Introduction and Objective: T2D management focuses on improving glycemic control and reducing cardiovascular (CV) risk. Dapagliflozin (Dapa) has shown CV and renal benefits. HTD1801, an anti-inflammatory metabolic modulator (AIMM) that activates AMPK and inhibits the NLRP3 inflammasome, also improves cardiometabolic and renal parameters. The HARMONY study evaluated the efficacy and safety of HTD1801 vs Dapa in patients with T2D. Methods: Key entry criteria of this Phase 3 double-blind, active-controlled study: T2D, HbA1c 7.0%-10.5%, FPG ≤250.5 mg/dL, and stable metformin use ≥8 weeks. After a 4-week run-in, patients were randomized 1:1 to HTD1801 1000 mg BID (N=186) or Dapa 10 mg QD (N=181). Metformin remained stable. The primary endpoint was HbA1c change from baseline at Week 24 (non-inferiority margin of 0.4%). Results: At Week 24, HTD1801 produced an HbA1c reduction of -1.12% vs -0.93% for Dapa with a LS mean difference of -0.20% (95% CI, -0.37%, -0.03%; p<0.001), confirming non-inferiority. More patients treated with HTD1801 vs Dapa achieved HbA1c <7%. HTD1801 showed superiority for key lipid parameters and eGFR increased in the overall population with HTD1801 compared to no change with Dapa. Treatment-emergent adverse events occurred in 73.1% (HTD1801) vs 64.1% (Dapa) of patients. Conclusion: HTD1801 provided glycemic control comparable to Dapa, with more pronounced and distinctive effects on CV risk factors and therefore may provide a unique treatment option for patients with T2D. Disclosure L. Ji: None. Z. Cheng: None. H. Cai: None. J. Han: None. L. Lu: None. Q. Li: None. H. Wang: None. Y. Wang: None. J. Ma: None. C. Xu: None. D. Zhou: None. B. Lu: None. Y. Bi: None. Y. Bao: None. Z. Zhou: None. K. Liu: Employee; Current; HighTide Therapeutics Inc. L. MacConell: Employee; Current; HighTide Therapeutics Inc. M. Yu: Employee; Current; HighTide Therapeutics Inc. L. Liu: Employee; Current; HighTide Therapeutics Inc.

Background Stroke remains a leading cause of mortality and adult disability in China, imposing a substantial disease and socioeconomic burden on society, yet nationally representative epidemiological and real-world inpatient care data remain insufficient. Methods This study integrated data from the Global Burden of Disease 2023, the Hospital Quality Monitoring System (7536 hospitals) in 2023, and the 2021 National Mortality Surveillance System to systematically assess the epidemiology, disease burden, inpatient care patterns, clinical outcomes and average costs of stroke per hospitalisation in China. Results In 2023, China reported 4.23 million incident cases, 26.68 million prevalent cases and 2.05 million deaths from stroke. Despite declining age-standardised incidence and mortality, ischaemic stroke (IS) prevalence continued to increase, while haemorrhagic stroke remains the principal contributor to disability-adjusted life years. Real-world inpatient data showed that males and older adults accounted for higher proportions of stroke admissions. Stroke admissions were predominantly concentrated in tertiary public hospitals with marked regional variation. Haemorrhagic stroke has substantially higher in-hospital mortality (intracerebral haemorrhage, ICH: 4.23%; subarachnoid haemorrhage, SAH: 4.08% vs IS: 0.49%) and adverse discharge outcomes than IS. Tertiary hospitals exhibited higher mortality (1.19% vs 0.62%) but lower 0–31-day readmission rates (1.19% vs 1.63%) than secondary hospitals, whereas private hospitals showed longer hospital stays (10.54 vs 9.86 days) and higher readmission rates (1.88% vs 1.34%) than public institutions. The mean hospitalisation cost was RMB13 927 (US$1900) per admission, with substantially higher costs for SAH and ICH than for IS. Conclusions This nationwide analysis provides comprehensive real-world evidence on the epidemiological burden, inpatient care patterns, clinical outcomes and hospitalisation costs of stroke in China, identifying substantial national, regional and hospital-level variations that may inform future research and quality improvement efforts.

