International Journal of Stroke最新文献

Background: Rinvecalinase alfa (DM199), a recombinant form of human tissue kallikrein-1 (KLK1), aims to promote local vasodilation to ischemic brain and enhance collateral blood flow. The ReMEDy1 trial tested the safety and tolerability of rinvecalinase alfa in ischemic stroke.

Methods: ReMEDy1 was a phase II, randomized, double-blind, placebo-controlled, study conducted at 13 Australian sites. Ninety-two patients with NIH Stroke Scale (NIHSS) 6-25 were enrolled within 24 h of ischemic stroke onset. Patients were randomized 1:1 to receive rinvecalinase alfa (1 µg/kg intravenous infusion followed by 3 µg/kg subcutaneously every 3 days for 22 days) or placebo. The primary outcome was safety, assessed by adverse events (AEs) and serious adverse events (SAEs). Secondary outcomes included changes in NIHSS, modified Rankin Scale (mRS), and Barthel Index (BI) at Days 22 and 90. Post hoc analyses excluded patients who underwent endovascular therapy (EVT).

Results: The median age was 72, NIHSS 10, and onset-to-randomization was 19.5 h. SAEs were reported in 20/47 (43.5%) rinvecalinase alfa patients and 14/45 (31.1%) placebo patients. Most patients experienced at least one AE; the most common in the rinvecalinase alfa group were constipation (60.9%), oral candidiasis (23.9%), and nausea (17.4%). Stroke-in-evolution by Day 90 occurred in 0 (0%) rinvecalinase alfa patients versus 6 (13.3%) placebo patients; 4/6 (66.7%) placebo patients with stroke-in-evolution died. No significant differences were observed in secondary efficacy outcomes at Day 90. Post hoc analyses in patients not treated with EVT suggested a tendency toward improved excellent global outcomes with rinvecalinase alfa.

Conclusions: Rinvecalinase alfa appeared to be safe and generally well-tolerated in ischemic stroke patients, with potential efficacy in reducing stroke progression. Further studies are needed to confirm efficacy and long-term benefits in patients without EVT.

Registrations: https://www.

Clinicaltrials: gov/study/NCT03290560.

Background: This study aims to evaluate the efficacy and safety of dual antiplatelet therapy (DAPT) versus single antiplatelet therapy (SAPT) for patients with a first-ever embolic stroke of undetermined source (ESUS).

Methods: We assembled a multicenter cohort and a propensity score-matched (PSM) subset to compare DAPT with SAPT. The primary outcome was a composite of recurrent ischemic stroke, myocardial infarction, or all-cause death, and the safety outcome was major bleeding. Follow-up extended to 3 years (median, 2.6 years). We used Cox proportional hazards models to complement time-stratified (piecewise) analyses and restricted mean survival time (RMST).

Results: In the total cohort (n = 1675), DAPT was associated with a lower hazard of the composite outcome (adjusted hazard ratio (HR) = 0.56, 95% confidence interval (CI) = 0.44-0.70). Stroke recurrence and mortality were likewise reduced, while myocardial infarction events were infrequent. There was no significant difference in major bleeding between groups (e.g. incidence-rate ratio ≈1.0; p > 0.05). The annual incidence rate for the composite was 5.5%/year with DAPT versus 10.1%/year with SAPT. Time-stratified analyses revealed that the ischemic benefit was most pronounced between 6 and 12 months and appeared to persist thereafter. Bleeding, however, showed only a numerical increase beyond 1 year without statistical significance. RMST differences favored DAPT from 1 year onward and increased over 1000 days.

Conclusion: In this ESUS cohort, DAPT was associated with fewer ischemic events and no increased major bleeding. The benefit was most evident at 6-12 months and was sustained over a longer follow-up period.

Background: Frailty is a dynamic predictor of adverse stroke outcomes, but its bidirectional relationship with stroke-how frailty progresses before and after stroke-remains underexplored.

Aims: This study aims to examine longitudinal frailty index (FI) trajectories in individuals with and without stroke, and changes in frailty trajectories within individuals before and after a stroke event across four international longitudinal studies.

Methods: This prospective cohort study analyzed data from four longitudinal cohorts: China Health and Retirement Longitudinal Study (CHARLS), English Longitudinal Study of Ageing (ELSA), Health and Retirement Study (HRS), and Survey of Health, Ageing and Retirement in Europe (SHARE). Frailty progression was assessed using validated FI scores. Incident strokes were identified through self-reported doctor diagnoses. Linear mixed models were used to evaluate changes in FI before and after stroke.

Results: Among the 73,961 participants, 4374 (5.9%) incident stroke events were identified. Compared to stroke-free individuals, stroke survivors exhibited an observable increase in FI prior to the stroke event (e.g.

Charls: β = 0.016/year, 95% confidence interval (CI): 0.014-0.017). A sharp increase in FI occurred during the incident stroke event (HRS: β = 0.078, 95% CI: 0.074-0.083), followed by sustained post-stroke acceleration (ELSA: β = 0.019/year, 95% CI: 0.016-0.022). Sensitivity analyses confirmed robustness across cohorts.

