) and ENI (P_interaction = 0.029). Conclusions EVT was associated with significantly improved 90-day functional outcomes in LVO-AIS patients with a large ischaemic core and none-to-mild or moderate BG-EPVS, whereas this benefit was not observed in those with severe BG-EPVS. Given the limited power in subgroup analyses, these findings should be considered hypothesis-generating and warrant validation in larger, adequately powered randomized controlled trials.

AIMS:This study aimed to examine the cross-sectional and longitudinal associations between cardiovascular-kidney-metabolic (CKM) syndrome stages and brain macrostructure and microstructure. MATERIALS AND METHODS:We conducted a prospective, community-based cohort study using data from 3067 adults aged 50-75 years. Participants were classified using the American Heart Association CKM staging system (Stages 0-4). Brain MRI was performed across three waves to assess global/regional volumes, white matter hyperintensity volume (WMHV) and diffusion tensor imaging (DTI) metrics. Adjusted linear regression and linear mixed-effects models were used. RESULTS:Among 3038 participants (mean age 61.9 years, 53.6% female), cross-sectional analyses revealed that advanced CKM stages (3-4) were significantly associated with reduced total brain, grey matter and cerebral white matter volumes, and increased WMHV. Longitudinally, higher baseline CKM stages (particularly Stages 2-3) were associated with accelerated declines in these brain volumes and faster WMHV progression over a median 4.7-year follow-up. DTI analyses further demonstrated a stage-dependent pattern of progressive white matter microstructural deterioration. This evolution progressed from focal alterations in early stages to widespread integrity loss in Stage 4, characterised by significant reductions in fractional anisotropy and elevated mean, axial and radial diffusivities. CONCLUSIONS:Our findings indicate that CKM syndrome severity is associated with abnormalities in brain macrostructure and microstructure. This is evidenced by both progressive white matter microstructural deterioration, which is detectable early, and concomitant, albeit more modest, declines in brain macrostructure. These results underscore the importance of early identification and monitoring of CKM syndrome to help mitigate or delay subsequent decline in brain health.

Abstract Background and aims Whether pulse pressure (PP) and mean arterial pressure (MAP), reflecting arterial stiffness and perfusion status respectively, could guide antihypertensive strategy selection following acute ischemic stroke (AIS) remains unclear. We aimed to evaluate the effect of early antihypertensive treatment on clinical outcomes in AIS patients, stratified by the levels of MAP and PP. Methods A secondary analysis of the China Antihypertensive Trial in Acute Ischemic Stroke II (CATIS-2) trial was performed, which randomized 4810 AIS patients (within 24-48 hours of onset and elevated SBP) to immediate or delayed antihypertensive treatment on day 8. The primary outcome was functional dependency or death (modified Rankin Scale [mRS] score ≥3) at 90 days. Results Significant interaction between MAP and treatment assignment was detected for the primary outcome in the higher PP subgroup (P for interaction = 0.049), but not in the lower PP subgroup (P for interaction = 0.49). Compared with delayed treatment, early antihypertensive treatment significantly increased the risk of the primary outcome only in patients with higher PP combined with lower MAP (14.2% vs 8.1%; aOR 1.85, 95% CI 1.21-2.85; P=0.005). Similar trends were observed for death or major disability and the ordinal distribution of mRS scores (P for interaction = 0.02 and 0.005, respectively) at 14 days or hospital discharge. Conclusions Early antihypertensive therapy may be associated with an increased risk of functional dependency or death at 90 days among AIS patients with higher PP combined with lower MAP. Simultaneous consideration of PP and MAP may inform antihypertensive strategy selection after AIS. Conflict of interest Zilin Zhao.nothing to disclose; Yuesong Pan.nothing to disclose; Liping Liu. nothing to disclose

