International Journal of Stroke最新文献

Background: Randomized controlled trials (RCTs) have traditionally been designed with an explanatory approach, in contrast to incorporating real-world, pragmatic considerations.

Aims: This methodological review assesses the uptake of pragmatic designs in Phase III acute stroke RCTs.

Methods: We conducted a comprehensive literature search of the MEDLINE, Embase, and Cochrane Library databases from inception to 1 July 2024. Eligible articles included English-language published Phase III RCTs of acute ischemic stroke and intracerebral hemorrhage interventions. Using the Pragmatic Explanatory Continuum Indicator Summary (PRECIS-2) tool, each trial was rated on nine key domains, and relevant study characteristics were extracted. Trials with an average rating of 3 or higher, or a total score (sum of ratings) of 27 or higher (given that all domains were assessed), were considered to adopt an overall pragmatic approach to their design. Risk of bias was evaluated using the Cochrane risk of bias tool.

Results: Of the 5663 unique articles obtained after deduplication, 136 trials were included, and 71 (52%) trials were classified as pragmatic using the PRECIS-2 tool. A majority had a low risk of bias (63.2%). Pragmatic trials were more likely to be large sample, multicenter, multinational trials with broad inclusion criteria that cover multiple types of strokes.

Conclusion: There has been an increased uptake of pragmatic designs in acute stroke over the last decade, reflecting improvements in acute stroke care and a greater consideration of real-world applicability by trialists.

Introduction: More intensive antiplatelet agents may reduce recurrent stroke risk in minor stroke and TIA, particularly those with non-cardioembolic stroke. The SOCRATES trial showed that ticagrelor was not superior to aspirin in decreasing the risk of stroke, heart attack, or death at 90 days in patients with minor ischemic stroke or TIA. Cilostazol has been shown to have similar effects on platelet reactivity and aggregation to those produced by ticlopidine and aspirin, but may be associated with fewer hemorrhagic side effects. It is also cheaper than ticagrelor; for example, it is approximately half that of ticagrelor, making it a potentially cost-effective antiplatelet agent, especially in low and middle-income countries.

Aim: To evaluate the benefits or hazards of adding cilostazol or ticagrelor to aspirin in patients with minor ischemic stroke or TIA.

Methods: We randomized 900 first-ever, large-vessel occlusion minor ischemic stroke or TIA patients in a one-to-one ratio to receive either a 200 mg loading dose of cilostazol within 24 h after acute stroke symptoms, then 100 mg twice daily until day 90 post-stroke, or a 180 mg loading dose of ticagrelor during the first 24 h, followed by 90 mg twice daily from day 2 to day 90. Both groups received an open-label 300 mg loading dose of aspirin during the first 24 h, then 75 mg once daily. We followed up with our patients for 3 months.

Results: 857 patients completed the 3-month follow-up study 34 (7.6%) patients in the cilostazol group and 29 (6.4%) patients in the ticagrelor group experienced a new stroke (either hemorrhagic or ischemic) (HR 1.37; 95% CI, 0.84-2.26; p-value = 0.21), and 44 (9.8%) patients in the cilostazol group and 40 (8.9%) patients in the ticagrelor group experienced a composite of a new stroke, myocardial infarction (MI), or death due to vascular insults (HR 1.11; 95% CI, 0.64-1.93; p-value = 0.30). Fifteen (3.3%) patients in the cilostazol arm and 30 (6.7%) patients in the ticagrelor arm experienced drug-related hemorrhagic complications (HR 0.32; 95% CI, 0.19-0.68; p-value = 0.01).

Conclusion: Combining cilostazol with aspirin in large-vessel occlusion minor ischemic stroke or TIA was as effective as ticagrelor and aspirin in preventing recurrent stroke, MI, and death due to vascular events, but resulted in significantly lower rates of hemorrhagic complications.

Background: The Colchicine for prevention of vascular inflammation in Non-CardioEmbolic stroke (CONVINCE) trial evaluated long-term treatment with colchicine for the prevention of major adverse cardiovascular events (MACE) in a stroke population. Although the intention-to-treat analysis did not demonstrate a significant reduction in the primary endpoint, fewer outcome events were observed in the colchicine-treated group. It is unknown if a potential treatment effect is modified by ischemic stroke etiology.