Chronological age is a strong predictor of poor outcomes after ischemic stroke but may not fully capture underlying biological vulnerability. This study investigated whether age-related brain atrophy and plasma YKL-40, a marker of astroglial inflammation, mediate the association between age and the one-year risk of ischemic stroke recurrence or all-cause mortality. Data were obtained from 4,305 participants enrolled in the Third China National Stroke Registry. Baseline brain atrophy was quantified from structural T1-weighted MRI using an automated deep learning–based pipeline (FastSurfer), yielding hemispheric cortical and white matter volumes that were modeled as indicators of a latent atrophy construct. Structural equation modeling was applied to estimate direct and indirect pathways linking age, brain atrophy, YKL-40, and one-year composite outcomes, adjusting for sex, atrial fibrillation or flutter, hypertension, and diabetes, with indirect effects evaluated using 5,000 bootstrap resamples. The total effect of age on one-year outcomes was not significant (β = −0.011; 95

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

Stroke remains a leading cause of death and disability worldwide. In response, many governments have developed stroke policies emphasizing prevention, early detection, timely treatment, and rehabilitation. However, the implementation of those strategies remains uneven, challenged by fragmented health systems, unequal access to care, and resource constraints. Digital health tools provide robust solutions to enhance national and regional stroke policies by improving data collection, care access and coordination, monitoring, education, and public engagement. This review explores how digital health can strengthen stroke care systems across different contexts, highlighting real-world applications, policy integration, and strategic enablers for equitable implementation.

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.

BACKGROUND:Distal embolisation (DE) is a common complication following endovascular treatment (EVT) for acute ischaemic stroke. Thrombus magnetic susceptibility may offer predictive insights into DE risk. In this study, we employed quantitative susceptibility mapping (QSM) to measure thrombus susceptibility in patients undergoing EVT and examined its association with DE occurrence. METHODS:Patients with confirmed intracranial large vessel occlusion were consecutively enrolled from a participating centre in the RESCUE-RE study (a registration study for Critical Care of Acute Ischaemic Stroke After Recanalisation). Thrombus magnetic susceptibility was quantitatively measured using three-dimensional multiecho QSM imaging. DE was defined as the appearance of new downstream occlusions on postinterventional digital subtraction angiography. The association between thrombus susceptibility metrics and the occurrence of DE was analysed using multivariable logistic regression, adjusting for relevant clinical and procedural variables. RESULTS:Among the 61 patients included, DE occurred in 29.5% of patients. Thrombi from patients with DE showed significantly higher mean susceptibility values (0.28±0.11 parts per million (ppm) vs 0.22±0.08 ppm, p=0.029). Multivariable analysis identified increased thrombus susceptibility as an independent predictor of DE, with an OR of 2.38 per 0.1 ppm (95% CI 1.04 to 5.45, p=0.039), after adjusting for potential confounders such as National Institutes of Health Stroke Scale score, stroke aetiology, occlusion site, intravenous thrombolysis and time from onset to groin puncture. CONCLUSION:This study identifies thrombus magnetic susceptibility, as quantified by QSM, as a novel imaging biomarker predictive of DE during EVT. These findings highlight the potential of QSM to guide treatment decisions and stratify DE risk preoperatively, although validation in larger cohorts is warranted.

Background and purpose:Stroke is a leading cause of death globally, placing a particularly high burden on Hungary and China. Our study aimed to compare the epidemiology, acute management, and stroke prevention strategies based on Hungarian and Chinese data. Methods:We conducted a comprehensive literature review using Hungarian and Chinese epidemiological data, national health reports and guidelines, local protocols for stroke management, and publications related to prevention strategies. Data collection involved PubMed and MEDLINE databases; we also included results from the Global Burden of Disease Study to compare stroke incidence and mortality data in the two populations. The analysis of data from the two countries allowed for the identification of key trends. Results:Despite the global decline in stroke-related mortality, Hungary's age-standardized stroke mortality rate remains above the European average, while a 32% increase has been seen in stroke-related deaths since 1990 in China. Even with the implementation of national stroke prevention initiatives, an increasing trend is observed in the prevalence of cardiovascular risk factors in both countries. The stroke management protocols of both nations align with international guidelines, including recommendations for intravenous thrombolysis and mechanical thrombectomy, as well as efforts to establish stroke center networks and systems that enhance prehospital care efficiency. Conclusion:While advancements in stroke management are evident in both Hungary and China, challenges persist in optimizing stroke prevention, reducing "stroke-to-needle time", and expanding rehabilitation services.