BACKGROUND:The effect of the difference between cystatin C- and creatinine-based estimated glomerular filtration rates (eGFRdiff) on stroke outcomes is unclear. This study investigated the association between eGFRdiff and stroke prognosis. METHODS:Participants with ischaemic stroke or transient ischaemic attack were recruited from the Third China National Stroke Registry, a multicenter, prospective cohort. eGFRdiff was calculated using the absolute difference (eGFRabdiff defined as cystatin C-based (eGFRcys) minus creatinine-based (eGFRcr)) and the ratio (eGFRrediff) between eGFRcys and eGFRcr estimates. eGFRabdiff (< -15, -15-15, ≥ 15 mL/min/1.73 m2) and eGFRrediff (< 0.6, ≥ 0.6) were analyzed. Time-updated eGFRdiff (ΔeGFRdiff) was defined as the change from baseline to 1-year blood re-examination and tertiled. Outcomes included 5-year all-cause mortality, stroke disability, and stroke recurrence. RESULTS:Among 10,293 participants, 35.2% had an eGFRabdiff < -15 mL/min/1.73 m2, and 3.5% had an eGFRrediff < 0.6. Compared with midrange eGFRabdiff, participants with eGFRabdiff < -15 mL/min/1.73 m2 had an odds ratio (OR) of 1.19 (95% confidence interval (CI), 1.05-1.35) for disability and a hazard ratio (HR) of 1.28 (95% CI, 1.12-1.46) for mortality. eGFRrediff < 0.6 was associated with a higher risk for disability (OR, 1.66; 95% CI, 1.25-2.19) and mortality (HR, 1.49; 95% CI, 1.17-1.90). Participants with the largest ΔeGFRdiff declines had higher mortality (OR, 1.44; 95% CI, 1.14-1.82) and borderline disability risk significance (HR, 1.25; 95% CI, 0.96-1.61). CONCLUSIONS:Significant and widening eGFRdiff were independently associated with increased risks of post-stroke disability and mortality, highlighting the importance of monitoring eGFRcys and eGFRcr in stroke management.

Watershed infarction (WI) is heterogeneous. This study aims to explore the effect of clopidogrel-aspirin in patients with WI and which WI patterns could gain more benefits. Patients are classified into cortical WI (CWI) (n = 484), internal WI (IWI) (n = 372), CWI+IWI (n = 410), and non-WI (n = 4,033) according to diffusion-weighted magnetic resonance imaging. The results show that patients with WI treated with clopidogrel-aspirin have a lower risk of stroke recurrence compared to aspirin at 90 days (hazard ratio [HR], 0.67; 95% confidence interval [CI], 0.49-0.93). Specifically, patients receiving clopidogrel-aspirin show a lower rate of recurrent stroke than those receiving aspirin in IWI (HR, 0.54; 95% CI, 0.30-0.97), and with a similar trend in CWI+IWI, but not significant in CWI (p for interaction = 0.41). Clopidogrel-aspirin does not increase moderate-to-severe bleeding across WI patterns. This study reveals that the effect of clopidogrel-aspirin appears consistent across WI subgroups, but it might be more effective in patients with IWI. This study is registered at Clinicaltrials.gov (NCT03635749).

ABSTRACT:In recent decades, the advent of revascularization treatments (RVTs), such as intravenous thrombolysis (IVT) and endovascular therapy, has significantly improved clinical outcomes in patients with acute ischemic stroke (AIS). However, stroke-associated pneumonia (SAP) remains a common complication that has a negative impact on the prognosis. This review addresses the mechanisms underlying the development of SAP in patients with AIS, evaluates risk factors, and discusses therapeutic and preventive measures in the era of RVTs. Despite advances in acute stroke care, the incidence of SAP remains high, particularly in patients who receive endovascular treatment (EVT), possibly because of prolonged mechanical ventilation, the effects of anesthesia, and stays in the intensive care unit. Immunodepression, dysphagia, lung damage, and changes in the gut microbiota are central to the pathogenesis of SAP. Current prevention strategies, including screening for dysphagia, oral hygiene, and immunomodulation, show promise but require further validation. Future research should focus on integrating biomarkers and imaging markers for early prediction of SAP and developing targeted interventions to improve patient outcomes.