Aims: In this pre-specified secondary analysis, we aimed to evaluate the efficacy of colchicine for prevention of MACE in patients with minor stroke or high-risk transient ischemic attack (TIA) according to index event stroke etiology.

Methods: A total of 3154 patients with recent non-cardioembolic stroke or TIA were randomly assigned to receive colchicine, 0.5 mg daily in addition to guideline-based usual care or usual care alone. The primary endpoint was a composite of first fatal or non-fatal recurrent ischemic stroke, myocardial infarction, cardiac arrest, or hospitalization for unstable angina. Subgroups of patients with large-artery atherosclerosis, small-vessel disease, and cryptogenic stroke were evaluated.

Results: A total of 3100 patients were included in the current analysis. The treatment effect did not vary across stroke subtype subgroups (p = 0.64 for interaction). In patients allocated to colchicine versus usual care alone, the primary endpoint occurred in 32 of 260 (12.3%) versus 42 of 263 (16%) patients with large-artery atherosclerosis (hazard ratio (HR), 0.77 (95% CI, 0.48-1.22)); 39 of 419 (9.3%) versus 47 of 435 (10.8%) patients with small-vessel occlusion (HR, 0.87 (95% CI, 0.57-1.34)); and 82 of 877 (9.4%) versus 92 of 846 (10.5%) patients with cryptogenic stroke (HR, 0.89 (95% CI, 0.66-1.12)).

Conclusions: The direction of effect for prevention of recurrent MACE favored colchicine, consistent with randomized trials in coronary disease, regardless of stroke subtype. Future stroke trials should consider selecting patients with evidence of atherosclerosis irrespective of stroke subtype.

Trial registration: ClinicalTrials.gov Identifier: NCT02898610.

Background: Cerebral venous thrombosis (CVT) is a rare but life-threatening condition, particularly among pregnant and postpartum women. However, estimates of its incidence, recurrence, and associated adverse outcomes remain inconsistent. Moreover, the role of antithrombotic prophylaxis in mitigating these risks has not been fully established.

Objective: This study aimed to synthesize global evidence on the incidence of CVT during pregnancy and postpartum, evaluate recurrence rates of CVT and noncerebral venous thromboembolism (VTE), assess adverse pregnancy outcomes, and explore the efficacy and safety of antithrombotic prophylaxis in high-risk populations.

Methods: A systematic review and meta-analysis was conducted following Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Five major databases were searched for observational studies reporting CVT incidence, recurrence, or pregnancy outcomes in women with prior CVT or noncerebral VTE, covering the period from 1980 to September 2024, with an updated search completed on May 6, 2025. Data were pooled using random-effects models and heterogeneity was quantified via the I² statistic.

Results: Forty-seven studies encompassing 14,218 pregnancies were included. The pooled incidence of postpartum CVT was 7 cases per 100,000 deliveries (95% confidence interval [CI]: 3-15), with significant regional disparities (Asia: 19/100,000; Europe: 3/100,000). The recurrence rate of CVT was 10.2 per 1000 deliveries (95% CI: 5-21), while noncerebral VTE recurred in 15.3 per 1000 pregnancies (95% CI: 8-28). The crude risk of spontaneous abortion was 15.7% (95% CI: 13-19), with higher rates observed in women not receiving prophylaxis. Antithrombotic prophylaxis appeared to reduce the risk of noncerebral VTE recurrence but did not significantly affect CVT recurrence.

Conclusions: CVT and noncerebral VTE pose substantial risks during pregnancy, particularly in women with prior thrombotic events. Although antithrombotic prophylaxis may offer partial protection, its benefits must be carefully weighed against potential maternal and fetal risks. These findings underscore the need for individualized management and further research to inform evidence-based clinical guidelines.

Purpose: We aimed to clarify the clinical characteristics and outcomes of patients with in-hospital onset ischemic stroke (IOS) compared with those in patients with community-onset ischemic stroke (COS).

Methods: Patients from the Japan Stroke Data Bank, a hospital-based multicenter prospective registry, who were diagnosed with acute ischemic stroke (AIS) within 24 h of onset between January 2001 and December 2020 were included in this study. We assessed favorable outcomes at discharge corresponding to a modified Rankin Scale (mRS) score of 0-2, unfavorable outcomes corresponding to an mRS score of 5-6, and mortality. We also examined trends in these outcomes at 4-year intervals over a period of 20 years.

