Background and Purpose:While stroke management has evolved rapidly, comprehensive nationwide evidence covering all stroke subtypes remains limited. We evaluated 10-year secular trends in acute stroke care and outcomes in South Korea using a mandatory national quality audit dataset. Methods:Data from the Acute Stroke Quality Assessment Program, covering nearly all general and tertiary hospitals in Korea, were linked with national insurance claims and mortality records. We analyzed 136,191 episodes of ischemic stroke (IS), intracerebral hemorrhage (ICH), and subarachnoid hemorrhage (SAH) from 2013 to 2023. Results:Over the decade, mean patient age increased (67.1 to 69.6 years), with the ≥85-year population doubling (7.2% to 13.4%). An unexplained discrepancy between ambulance use and arrival time emerged: ambulance use rose (55.4% to 61.8%), but median onset-to-arrival time remained stagnant (4.0 hours), with only 36.6% of IS patients arriving within 3 hours. While intravenous thrombolysis utilization remained stable at approximately 6.0% after 2014, endovascular thrombectomy rates more than doubled (5.3% to 11.6%), reaching 41.1% in severe cases. Statin (92.1%), non-vitamin K antagonist oral anticoagulant (78.4%), and dual antiplatelet therapy (67.2%) use increased markedly. In SAH, treatment shifted from clipping (36.7% to 12.2%) to coiling (36.0% to 63.4%). Notably, adjusted mortality exhibited a non-linear U-shaped trend, reaching a nadir in 2018 followed by an uptick after 2020. Conclusions:Despite substantial improvements in inpatient stroke care, the discrepancy between ambulance use and arrival time highlights structural challenges. Furthermore, the U-shaped mortality reversal underscores the vulnerability of healthcare resilience in a super-aging society, particularly under the strain of the COVID-19 pandemic.
Background and Purpose:The optimal prehospital transport strategy for patients eligible for mechanical thrombectomy remains debated. We evaluated how direct versus secondary transfer to a comprehensive stroke center (CSC) influences outcomes in a large metropolitan stroke network. Methods:This prospective registry-based cohort study included all patients undergoing thrombectomy between 2015 and 2022 in a city of 1.7 million inhabitants. The network comprised 11 primary stroke centers (PSCs) referring to a single CSC, all reachable within 60 minutes. Among 2,017 patients, 242 (12.0%) were transported directly to the CSC, whereas 1,775 (88.0%) were secondarily transferred after initial assessment at a PSC. Functional outcome was assessed using the modified Rankin Scale (mRS) at 90 days. Multivariable logistic and Cox regression models were used to identify independent predictors of good functional outcome and survival. Results:The median onset-to-CSC admission time was shorter after direct versus secondary transfer (101 [7-1,071] vs. 240 [40-1,411] min, P<0.001). A good functional outcome (mRS 0-2) was more frequent after direct transport (50.3% vs. 40.5%, P=0.015). After adjustment for age, National Institutes of Health Stroke Scale score, thrombolysis, posterior circulation stroke, and comorbidities, direct transport independently predicted good functional outcome (odds ratio: 1.74; 95% confidence interval [CI] 1.25-2.42; P=0.001). Among patients receiving combined thrombolysis and thrombectomy (n=1,110), direct transport was associated with improved long-term survival (log-rank P=0.026; adjusted hazard ratio: 0.67; 95% CI 0.47-0.95; P=0.026). Conclusions:Even within a metropolitan network with 1-hour access, direct transport to a CSC shortens treatment delays, improves functional recovery, and enhances survival among patients undergoing combined reperfusion therapy.