Conclusion: Frailty accelerates significantly both before and after an incident stroke, suggesting a bidirectional relationship between stroke and frailty. Integrating frailty assessment into stroke risk stratification, rehabilitation, and secondary prevention to optimize patient outcomes, particularly in aging populations.Data access statement:The datasets generated and analyzed during the current study are available on the HRS website (https://hrs.isr.umich.edu/), CHARLS (https://charls.pku.edu.cn/en), SHARE (https://share-eric.eu/), and ELSA (https://www.elsa-project).

Background: The relationship between cannabis use and stroke prevalence remains incompletely characterized, with most studies limited by binary exposure classification. We examined the frequency-dependent association of cannabis use and stroke prevalence by subtype in a large, diverse national cohort.

Aims: Our primary aim was to explore the relationship between cannabis use frequency and the adjusted prevalence of ischemic and hemorrhagic stroke.

Methods: We conducted a cross-sectional analysis of 122,767 adults from the National Institutes of Health (NIH) All of Us Research Program who completed lifestyle surveys between 2017-2022. Cannabis use frequency was stratified into five categories: never, once or twice, monthly, weekly, and daily. Ischemic and hemorrhagic stroke diagnoses were identified using International Classification of Diseases (ICD) 9 and 10 codes. Multivariable logistic regression models were adjusted for age, sex, race/ethnicity, obesity, type 2 diabetes, alcohol, and tobacco use.

Results: Among 122,767 participants, 2,765 (2.3%) had a history of stroke. After multivariable adjustment, a significant frequency-dependent association was found for ischemic stroke; compared to never-users, "once or twice" use was associated with a 10% increased odds (adjusted odds ratio (aOR) = 1.10, confidence interval (CI) = 0.95-1.26), monthly use with a 3% reduced odds (aOR = 0.97, CI = 0.73-1.29), weekly use with a 45% increased odds (aOR = 1.45, 95% CI = 1.19-1.77), and daily use with a 48% increased odds (aOR = 1.48, 95% CI = 1.26-1.74). In contrast, the odds of hemorrhagic stroke were elevated across all frequencies of cannabis use, with the highest odds observed in monthly users (aOR = 1.74, 95% CI = 1.21-2.51). These subtype-specific associations contributed to an overall increased odds of any stroke for weekly (aOR = 1.39) and daily (aOR = 1.44) users.

Conclusions: In this large, nationally representative study, cannabis use was associated with stroke through two distinct, subtype-specific patterns. Odds of ischemic stroke demonstrated a clear dose-response relationship concentrated among frequent (weekly or daily) users, while odds of hemorrhagic stroke were elevated across all frequencies of use. These findings highlight the need to incorporate detailed cannabis use assessment into routine cerebrovascular risk stratification.

Background: Stroke is associated with an increased risk of dementia, but the temporal dynamics of dementia risk before and after stroke diagnosis remain uncertain. This study aimed to examine the risk of dementia from 10 years before through 30 years after stroke diagnosis, compared with non-stroke individuals.

Methods: We performed a case-control study using the UK Biobank data. We identified all participants diagnosed with stroke who had disease occurrence data available in the database. Controls were matched 3:1 for year of birth, sex, and education level. Conditional logistic regression was applied to estimate odds ratios (ORs) for incident dementia across different time windows before and after stroke diagnosis.

Results: This study included 24,056 individuals with stroke and 74,136 matched controls. The risk of dementia was higher in individuals with stroke compared to non-stroke controls in each time window before stroke diagnosis, with ORs ranging from 1.43 (95% confidence interval (CI): 1.02-2.01, p = 0.040) in 5-10 years before diagnosis to 5.11 (95% CI: 4.06-6.41, p < 0.001) in 1 year immediately before stroke. Within the first year after stroke diagnosis, the risk of incident dementia was the highest (OR: 6.39, 95% CI: 5.20-7.87, p < 0.001). Similar results have been observed across sexes and different age groups.

Conclusions: Participants who developed stroke had a higher risk of dementia beginning a decade before stroke onset, with risk peaking in the year around the diagnosis of stroke. These findings suggest the importance of prevention strategies at much earlier stages in individuals who are at risk of developing stroke and dementia.

Objective: To validate whether incorporating existing polygenic risk scores (PRSs) derived from East Asian or trans-ancestry populations into clinical risk equations improves stroke risk stratification in Chinese adults.

Methods: Participants from the Chinese Multi-provincial Cohort study with genotyped data (n = 2931) were included. Four well-established PRSs (i.e., PRS-GBMI, PRS-GIGA, PRS-ChinaPAR, and PRS-MEGA) from either the predominantly Chinese or trans-ancestry populations were constructed and evaluated by assessing their associations with stroke and its subtypes. We tested the incremental predictive capability of the four PRSs for the 10- and 20-year risk of stroke and its subtypes after adding PRSs to recalibrated China-PAR stroke risk equations, based on discrimination, calibration, and reclassification.