Results: Of the 100,865 patients analyzed, 2979 had IOS (1416 women, mean age 77 ± 12 years) and were older than those with COS (n = 97,886; 39,110 women, mean age 74 ± 12 years). Multivariate analysis revealed that younger age, higher premorbid mRS score, absence of stroke history, normotension, congestive heart failure, coronary artery disease, chronic kidney disease, liver disease, malignancy, tendency to bleed, and cardioembolic stroke were positively associated with IOS. Compared with COS, IOS was inversely associated with a favorable outcome (42.1% vs 64.8%, adjusted odds ratio [aOR] 0.72 [95% confidence interval (CI) 0.63-0.82]), positively associated with an unfavorable outcome (mRS 5-6 at discharge; 34.3% vs 15.5%, aOR 1.31 [95% CI 1.16-1.48]), and mortality (11.8% vs 4.6%, aOR 1.59 [95% CI 1.37-1.84]). Over 20 years, the mortality rate significantly decreased in both patients with IOS and COS (p < 0.01 both).

Conclusion: IOS is associated with unfavorable outcomes and higher mortality rates during acute hospitalization. The mortality rates in patients with IOS decreased over time, similar to those observed in patients with COS.

Background: The association between statin use and the risk of incident intracerebral hemorrhage (ICH) remains controversial, with concerns about a potential increased risk of ICH among statin users.

Aims: This study aimed to investigate the association between statin use and incident ICH in the general population.

Methods: This prospective cohort study utilized data from UK Biobank. Cox proportional regression models were employed to estimate hazard ratios (HRs) for the association between statin use and incident ICH in both unmatched and propensity score-matched (PSM) cohorts, adjusting for sociodemographic characteristics, lifestyle factors, comorbidities, and concurrent medication use.

Results: A total of 421,444 participants were included in the final analysis, with a median age of 58.0 years (interquartile range [IQR]: 50.0-63.0), and 53.9% were female. At baseline, 69,272 individuals reported regular statin use. Over a median follow-up period of 12.75 years (IQR: 11.30-14.21), 1533 participants (0.4%) experienced incident ICH. Multivariate Cox regression analyses showed that statin use was significantly associated with a reduced risk of ICH in the fully adjusted model (aHR 0.77; 95% CI 0.66-0.90). This association was significant among individuals without a history of coronary artery disease, stroke or transient ischemic attack (aHR 0.75; 95% CI 0.63-0.89). Potential interaction effects were identified between statin use and age (p for interaction = 0.027 in the total cohort), waist-to-hip ratio, and low-density lipoprotein cholesterol levels (p for interaction = 0.025 and 0.062, respectively, in the PSM cohort) in relation to ICH risk.

Conclusion: In this large population-based study, statin use was associated with a reduced risk of incident ICH, providing further evidence for the long-term safety of statin therapy with respect to ICH risk in the general population and across diverse subgroups.Data access statement:UK Biobank database is available on application by approved researchers.

Background: We recently developed and validated the SMA²SH²ERS risk prediction model for aneurysmal subarachnoid hemorrhage (ASAH) in the general population (c-statistic 0.62; 95% confidence interval [CI] 0.60-0.64). Given that women have higher ASAH incidence than men, and that predictors for ASAH have different effect sizes between sexes, we developed sex-specific risk prediction models.

Methods: Data from the prospective UK Biobank Study were used for model development. Participants with ASAH (per hospital-based ICD codes) before baseline or with missing predictor data were excluded. We developed multivariable Cox proportional hazards models for women and men separately to study the association between earlier recognized SMA²SH²ERS predictors and incident ASAH. Predictive performances were assessed with c-statistics and calibration plots and corrected for overfitting using bootstrapping.

Results: A total of 246,771 women and 210,085 men were included with median follow-up of 12 years. ASAH incidence rate per 100 000 person years was 16.1 in women, and 10.7 in men. The women-specific model had a c-statistic of 0.63 (95% CI 0.60-0.65) and the mean predicted absolute 10-year ASAH risk was 0.15%. Independent predictors for women were higher age, family history of stroke, former and current smoking, alcohol consumption, and intermediate education. The men-specific model c-statistic was 0.57 (95% CI 0.53-0.60) and the mean 10-year risk 0.10%. Independent predictors for men were higher age, hypertension, and smoking status.

Conclusion: The sex-specific models did not perform better than the general SMA²SH²ERS model in women or in men. Further validation studies are needed before clinical use can be recommended.