Acute brain injury (ABI) affects up to one-third of patients using mechanical circulatory support (MCS). In venoarterial extracorporeal membrane oxygenation (VA ECMO), ABI incidence (11%–40%) has not improved in two decades. Conversely, improvements in left ventricular assist devices (LVADs) have reduced the incidence of stroke, although it remains a major complication (10%–30%). The failure of MCS to ensure adequate cerebral protection may impair cerebrovascular autoregulation (CVAR) and disrupt microcirculatory function affected by reduced pulsatility, endothelial injury, acute perturbations in partial pressure of arterial carbon dioxide (PaCO2), and cerebral venous congestion. Here, we review evidence demonstrating that these factors alter microcirculatory dynamics and CVAR, thereby contributing to ABI through shared mechanistic pathways. Current methods for assessing CVAR are reviewed, including invasive indices such as the pressure reactivity index (PRx) from intracranial pressure monitoring and noninvasive metrics such as the cerebral oximetry index (COx) from near-infrared spectroscopy or flow-velocity correlations from transcranial Doppler. Each method is limited by feasibility, signal artifacts, and inter-modality variability. Our review identifies three priority areas for cerebral protection in MCS: preservation of pulse pressure, cautious titration of PaCO2, and integration of CVAR-informed blood pressure management. Preliminary evidence suggests that very low pulse pressure, rapid carbon dioxide correction, and persistent microcirculatory impairment are each associated with ABI risk. Future investigations should focus on validating bedside tools to assess CVAR and microcirculatory integrity, and on determining whether physiological targets derived from these measures can improve neurological outcomes in patients using MCS.
Background and Purpose Type 2 diabetes (T2DM) is associated with elevated stroke risk. Physical activity may attenuate this excess risk, but large-scale population evidence is limited. This study evaluated whether physical activity mitigates excess stroke risk in individuals with T2DM compared with age- and sex-matched individuals without diabetes. Methods All adults with T2DM registered in the Swedish National Diabetes Register between 2010 and 2019 were included and matched 1:3 to individuals without diabetes based on age and sex. Participants were stratified into five groups according to physical activity. Stroke incidence was estimated using Kaplan–Meier curves, and Cox proportional hazards models calculated adjusted hazard ratios (HRs) for ischemic and hemorrhagic stroke. Robustness was assessed using competing risks regression. Results The cohort included 369,704 individuals with T2DM (mean [standard deviation] age, 64.3 [12.3] years; 156,729 female individuals [42.4%]) and 1,109,112 matched individuals without diabetes. The adjusted HR for ischemic stroke in inactive individuals with T2DM compared with individuals without diabetes was 1.36 (95% confidence interval [CI] 1.23–1.50), declining with higher activity and becoming non-significant among those active ≥3 times/week (HR 1.05, 95% CI 0.96–1.15). The elevated ischemic stroke risk at higher glycated hemoglobin levels was attenuated in individuals with higher physical activity. Conclusions Higher physical activity levels were associated with reduced stroke risk in individuals with T2DM. Those active at least three times weekly had stroke risk comparable to individuals without diabetes of the same age and sex. Promoting physical activity should be an integral component of diabetes care and stroke prevention.
Background and Purpose In patients with large vessel occlusion (LVO), intravenous thrombolysis (IVT) frequently alters thrombus location; however, the clinical impact of this phenomenon remains unclear. We aimed to compare post-IVT thrombus dynamics between tenecteplase and alteplase and to evaluate the association between thrombus dynamics and 3-month outcomes. Methods This retrospective study analyzed prospectively collected, multicenter data from consecutive patients with LVO who underwent bridging therapy between January 2022 and December 2024. Thrombus dynamics were classified as resolution, migration, or stability. Analyses incorporated propensity score matching with weighting to balance baseline characteristics. Results Of the 806 initially included patients, 746 were included after matching (373 treated with tenecteplase and 373 treated with alteplase). The incidence of thrombus migration was significantly higher in the tenecteplase group than in the alteplase group (19.3% vs. 11.3%; odds ratio [OR]: 1.92; 95% confidence interval [CI] 1.27–2.91). The advantage of tenecteplase over alteplase was restricted to patients with an IVT-to-puncture time of <60 minutes (18.6% vs. 6.2%; P=0.001) and was no longer significant when the interval ≥60 minutes (19.7% vs. 15.0%; P=0.204; Pinteraction=0.043). Additionally, thrombus migration was associated with a better functional outcome (OR: 1.62; 95% CI 1.04–2.53). Finally, tenecteplase was associated with improved functional independence compared with alteplase (OR: 1.43; 95% CI 1.04–1.95). Conclusions Tenecteplase demonstrated superior efficacy in inducing thrombus migration compared with alteplase, particularly within 60 minutes of IVT administration. Thrombus migration independently predicted improved functional independence. These findings support the preferential use of tenecteplase for bridging therapy in patients with LVO.