BACKGROUND: Functional syncope and vasovagal syncope (VVS) in children both present with transient loss of consciousness (TLOC) and are clinically challenging to differentiate. This study aims to delineate the distinguishing features among factors associated with TLOC induction in these two conditions. METHODS: A total of 31 children presenting with syncope and diagnosed as functional syncope were enrolled in the functional syncope group; concurrently, 40 children presenting with syncope and diagnosed with VVS were enrolled in the VVS group. Clinical manifestations— including demographic characteristics, precipitating factors, prodromal symptoms, syncope episode characteristics, family history, and psychosocial stressors—were systematically compared between the two groups. RESULTS: Body weight was significantly higher in the functional syncope group than in the VVS group (P < 0.05). No statistically significant differences were observed between the groups in terms of sex distribution, age, body height, or baseline resting heart rate (P > 0.05). Compared with the VVS group, the functional syncope group exhibited significantly fewer identifiable triggers, fewer presyncope symptoms, and a lower prevalence of familial syncope history (all P < 0.05). Conversely, the functional syncope group demonstrated significantly longer syncope duration, higher syncope frequency, and greater exposure to emotional stress events (all P < 0.05). Disease duration did not differ significantly between the two groups (P > 0.05). CONCLUSIONS: Children with functional syncope exhibit distinct clinical profiles relative to those with VVS, characterized by fewer precipitating factors and prodromal symptoms, longer duration and higher frequency of syncope episodes, reduced familial syncope history, and increased association with emotional stress events.

Contrast-induced encephalopathy (CIE) is a recognized complication associated with the use of iodinated contrast media in angiography and vascular interventions. Typically, CIE presents on computed tomography (CT) with localized cortical enhancement, increased density in the subarachnoid space, and cerebral edema. Lesions are usually located in the deep perforating branch areas and are relatively rare. We present the case of a 61-year-old male who underwent interventional treatment for an arteriovenous fistula and was subsequently diagnosed with CIE. Twenty minutes post-procedure, the patient exhibited drowsiness, and a brain CT scan revealed symmetrical high-density lesions in the bilateral thalami. Following two days of conservative management, the patient experienced spontaneous resolution of the CT lesions without any neurological deficits. This case underscores the importance of immediate postoperative cranial imaging to exclude potential complications from angiography. Additionally, it is extremely rare for CIE to present with bilateral thalamic lesions.

Intracranial atherosclerotic stenosis (ICAS) is an important cause of ischemic stroke and transient ischemic attack (TIA), which is also associated with increased risks of cognitive impairment and dementia. The prevalence of both asymptomatic and symptomatic ICAS (asICAS and sICAS) is significantly higher in Asian populations than in Western populations. In recent years, substantial new evidence has emerged regarding the epidemiology, diagnosis, assessment, prognosis, and treatment of asICAS and sICAS. The China ICAS Research Group has developed this guideline based on published research and relevant domestic and international guidelines or expert consensus, to further clarify the definition, epidemiology, and prognosis of ICAS and the profiles of high-risk ICAS patients and provide evidence-based recommendations on screening, diagnosis, assessment, and treatment strategies of asICAS and sICAS. For imaging exams, noninvasive and contrast-independent modalities are generally suitable for screening and assessment of ICAS in stroke-free individuals with multiple risk factors as well as for routine exams of stroke patients, while contrast-dependent or invasive imaging methods may be employed for further assessment or guiding treatment decision-making in sICAS patients. In addition, vessel wall imaging is valuable for distinguishing the etiology of intracranial stenosis, particularly in young stroke patients. Multiple imaging modalities or methods are available for the assessment of cerebral perfusion, hemodynamics, and collateral circulation that may meet different needs. Regarding interventions, lifestyle modifications (healthy diet, safe exercise, smoking cessation) are recommended for both asICAS and sICAS patients. For stroke-free individuals with asICAS, controlling vascular risk factor is the primary strategy, while routine aspirin or endovascular treatment for primary stroke prevention is not recommended. For sICAS patients, the cornerstone is intensive medical management, including short-term dual antiplatelet therapy in high-risk patients (such as those with severe luminal stenosis, minor stroke, or high-risk TIA) followed by lifelong monotherapy, aggressive lipid control (targeting low-density lipoprotein cholesterol < 1.8 mmol/L), blood pressure control (<140/90 mmHg), and glycemic control (targeting HbA1c < 7.0%), with structured follow-up to enhance treatment adherence. Endovascular treatment is not recommended for sICAS with mild to moderate luminal stenosis (<70%) but may be considered for carefully selected patients with severe (70-99%), medically refractory sICAS, particularly those with hypoperfusion, with a preference to delay the intervention for more than 21 days after stroke to enhance safety.