Results: Over a median follow-up period of 28.2 years, 340 stroke events were recorded. Higher PRSs were generally associated with a higher stroke risk, though only the highest quantile group of PRS-GIGA showed statistical significance (hazard ratio (HR): 1.79, 95% confidence interval (CI): 1.05-3.07). Adding PRS-GIGA to the recalibrated China-PAR stroke risk equations (i.e., the base model) yielded a moderate improvement in 20-year stroke risk, with 17.2% (95% CI: 3.8%-30.6%) more participants correctly categorized into their corresponding risk groups. However, for ischemic stroke, adding PRS-GIGA, PRS-ChinaPAR, and PRS-MEGA to the base model could correctly categorize 18.7%-23.8% more participants into their corresponding 10-year risk groups and 27.8%-32.5% more participants into their corresponding 20-year risk groups. Adding PRSs did not improve prediction for hemorrhagic stroke.

Conclusion: Adding existing PRSs, particularly PRS-GIGA, to clinical risk equations can improve all stroke and ischemic stroke risk stratification in Chinese adults.

Background: Although long-term stroke management is critically important, poor patient adherence to follow-up appointments threatens the validity of clinical trials. This cross-sectional survey aimed to identify contributing factors and potential consequences of lost to follow-up (LTFU) in long-term stroke management trials.

Methods: We searched Medline, Embase, Web of Science, Cochrane library, and Scopus from inception to 20 August 2024 for randomized controlled trials of multimodal post-stroke care initiated within 1 year of stroke. Data on general trial and methodological characteristics were extracted. Univariable random-effects meta-regression analyses were performed to identify LTFU predictors. Furthermore, we assessed how assumptions about LTFU affected effect estimates for significant binary primary outcomes.

Results: Among 58 eligible reports (27,575 patients and 3349 caregivers), six trials (10.3%) did not specify patient LTFU, while 8 of 17 caregiver-inclusive trials (47.1%) omitted LTFU reporting of caregivers. The median follow-up was 12 months (interquartile range (IQR): 6-12), with LTFU rates of 9.0% (IQR: 3.2-15.4%) for patients and 14.0% (IQR: 6.8-20.7%) for caregivers. Higher LTFU odds correlated with a higher proportion of females (odds ratio (OR): 2.93, 95% confidence interval (CI): 1.30-9.29) and older age (OR: 3.05, 95% CI: 1.38-9.07). Trials involving multidisciplinary rehabilitation teams showed lower LTFU (OR: 0.05, 95% CI: 0.01-0.26). When assuming different event rates for LTFU patients, 0-14.3% of significant results were no longer significant.

Conclusion: Overall, approximately 10% of stroke trials on long-term patient management still did not report LTFU. Identified potential risk factors may provide targets to improve the continuity of stroke management within these trial settings. Attention to patient management is critical for ensuring valid trial conclusions.

Background: Mobile stroke units (MSUs) improve outcomes in acute ischemic stroke (AIS), but their effectiveness is constrained by limited service radii. Integrating a rendezvous strategy with emergency medical services (EMS) may extend the operational reach of MSUs in rural areas.

Aim: We evaluated whether a novel rendezvous approach between MSUs and EMS could enhance thrombolysis efficiency for rural AIS patients in a larger service area.

Methods: We conducted a single-center, pragmatic, non-randomized, operationally allocated comparative study in Suzhou, Anhui, from 1 January to 31 December 2024. When a suspected stroke call originated from a remote location, a nearby conventional ambulance was dispatched. Subsequently, the MSU was dispatched via an EMS call, met the EMS at a predetermined midway point en route to the stroke center, and treated the patient when MSU was available. Inclusion criteria were: age ⩾ 18 years; onset location ⩾ 20 km from the MSU center; and onset-to-call time ⩽ 4 h. Patients with a final diagnosis of cerebral ischemia were analyzed based on transport method (MSU rendezvous vs EMS only). The primary outcome was the thrombolysis rate; secondary outcomes included time metrics, 90-day functional prognosis, and incidence of symptomatic intracranial hemorrhage (sICH). Propensity score matching (PSM) was used to balance baseline characteristics.

Results: A total of 307 patients with AIS were included; the median age was 72 years (IQR, 63-79), and 192 (62.50%) were male. One hundred ninety-three patients were transferred through rendezvous transport, and 114 patients were transferred through EMS-only. The median distance from onset location to hospital in the rendezvous transport group was 39.00 km (24.23 miles) (IQR 30.00-47.00 km), with a maximum of 68.00 km (42.25 miles). Compared with EMS-only transfers, patients transferred through rendezvous transport had a nearly 3-fold increase in thrombolysis rates (68.90% vs 17.50%, p < 0.001), reduced dispatch-to-door time by 12.5 min, door-to-needle time by 46 min, and onset-to-needle time by 60 min (all p < 0.001). In addition, in terms of clinical outcomes, patients in the rendezvous group had lower median 90-day modified Rankin Scale scores (2.0 (1.0-3.0) vs 3.0 (1.5-5.0), p < 0.001). These findings remained consistent after PSM.

Conclusion: Our study demonstrates that the novel MSU-EMS rendezvous approach significantly improves thrombolysis rates and functional outcomes, serving as a viable strategy to expand acute stroke care to remote populations.Data access statement:Data collected for the study may be made available from the corresponding author to others upon reasonable request.