Background and Purpose:Vertebrobasilar fusiform aneurysms (VBFAs) carry substantial morbidity and mortality, but optimal management for unruptured VBFAs remains unclear. We compared the safety and efficacy of conservative management (CM), stent-assisted coiling (SAC), and flow diverters (FDs) in patients with unruptured VBFAs, focusing on long-term prognosis. Methods:This study included data from a nationwide Chinese cohort of patients with vertebrobasilar dissecting aneurysms. Inverse probability of treatment weighting (IPTW) balanced confounders across groups. The primary outcome was poor prognosis (modified Rankin Scale score >2). Secondary outcomes included aneurysm rupture, ischemic stroke, compression symptoms, and VBFA-related deaths. Logistic regression estimated odds ratios (ORs) and 95% confidence intervals (CIs). Subgroup and sensitivity analyses were performed. Results:Among 1,115 patients with unruptured VBFAs, 838 (median age, 54 years; 655 men) were included. After IPTW, baseline characteristics were balanced. Median follow-up was 54 months. FD was associated with a lower risk of poor prognosis than CM (OR, 0.48 [95% CI, 0.30 to 0.77]; P=0.002), with no difference between CM and SAC. FD also reduced aneurysm rupture (OR, 0.20 [95% CI, 0.07 to 0.60]; P=0.004) and compression symptoms (OR, 0.30 [95% CI, 0.13 to 0.68]; P=0.004) versus CM. Time-to-event analyses further revealed significant differences in vertebral artery lesions and Type I-II VBFAs, whereas no significant differences were observed in basilar or vertebrobasilar junction lesions or in Type III-IV VBFAs. Conclusions:Compared with CM, FD was associated with improved long-term outcomes in unruptured VBFAs, particularly in vertebral artery lesions and Type I-II VBFAs, although residual confounding cannot be excluded.
Endovascular thrombectomy for acute large-vessel occlusion in patients with active cancer remains a difficult clinical decision. Multiple cohort studies and meta-analyses indicate that, when standard imaging and clinical criteria are applied, reperfusion success is high and symptomatic intracranial hemorrhage is broadly comparable with non-cancer populations, arguing against categorical exclusion. At the same time, registries show lower 90-day functional independence and higher 90-day mortality in active-cancer cohorts—effects likely driven by malignancy-related systemic factors and pre-existing functional compromise rather than procedural harm. This narrative review synthesizes efficacy and safety signals, highlights decision-grade outcomes that are seldom reported—early neurological change, performance status around 90 days, and whether systemic anticancer therapy is started or resumed. It sets out a clinical–ethical–economic framework to support selection, consent, and aftercare, including a pragmatic pathway for under-resourced settings based on non-contrast computed tomography (CT) or single-phase CT angiography where advanced perfusion imaging or magnetic resonance imaging are unavailable. We outline an Asia–Pacific collaborative program designed to identify subgroups that may benefit from reperfusion and initiation of active cancer care.
Background and Purpose We aimed to evaluate whether early versus late initiation of direct oral anticoagulant (DOAC) after acute ischemic stroke (AIS) yields different safety and efficacy outcomes in Asian versus non-Asian patients. Methods We analyzed Early versus Late initiation of direct oral Anticoagulants in post-ischaemic stroke patients with atrial fibrillatioN (ELAN) trial data from 2,013 AIS patients with atrial fibrillation (AF) randomized to early (≤48 hours for minor/moderate stroke, 6–7 days for major stroke) or late DOAC initiation (3–4 days for minor ischemic stroke, 6–7 days for moderate ischemic stroke, 12–14 days for major ischemic stroke). Patients were categorized by region as Asian (Japan and India) or non-Asian. The primary outcome was a composite of major extracranial bleeding, symptomatic intracranial hemorrhage (SICH), recurrent ischemic stroke, systemic embolism (SE), or vascular death at 30 days (trial registration: ClinicalTrials.gov number, NCT03148457). Results Among 1,975 patients, 245 were Asian (192 from Japan and 53 from India) and 1,730 were non-Asian. The primary outcome occurred in 6.5% of Asian patients (4.8% early vs. 8.3% late) and 3.1% of non-Asian patients (2.7% vs. 3.6%) (P<0.01). Higher rates of recurrent ischemic stroke (4.1% [2.4% vs. 5.8%] vs. 1.7% [1.3% vs. 2.1%], P=0.02) and SE (2.0% [0.8% vs. 3.3%] vs. 0.5% [0.4% vs. 0.6%], P=0.02) accounted for this difference. No significant differences were observed in major extracranial bleeding, SICH, recurrent ischemic stroke, SE, or vascular death. No significant interaction was observed between region and treatment allocation. Conclusions Although Asian patients had worse baseline profiles and outcomes, treatment effects did not differ by region, supporting the generalizability of early DOAC initiation in Asian AIS patients without region-specific timing modifications.