Asymptomatic carotid artery stenosis (aCAS) increases the risk of ischemic stroke despite lacking clinical symptoms. This study sought to characterize the serum metabolic profile of aCAS and to identify potential biomarkers associated with plaque vulnerability by integrating metabolomics with radiomics. Untargeted metabolomic profiling was performed using liquid chromatography-tandem mass spectrometry (LC-MS/MS) on 72 participants, including 36 aCAS patients and 36 age- and sex-matched healthy controls (HC). Multivariate and univariate statistical analyses were conducted to screen differential metabolites. Candidate biomarkers were prioritized based on variable importance in projection (VIP) scores and random forest (RF) modeling. Plaque vulnerability features were quantified by high-resolution magnetic resonance vessel wall imaging (HR-VWI), and multi-omics analysis assessed associations between metabolites and plaque characteristics. A total of 144 significantly altered metabolites were identified between the aCAS and HC groups. Pathway enrichment analysis indicated that these differential metabolites were predominantly involved in lipid, purine, amino acid, nucleotide, and energy metabolism. Notably, 12R-HETrE, 9S-HOTrE, oleoylcarnitine, crichetocholic acid and 1β,3α,7α-trihydroxy-5β-cholan-24-oic acid-were significantly associated with radiomic markers of plaque vulnerability. This study delineates metabolic alterations in aCAS patients and identifies potential serum metabolic biomarkers associated with plaque vulnerability. Further validation is required.

IntroductionCerebral small vessel disease (CSVD) and motoric cognitive risk syndrome (MCR) are both associated with adverse outcomes in older adults. Factors associated with MCR in CSVD remain poorly understood. We aimed to explore factors associated with MCR and its components (slow gait and subjective cognitive complaints [SCCs]) in CSVD, and to evaluate exploratory association-based multivariable models.MethodsThis cross-sectional study included CSVD patients aged ≥55 years without possible dementia based on education-adjusted MoCA screening from the cognitive subgroup of a national registry. Demographics, clinical variables, physical activity, and CSVD neuroimaging markers were assessed. MCR was defined as co-existing slow gait (age- and sex-adjusted) and SCCs (single-item memory complaint from the 15-item Geriatric Depression Scale). Logistic regression and receiver operating characteristic analyses were performed to identify associated factors and evaluate models. Firth penalized logistic regression and bootstrap internal validation were additionally performed to assess sparse-data bias and optimism in model discrimination.ResultsAmong 225 patients (mean age 65.4 years, 54.2% male), MCR prevalence was 16.4%. In multivariable models, MCR was associated with lower average systolic blood pressure and high total CSVD burden, while physical inactivity showed a positive but imprecise association because of sparse exposure. SCCs were associated with greater juxtacortical white matter hyperintensity volume and higher total CSVD burden. Slow gait was associated with dyslipidemia, poorer functional status, and higher basal ganglia perivascular spaces. The comprehensive exploratory model integrating demographic, clinical, and neuroimaging factors achieved areas under the curve of 0.732 for MCR, 0.733 for SCCs, and 0.770 for slow gait; the corresponding optimism-corrected AUCs were 0.691, 0.696, and 0.725, respectively.ConclusionIn this exploratory cross-sectional analysis, MCR in CSVD patients showed associations with vascular, lifestyle-related, and neuroimaging markers. However, given the small number of MCR events, the single-item SCC assessment, the lack of temporality, and the limited persistence of associations after FDR correction, these findings should be interpreted as hypothesis-generating.