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

For patients with acute ischemic stroke (AIS) caused by large vessel occlusion, endovascular thrombectomy (EVT) serves as the standard treatment. However, a significant proportion of patients fail to achieve functional independence despite successful recanalization. While insulin resistance (IR) has been implicated in adverse stroke outcomes, its precise impact on AIS patients undergoing EVT remains incompletely characterized. This multicenter cohort study acquired data from the RESCUE-RE registry to explore the association between IR, quantified via the triglyceride glucose (TyG) index, and 90-day functional outcomes in AIS patients undergoing EVT. The primary outcome was functional dependence, defined as a modified Rankin Scale score ≥3 at 90 days. Secondary outcomes included symptomatic intracranial hemorrhage, all-cause mortality, early neurological deterioration, and infarct volume at 24 hours, as assessed by follow-up imaging. Among 1305 patients, higher TyG index quartiles were notably associated with unfavorable clinical outcomes. Patients with the highest TyG quartile (Q4) exhibited increased odds of functional dependence (adjusted odds ratio (aOR) 1.79, 95% confidence interval (95% CI) 1.26 to 2.54), early neurological deterioration (aOR 2.48, 95% CI 1.46 to 4.22), and mortality (OR 2.62, 95% CI 1.68 to 4.09) compared with those with the lowest TyG quartile (Q1). Stratified analyses revealed that these associations were more pronounced in younger patients, females, and individuals with hypertension, diabetes, and favorable collateral circulation. Mediation analyses identified inflammation as a partial explanatory factor in the observed relationships. Insulin resistance is independently associated with deteriorated functional outcomes in AIS patients undergoing EVT.

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.

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.

Introduction Despite advances in clinical care and treatment options, recurrent stroke risk remains significant. The unmet needs and challenges in secondary stroke prevention (SSP) after a non-cardioembolic ischaemic stroke are not fully understood, leaving many patients at risk of stroke recurrence. This study summarises expert consensus on the challenges in current SSP treatment and management. Patients and methods We conducted a 2-round modified Delphi study with 13 international stroke experts. This multidisciplinary panel included stroke neurologists, a stroke nurse, a dementia care nurse with lived experience and patient advocacy group representatives. The Delphi co-chairs developed 11 statements which were presented to the experts. Agreement was sought through a 2-round, anonymous survey and a final consensus discussion. Results All 11 statements achieved consensus after the 2 survey rounds. The statements addressed key areas including the burden of recurrent stroke, treatment and lifestyle interventions, management of stroke care and future needs to enhance SSP. Conclusion This is the first Delphi-based global consensus focused specifically on unmet needs in SSP. The experts agreed on several challenges-notably, recurrent stroke risks-and consistently emphasised that the impact of recurrent stroke is underappreciated. This Delphi panel's strong consensus underscores the real-world barriers, clinical inefficiencies and unmet needs that remain in SSP treatment and management. Addressing these challenges will require sustained investment in SSP treatments, education and innovation.