Background and Purpose Patients with ischemic stroke with both atrial fibrillation (AF) and large artery atherosclerosis (LAA) represent therapeutic challenges, and the optimal antithrombotic regimen remains uncertain. We conducted a meta-analysis comparing oral anticoagulant (OAC) monotherapy with OAC plus antiplatelet therapy in this population. Methods PubMed and EMBASE were searched through June 30, 2025, for studies enrolling patients with ischemic stroke and evidence of both AF and LAA. Outcomes included recurrent ischemic stroke, major bleeding, all-cause mortality, and a composite outcome. Pooled odds ratios (ORs) with 95% confidence intervals (CIs) were calculated using the Peto method, with random-effects sensitivity analyses, stratified by short-term (<3 months) and long-term (≥1 year) follow-up. Results Eight cohort studies were analyzed. In the short-term, combination therapy was associated with a reduced risk of recurrent ischemic stroke (OR, 0.37; 95% CI, 0.14–0.97; P=0.043), without a significant increase in major bleeding, although this association did not persist under random-effects sensitivity analysis (OR, 0.37; 95% CI, 0.13–1.07; P=0.067). Conversely, long-term combination therapy was associated with higher risks of major bleeding (OR, 1.25; 95% CI, 1.08–1.45; P=0.002), all-cause mortality (OR, 1.25; 95% CI, 1.01–1.54; P=0.039), and composite outcome (OR, 1.49; 95% CI, 1.27–1.74; P<0.001), without reducing recurrent ischemic stroke (OR, 1.12; 95% CI, 1.00–1.26; P=0.054). Conclusions While long-term OAC plus antiplatelet therapy increases bleeding risk without preventing recurrent stroke, short-term combination therapy may offer benefits in selected patients with concomitant LAA, though this early efficacy signal should be interpreted with caution.
Background and Purpose The relationship between thrombus histology and long-term stroke patient outcomes remains unexplored. We aimed to determine whether the histological characteristics of thrombi are associated with long-term outcomes in stroke patients and to identify the thrombus features linked to these outcomes. Methods This retrospective multicenter cohort study included 512 patients with ischemic stroke who underwent endovascular thrombectomy between July 2017 and July 2023. Patients were followed up for long-term major adverse cardiovascular events occurrence. Thrombus histology was assessed using immunohistochemistry, including the proportion of fibrin, red blood cells, and platelets, as well as the distribution patterns categorized as layered, erythrocytic, diffuse platelet, and mixed. Results During a median follow-up of 38.1 months, 164 patients experienced major adverse cardiovascular events, with an incidence rate of 3.02 per 100 person-years. Major adverse cardiovascular events occurrence was associated with the diffuse platelet pattern and proportion of platelets and red blood cells within the thrombus. After adjusting for confounders, the diffuse platelet pattern independently predicted major adverse cardiovascular events, including mortality and stroke recurrence. Subgroup analysis also demonstrated that the association between the diffuse platelet pattern and major adverse cardiovascular events was consistent across key clinical subgroups based on age (≥65 vs. <65 yr), atrial fibrillation, cancer status, and discharge medications. Conclusions Thrombus histology could provide predictive value for long-term prognosis. In particular, histological distribution patterns may be more important than simple composition in thrombus research, including in the prediction of prognosis.