Background: The hyperdense middle cerebral artery sign (HMCAS) observed on noncontrast computed tomography is associated with thrombus composition and thrombectomy outcomes. The impact of HMCAS on the efficacy of endovascular therapy (EVT) in patients with large core infarcts remains unclear. Methods: This analysis uses data from the ANGEL-ASPECT (Endovascular Therapy in Acute Anterior Circulation Large Vessel Occlusive Patients With a Large Infarct Core) trial, a multicenter randomized controlled trial conducted in China. Patients with acute ischemic stroke and anterior-circulation large-vessel occlusion were categorized according to whether HMCAS was present on baseline noncontrast computed tomography. The primary outcome was the 90-day modified Rankin Scale score. Results: Of the 432 patients included in this analysis, 33% were HMCAS positive on baseline noncontrast computed tomography. In the EVT-treated patients, patients with HMCAS had worse functional outcomes than those without HMCAS (adjusted relative risk, 0.44 [95% CI, 0.26-0.73]; P=0.002). Patients with HMCAS required a greater number of thrombectomy passes (P<0.001). Among patients without HMCAS, EVT was associated with better functional outcomes than medical management (generalized odds ratio [OR], 2.78 [95% CI, 1.80-4.27]; P<0.001), whereas this benefit was not statistically significant among patients with HMCAS (adjusted OR, 1.69 [95% CI, 0.93-3.08]; P=0.09). There was no significant interaction between HMCAS status and treatment assignment (P=0.19). Conclusions: In this subgroup analysis comparing EVT with medical management, we found no statistically significant treatment-by-HMCAS status interaction, indicating that the benefits of EVT extend to patients with large core infarcts irrespective of HMCAS status. However, the magnitude of benefit appears greater in patients without HMCAS, whereas those with HMCAS tend to have a poorer overall prognosis. Registration: URL: https://www.clinicaltrials.gov; Unique Identifier: NCT04551664.

Background and purpose Recent randomised clinical trials have shown that endovascular treatment (EVT) for patients with acute ischaemic stroke (AIS) and a large infarct core is safe and effective. This study sought to identify which factors predict favourable outcomes in AIS patients with a large infarct core who received EVT in the ANGEL-ASPECT trial.Methods Patients from the ANGEL-ASPECT trial receiving EVT were enrolled in this analysis. They were categorised based on 90-day outcomes: good functional outcome (modified Rankin Scale (mRS) score 0–2) and independent ambulation (mRS score 0–3). A comparison of baseline and procedural characteristics was performed across the groups and logistic regression was performed to identify predictors of favourable outcomes.Results Of 230 AIS participants with large infarct core undergoing EVT, independent predictors differed between outcome levels. For functional independence (mRS 0–2), predictors were male sex, lower systolic blood pressure (SBP) and National Institutes of Health Stroke Scale (NIHSS) score, smaller infarct volume, fewer thrombectomy attempts, and notably, the presence of early neurological improvement (ENI) at 36 hours (OR 19.62, 95% CI 2.28 to 168.52). For independent ambulation (mRS 0–3), predictors were younger age, lower SBP and NIHSS score, successful reperfusion, lower platelet-to-lymphocyte ratio and absence of decompressive hemicraniectomy (OR 20.00, 95% CI 2.04 to 196.08).Conclusions This analysis delineates distinct predictors for different levels of recovery after EVT in large-core stroke. Beyond confirming the prognostic value of established factors (such as age, NIHSS and reperfusion), it highlights the novel high-impact prognostic factors for large-core AIS patients post-EVT: ENI for functional independence. Furthermore, the need for decompressive hemicraniectomy, a marker of severe cerebral oedema, was strongly linked to a lower probability of achieving independent ambulation. These findings may aid in early prognostication and refined patient management for this high-risk population.Trial registration number NCT04551664.