BACKGROUND:The cumulative defined daily dose (cDDD) enables quantification of statin exposure, balancing therapeutic intensity and patient adherence. However, the relationship between statin cDDD and recurrence risk in ischemic stroke (IS) patients remains unclear. OBJECTIVE:The aim of this study was to investigate the impact of statin cDDD on recurrence risk in IS patients. METHODS:This prospective cohort study enrolled 728 patients with acute ischemic stroke (AIS). After 1 year of follow-up, participants were stratified into four groups (Q1-Q4) according to the quartiles of statin cDDD, and Kaplan-Meier curves were used to estimate the risk of stroke recurrence. The association between cDDD and recurrence risk was examined using restricted cubic spline (RCS) and Cox proportional hazards models, with sensitivity analyses employed to assess population heterogeneity and confirm the robustness of the findings. RESULTS:Kaplan-Meier survival analysis revealed statistically significant differences in recurrence rates across quartiles (P < 0.001). RCS analysis confirmed a nonlinear negative correlation between cDDD and recurrence risk (P for nonlinearity < 0.001). Multivariate Cox regression demonstrated that the recurrence risk in Q4 was 87.7% lower than in Q1. Sensitivity analysis further confirmed that the association between cDDD and IS recurrence risk was independent of antihypertensive or antidiabetic medication use. CONCLUSIONS:Statin cDDD shows a significant nonlinear inverse correlation with stroke recurrence, and exhibits a dose-dependent threshold effect.

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 AND OBJECTIVES:Previous studies have shown a beneficial effect of clopidogrel-aspirin and intensive statin therapy in acute ischemic stroke; however, the synergistic effect of the 2 treatments is still unclear. The aim of this study was to investigate the effect of combining clopidogrel-aspirin and immediate intensive statin in patients with acute mild ischemic stroke or transient ischemic attack (TIA). METHODS:We performed a multicenter, randomized, double-blind, placebo-controlled trial with a 2-by-2 factorial design across 222 hospitals in China. Eligible participants were patients with acute mild ischemic stroke or TIA of a presumed atherosclerotic cause within 72 hours of symptom onset. Patients were randomly assigned to receive clopidogrel plus aspirin or aspirin alone and an immediate or delayed intensive statin. The primary efficacy outcome was a new stroke (ischemic or hemorrhagic) within 90 days, and the primary safety outcome was moderate-to-severe bleeding. RESULTS:Between September 17, 2018, and October 15, 2022, 6,100 patients were enrolled (median age, 65 years; 64.2% male), of whom 1,525 each were assigned to the 4 groups. New stroke within 90 days occurred in 116 patients (7.6%) in the clopidogrel-aspirin plus immediate intensive statin group (hazard ratio [HR] 0.76, 95% CI 0.60-0.97), in 106 patients (7.0%) in the clopidogrel-aspirin plus delayed statin group (HR 0.69, 95% Cl 0.54-0.89), and in 129 patients (8.5%) in the aspirin plus immediate statin group (HR 0.85, 95% Cl 0.67 to 1.07), compared with 150 patients (9.9%) in the aspirin plus delayed intensive statin group. Moderate-to-severe bleeding occurred in 17 (1.1%) in the clopidogrel-aspirin plus immediate statin group (p = 0.047), 10 (0.7%) in the clopidogrel-aspirin plus delayed statin group (p = 0.46), and 6 (0.4%) in the aspirin plus immediate statin group (p = 0.80), compared with 7 (0.5%) in the aspirin plus delayed statin group. DISCUSSION:Among patients with mild ischemic stroke or TIA of presumed atherosclerotic cause, the combination of clopidogrel-aspirin and delayed intensive statin was superior to aspirin plus delayed intensive statin in reducing the risk of new stroke, an effect that was mainly driven by clopidogrel-aspirin and not significantly different from that of clopidogrel-aspirin plus immediate statin. The combination treatment had a low but increased risk of moderate-to-severe bleeding. TRIAL REGISTRATION INFORMATION:ClinicalTrials.gov identifier: NCT03635749. CLASSIFICATION OF EVIDENCE:This study provides Class I evidence that in patients with mild ischemic stroke or TIA of presumed atherosclerotic cause, the combination of clopidogrel-aspirin plus delayed intensive statin was superior to aspirin plus delayed intensive statin in reducing the 90-day risk of new stroke.