Background and Purpose To investigate the association between derivatives of reactive oxygen metabolites (d-ROMs), biological antioxidant potential (BAP) and the risk of stroke by subtype, and ischemic heart disease (IHD). Methods We employed a case cohort design consisting of cardiovascular disease cases (n=1,521; stroke, n=1,271; IHD, n=265) and a random sub-cohort (n=4,761) in a large Japanese population-based study. d-ROMs and BAP were measured in plasma samples collected between 1995 and 1999. Hazard ratios (HRs) were estimated using weighted Cox proportional hazards methods according to d-ROMs and BAP quartiles, adjusted for age, sex, area, and potential confounding factors. Results Analysis revealed a positive association between d-ROMs and the risk of total stroke, ischemic stroke, IHD, and the composite outcome of ischemic stroke and IHD. The multivariable HRs and 95% confidence intervals (CIs) for the highest versus lowest quartiles for d-ROMs were 1.34 (95% CI: 1.11–1.63) for total stroke (P for trend<0.001), 1.47 (1.16–1.86) for ischemic stroke (P for trend<0.001), 1.47 (1.02–2.11) for IHD (P for trend=0.072), 1.47 (0.87–2.49) for subarachnoid hemorrhage (P for trend=0.101), and 1.01 (0.72–1.41) for intraparenchymal hemorrhage (P for trend=0.618). In contrast, no significant association was detected between BAP levels and the risk of cardiovascular disease. Conclusions Analysis revealed that d-ROMs levels were positively associated with the risk of ischemic stroke and heart disease but not with hemorrhagic stroke.
Patients with atrial fibrillation who experience acute ischemic stroke (AIS) are at high risk of early recurrent ischemic stroke or systemic embolism. Timely initiation of anticoagulation is essential to prevent subsequent ischemic events but must be carefully balanced against the risk of hemorrhagic transformation or intracranial hemorrhage. Historically, early anticoagulation therapy with heparin or vitamin K antagonists for AIS has shown uncertain benefits. The safety and efficacy of early initiation of non-vitamin K oral anticoagulants, initially suggested by observational studies, have been confirmed by randomized controlled trials and further supported by an individual patient data meta-analysis. However, uncertainties remain in specific populations, including those with severe stroke, hemorrhagic transformation, and Asian patients, who are at an increased risk of intracranial bleeding and are underrepresented in clinical trials.
Background and Purpose:Although gastrointestinal (GI) surgery can affect drug efficacy, its impact on oral anticoagulants (OACs) remains unclear. This study investigated the impact of GI surgery on the comparative effectiveness and safety of direct oral anticoagulants (DOACs) versus warfarin in atrial fibrillation (AF). Methods:Using a nationwide South Korean claims database, AF patients prescribed OACs between 2015 and 2021 were analyzed. The primary outcome was ischemic stroke, and secondary outcomes were major bleeding, all-cause death, and composite outcome (ischemic stroke, major bleeding, all-cause death). Outcomes were compared by OAC type (DOAC vs. warfarin) and GI surgery status using inverse probability of treatment weighting and a Fine-Gray subdistribution hazard model with time-varying covariates. Results:Among 388,214 AF patients (mean age, 71.9 yr; 42.7% male), 6,907 (1.8%) underwent GI surgery. The effect of GI surgery differed between warfarin and DOACs for ischemic stroke (Pint= 0.018), with increased risk for warfarin (adjusted HR [aHR]: 2.32; 95% confidence interval [CI] 1.17-4.62), but not for DOACs (aHR: 0.97 [95% CI 0.77-1.22]) after surgery. Effects of surgery on major bleeding, all-cause death, and composite outcome did not differ. In post-GI surgery setting, DOACs demonstrated lower ischemic stroke risk (aHR: 0.35 [95% CI 0.17-0.72]) and comparable risks for other outcomes. Exploratory analyses by surgery location suggested a more favorable profile of DOACs after upper GI surgery. Conclusions:In AF patients, GI surgery significantly increased ischemic stroke risk among warfarin users, but not among DOAC users. DOACs showed generally favorable profiles after GI surgery and may remain a reasonable anticoagulant, with potentially more favorable profile after upper GI surgery.