Background: The 12-month findings from the Balloon Angioplasty for Symptomatic Intracranial Artery Stenosis (BASIS) trial demonstrated that balloon angioplasty combined with aggressive medical management (AMM) improved clinical outcomes compared with AMM alone in patients with symptomatic intracranial atherosclerotic stenosis (sICAS). However, the long-term durability of the efficacy and safety of balloon angioplasty for sICAS remains unclear. Methods: This study represented a prespecified long-term follow-up analysis of a multicenter, randomized, open-label, blinded end point clinical trial conducted at 31 clinical centers across China. Eligible participants were patients aged 35 to 80 years with 70% to 99% stenosis of a major intracranial artery and recent symptomatic events, who were randomly assigned in a 1:1 ratio to receive balloon angioplasty plus AMM or AMM alone. The prespecified main long-term clinical outcome was any ischemic or hemorrhagic stroke in the territory of the qualifying artery or all-cause death through 36 months after enrollment. Prespecified secondary long-term outcomes included any ischemic or hemorrhagic stroke in the territory of the qualifying artery or all-cause death through 24 months after enrollment, mRS scores at 24 and 36 months, intracranial hemorrhage and the composite of stroke, myocardial infarction, or vascular death through 24 and 36 months. Findings: Among 501 initially eligible patients, 475 patients (94.8%) completed the 3-year follow-up, including 234 patients in the balloon angioplasty group and 241 patients in the AMM group, with well-balanced baseline characteristics between the two groups. The incidence of main long-term clinical outcome was significantly lower in the balloon angioplasty group than in the AMM group at 3years (4.4% vs. 12.3%; HR, 0.33; 95% CI, 0.17–0.67; P=0.002), with ischemic stroke within the territory of the qualifying artery within 3years as the predominant event (2.0% vs. 10.7%). The landmark analysis indicates that among patients who were event-free at 1 year (n=241 in the balloon angioplasty group; n=229 in the AMM group), the incidence of the main long-term clinical outcome between 1 and 3 years was 1.2% versus 3.2% (HR, 0.34; 95% CI, 0.09–1.28; P=0.109). The incidence of any stroke in the territory of the qualifying artery or all-cause death within 2 years after enrollment was also lower in the balloon angioplasty group than in the AMM group (4.0% vs. 11.9%; HR, 0.32; 95% CI, 0.15–0.65; P=0.002). Similarly, The functional outcomes significantly favored the balloon angioplasty group both at 2 years (mRS, generalized OR, 1.21; 95% CI, 1.02-1.40; P=0.04) and 3 years (mRS, generalized OR, 1.38; 95% CI, 1.16-1.60; P=0.002). Interpretation: In this prespecified 3-year follow-up of the BASIS randomized clinical trial, the reduction in stroke-related clinical events achieved within the first year after angioplasty was sustained through 3 years, with few additional events occurring beyond 1year. These findings support the durability of the early treatment effect rather than the emergence of new long-term benefit, validating the regimen for secondary stroke prevention among high-risk patients.

BACKGROUND:The antithrombotic strategies for symptomatic intracranial atherosclerotic stenosis (sICAS) remains challenging. Dual pathway inhibition (DPI) has demonstrated clinical benefit in coronary and peripheral artery disease. AIMS:This study aimed to evaluate the efficacy of DPI with low-dose rivaroxaban plus antiplatelet therapy (APT) compared with APT alone on recurrent stroke with sICAS. METHODS:This prospective cohort study included patients with sICAS identified from the Ischemic Cerebrovascular Disease Database of the First Affiliated Hospital of Zhengzhou University between January 2019 to August 2023. Low-dose rivaroxaban was prescribed off-label to patients in the DPI group. The outcomes were ischemic stroke, transient ischemic attack (TIA), acute coronary syndrome (ACS), all-cause death and cardio-cerebrovascular death within 1 year of discharge. Cox regression with inverse probability of treatment weighting (IPTW) was applied to compare outcomes between the DPI and APT groups. The win-ratio method was used to assess the major adverse cardiovascular events (MACE), prioritized in the order of all-cause death, recurrent ischemic stroke or TIA, and ACS. RESULTS:Among the 1217 patients with sICAS, 131 (10.8%) received DPI therapy. The recurrence rate of ischemic stroke was lower in the DPI group compared to the APT group (8/131 [6.1%] vs 136/1086 [12.5%]). DPI significantly reduced the risk of ischemic stroke recurrence (HR = 0.46, 95% CI: 0.23-0.94, p = 0.034) and the incidence of MACE (HR = 0.53, 95% CI: 0.29-0.97, p = 0.041) during the 1-year follow-up, consistent with the IPTW-based cohort (HR = 0.35, 95% CI: 0.16-0.76, p = 0.008; HR = 0.43, 95% CI: 0.22-0.83, p = 0.012). The win-ratio analysis of MACE favored DPI therapy (win ratio = 2.34, 95% CI: 1.41-3.90, p = 0.001). Symptomatic intracranial hemorrhage, fatal bleeding, and hospitalization for gastrointestinal bleeding were infrequent in this cohort. CONCLUSIONS:DPI therapy may be associated with a lower risk of recurrent stroke compared with antiplatelet therapy alone in patients with sICAS. These findings warrant further investigation through large-scale randomized controlled trials.