Background and aims: Unscheduled hospital readmission following stroke is common and has a significant effect on quality of life for patients and their families. However, there is limited evidence on the factors associated with unscheduled hospital readmission time in the first-year post-stroke discharge. This study aims to investigate patient and healthcare system factors associated with unscheduled hospital readmission time in a cohort of first-ever stroke patients in Scotland, UK.

Methods: This is a population-level data-linkage study using data on adult stroke patients admitted to hospital between 2010 and 2018, with follow-up to end of 2019. The association between unscheduled hospital readmission time and patient and healthcare system factors was assessed using multivariable zero-inflated negative binomial estimations.

Results: Among the 48,040 stroke patients (median age 73 years [interquartile range (IQR) 63-82]; 48.7% female) included in the study, 14,794 (30.8%) had at least one unscheduled readmission in the 1-year post-stroke discharge follow-up (median age 76 years [IQR 66-83]; 51.5% female). Median time spent in hospital as an unscheduled readmission in the 1-year follow-up was 9 days [IQR 3-25]. After adjustment, an increased risk of total unscheduled readmission time was associated with increasing age (≥ 80 years versus < 50 years Incidence Rate Ratio (IRR) 2.23 (95% CI 1.96-2.53)); living alone before stroke (IRR 1.17 (95% CI 1.11-1.24)); stroke severity (most versus least severe IRR 1.14 (95% CI 1.04-1.26)); intracerebral hemorrhage (IRR 1.29 (95% CI 1.18-1.42)); higher Charlson Comorbidity Index (CCI) (⩾3 versus 0 IRR 1.17 (95% CI 1.08-1.26)); higher frailty index (severe versus none IRR 1.16 (1.01-1.35); and longer length of stay for initial stroke admission (>10 days IRR 1.28 (95% CI 1.21-1.36)). Reduced risk of unscheduled readmission time was associated with lower socio-economic deprivation (least versus most deprived IRR 0.91 (95% CI 0.83-0.99)); prior transient ischaemic attack (TIA) (IRR 0.85 (95% CI 0.75-0.96)); and receipt of complete stroke care bundle (IRR 0.94 (95% CI 0.88-0.99)).

Conclusion: Increased unscheduled hospital readmission time was associated with several factors including living alone, a higher comorbidity burden, stroke severity, and stroke type. Greater community support for these at-risk patients in terms of living arrangements and more pro-active outpatient management of comorbidities may be needed to reduce unscheduled readmission time following stroke discharge.

Background: A large proportion of early neurological deterioration (END) in stroke due to middle cerebral artery (MCA) stenosis remains unexplained. Unstable plaques on MCA and impaired perforators might contribute to unexplained END.

Methods: We included patients with symptomatic MCA stenosis and classified them into three groups according to symptoms: END, stable, and transient ischemic attack (TIA). High-resolution 7 T vessel wall magnetic resonance imaging (MRI) (VW-MRI) and time-of-flight magnetic resonance (MR) angiography (TOF-MRA) were used to investigate MCA plaque features and lenticulostriate artery (LSA) morphology. We compared demographic data, plaque features and LSA morphology between three groups, and used binary logistic regression models to investigate factors that could potentially be related to END.

Results: Fifty-two patients (49.46 ± 13.94 years, 39 males) were included in final analyses. Patients in three groups did not differ in age or vascular risk factors. Irregular plaque surface (16/16 vs 12/16 vs 11/20 in END vs stable vs TIA groups, P = 0.008) and plaques adjacent to LSA origin (14/16 vs 10/16 vs 7/20, P = 0.006) were more commonly seen in the END group than the other two groups. On TOF-MRA, TIA patients had more LSA branches (6[1,15] vs 5[1,9] vs 7[4,12] in END vs stable vs TIA groups, P = 0.018) and longer total LSA length (95.37 ± 43.98 vs 92.42 ± 33.10 vs 129.61 ± 38.77 mm, P = 0.012). Larger lesion size, higher LDL level and plaques adjacent to LSA origin were significantly associated with END, before and after the adjustment for age and sex.

Conclusion: The 7 T MRA provide precise imaging capabilities for plaque characteristics and LSA in patients with MCA stenosis and END, which could help stratify the risks of END and provide evidence for treatment of ischemic stroke caused by MCA arthrosclerosis.