BACKGROUND AND PURPOSE:Endovascular treatment (EVT) is superior to medical management (MM) for patients with acute large infarcts. However, evidence remains limited for patients with large infarcts with extracranial internal carotid artery occlusion (e-ICAO) . This study compares EVT and MM in patients with large infarcts due to e-ICAO. METHODS:Patients with e-ICAO were selected from the ANGEL-ASPECT randomized controlled trial conducted at 46 stroke centers across China between October 2, 2020 and May 18, 2022. The efficacy and safety of EVT and MM were compared in these patients. The primary outcome was the 90-day modified Rankin Scale (mRS) score, and secondary outcomes were 90-day/1-year functional independence and independent ambulation and 1-year mRS score. Safety endpoints were symptomatic intracranial hemorrhage (sICH) and 90-day mortality. RESULTS:Of 456 enrolled patients, 76 (16.7%) had e-ICAO (41 EVT, 35 MM). 90-day mRS distribution (4 (2-6) vs 4 (3-5), adjusted common OR (acOR) 1.27 (95% CI 0.54 to 2.98); P=0.579), 90-day independent ambulation (46.3% vs 31.4%, aRR 1.29 (95% CI 0.70 to 2.38); P=0.415), 90-day functional independence (29.3% vs 5.7%, aRR 3.74 (95% CI 0.89 to 15.61); P=0.071), 1-year mRS score (4 (2-6) vs 4 (3-5), acOR 0.86 (95% CI 0.35 to 2.10), P=0.735), 1-year independent ambulation (48.7% vs 46.9%, aRR 0.79 (95% CI 0.48 to 1.31); P=0.367), and 1-year functional independence (30.8% vs 15.6%, aRR 1.76 (95% CI 0.67 to 4.65); P=0.252) were not significantly different between the EVT and MM groups. sICH was higher in the EVT group than in the MM group (2.4% vs 0, P=0.356) and 90-day mortality (19.5% vs.8.6%, aHR 2.17 (95%CI 0.59 to 8.03); P=0.247) was similar between the two groups. CONCLUSIONS:In patients with large infarcts and e-ICAO, EVT did not improve clinical outcomes at either 90 days or 1 year compared with MM without increasing the risk of sICH and mortality. TRIAL REGISTRATION NUMBER:NCT04551664.

BACKGROUND:Sex differences may influence outcomes of dual antiplatelet therapy after acute ischemic stroke or transient ischemic attack (TIA). We evaluated whether treatment effects of clopidogrel plus aspirin differ by sex in patients with mild ischemic stroke or high-risk TIA. . RESEARCH DESIGN AND METHODS:This prespecified subgroup analysis used data from the INSPIRES trial, a multicenter, double-blind, placebo-controlled randomized trial conducted in China. Patients aged 35-80 years enrolled within 72 hours of symptom onset were randomized to clopidogrel plus aspirin or aspirin alone. The primary efficacy outcome was new stroke within 90 days, and the primary safety outcome was moderate-to-severe bleeding. Sex-by-treatment interaction was assessed. RESULTS:Among 6,100 patients (female 35.8%), new stroke occurred in 7.9% of females and 6.95% of males in the clopidogrel plus aspirin group, compared with 9.9% and 8.71% in the aspirin group, respectively. No significant sex-by-treatment interaction was observed for stroke prevention. Rates of moderate-to-severe bleeding were low and similar between females and males, with no evidence of interaction. CONCLUSIONS:In this prespecified subgroup analysis, clopidogrel plus aspirin showed no sex-based differences in efficacy or safety. These findings do not support sex-specific treatment effects. . TRIAL REGISTRATION:ClinicalTrials.gov (NCT03635749).