Patients with noncardioembolic ischemic stroke or transient ischemic attack (TIA) are at risk for recurrent stroke. Low factor XI levels are associated with a reduced risk of ischemic stroke. Asundexian inhibits activated factor XI. Whether the addition of asundexian to antiplatelet therapy would be superior to antiplatelet therapy alone for the secondary prevention of ischemic stroke is unclear. In this phase 3, double-blind trial, we randomly assigned patients within 72 hours after the onset of a noncardioembolic ischemic stroke or high-risk TIA to receive asundexian (50 mg once daily) or placebo, in addition to planned dual or single antiplatelet therapy. Patients had at least one of the following: a nonlacunar infarct on imaging, a history of atherosclerosis, or evidence of atherosclerotic plaque at any location on cerebrovascular imaging. The primary efficacy outcome was ischemic stroke. The composite of death from cardiovascular causes, myocardial infarction, or stroke was a key secondary outcome. The primary safety outcome was major bleeding. Among 12,327 patients who underwent randomization (6162 to the asundexian group and 6165 to the placebo group), the incidence of ischemic stroke was lower in the asundexian group than in the placebo group (6.2% vs. 8.4%; cause-specific hazard ratio, 0.74; 95% confidence interval [CI], 0.65 to 0.84; P<0.001). The incidence of the composite of death from cardiovascular causes, myocardial infarction, or stroke was lower in the asundexian group than in the placebo group. The incidence of major bleeding was similar in the asundexian group and the placebo group (1.9% and 1.7%, respectively; cause-specific hazard ratio, 1.10; 95% CI, 0.85 to 1.44). The incidence of adverse events was 69.3% in the asundexian group and 70.1% in the placebo group; the incidence of serious adverse events was 19.2% and 19.5%, respectively. Among patients with noncardioembolic ischemic stroke or high-risk TIA treated with antiplatelet therapy, asundexian at a daily dose of 50 mg resulted in lower risks of ischemic stroke and major cardiovascular events than placebo, without a higher risk of major bleeding. (Funded by Bayer; OCEANIC-STROKE ClinicalTrials.gov number, NCT05686070.).

Background: Health state utility values are commonly used to provide summary measures of health‐related quality of life in studies of stroke. Contemporaneous summaries are needed as a benchmark to contextualize future observational studies and inform the effectiveness of interventions aimed at improving post‐stroke quality of life. Methods and Results: We conducted a systematic search of the literature using Medline, EMBASE, and Web of Science from January 1995 until October 2020 using search terms for stroke, health‐related quality of life, and indirect health utility metrics. We calculated pooled estimates of health utility values for EQ‐5D‐3L, EQ‐5D‐5L, AQoL, HUI2, HUI3, 15D, and SF‐6D using random effects models. For the EQ‐5D‐3L we conducted stratified meta‐analyses and meta‐regression by key subgroups. We screened 14 251 abstracts and 111 studies met our inclusion criteria (sample size range 11 to 12 447). EQ‐5D‐3L was reported in 78% of studies (study n=87; patient n=56 976). The pooled estimate for EQ‐5D‐3L at ≥3 months following stroke was 0.65 (95% CI, 0.63–0.67), which was ≈20% below population norms. There was high heterogeneity (I ² >90%) between studies, and estimates differed by study size, case definition of stroke, and country of study. Women, older individuals, those with hemorrhagic stroke, and patients prior to discharge had lower pooled EQ‐5D‐3L estimates. Conclusions: Pooled estimates of health utility for stroke survivors were substantially below population averages. We provide reference values for health utility in stroke to support future clinical and economic studies and identify subgroups with lower healthy utility. Registration: URL: https://www.crd.york.ac.uk/prospero/ . Unique Identifier: CRD42020215942.

Background and Purpose: The association between physical activity (PA) and lower risk of stroke is well established, but the relationship between leisure sedentary time and stroke is less well studied. Methods: We used 9 years of the Canadian Community Health Survey between 2000 and 2012 to create a cohort of healthy individuals without prior stroke, heart disease, or cancer. We linked to hospital records to determine subsequent hospitalization or emergency department visit for stroke until December 31, 2017. We quantified the association between self-reported leisure sedentary time (categorized as <4, 4 to <6, 6 to <8, and 8+ hours/day) and risk of stroke using Cox regression models and competing risk regression, assessing for modification by PA, age, and sex and adjusting for demographic, vascular, and social factors. Results: There were 143 180 people in our cohort and 2965 stroke events in follow-up. Median time from survey response to stroke was 5.6 years. There was a 3-way interaction between leisure sedentary time, PA, and age. The risk of stroke with 8+ hours of sedentary time was significantly elevated only among individuals <60 years of age who were in the lowest PA quartile (fully adjusted hazard ratio, 4.50 [95% CI, 1.64–12.3]). The association was significant across multiple sensitivity analyses, including adjustment for mood disorders and when accounting for the competing risk of death. Conclusions: Excess leisure sedentary time of 8+ hours/day is associated with increased risk of long-term stroke among individuals <60 years of age with low PA. These findings support efforts to enhance PA and reduce sedentary time in younger individuals.

Recovery trajectories in intracerebral hemorrhage (ICH) are recognized as distinct from those observed in ischemic stroke. This narrative review aims to clarify the pathophysiology underlying ICH recovery patterns, highlighting the unique timeline and nature of functional improvements seen in ICH survivors. Population-based cohort studies tracking functional outcomes in a longitudinal fashion, along with randomized clinical trial data with standardized outcome assessments, have demonstrated that ICH recovery generally has a delayed onset in the first weeks, followed by a steep early subacute stage recovery (typically up to 3 months) continuing in protracted, gradual improvements beyond 3 to 6 months. Understanding these recovery patterns, and how these differ from ischemic stroke, is crucial for providing accurate prognostic information, facilitating targeted health care delivery, and optimizing therapeutic interventions and the design of ICH randomized trials. This article synthesizes current evidence on early- and late-stage functional recovery trajectories in primary, spontaneous ICH and cognitive outcomes, emphasizing the clinical and research implications of these recovery patterns.

Background: Although age-standardized stroke occurrence has been decreasing, the absolute number of stroke events globally, and in Canada, is increasing. Stroke surveillance is necessary for health services planning, informing research design, and public health messaging. We used administrative data to estimate the number of stroke events resulting in hospital or emergency department presentation across Canada in the 2017–18 fiscal year.Methods: Hospitalization data were obtained from the Canadian Institute for Health Information (CIHI) Discharge Abstract Database and the Ministry of Health and Social Services in Quebec. Emergency department data were obtained from the CIHI National Ambulatory Care Reporting System (Alberta and Ontario). Stroke events were identified using ICD-10 coding. Data were linked into episodes of care to account for readmissions and interfacility transfers. Projections for emergency department visits for provinces/territories outside of Alberta and Ontario were generated based upon age and sex-standardized estimates from Alberta and Ontario.Results: In the 2017–18 fiscal year, there were 108,707 stroke events resulting in hospital or emergency department presentation across the country. This was made up of 54,357 events resulting in hospital admission and 54,350 events resulting in only emergency department presentation. The events resulting in only emergency department presentation consisted of 25,941 events observed in Alberta and Ontario and a projection of 28,409 events across the rest of the country.Conclusions: We estimate a stroke event resulting in hospital or emergency department presentation occurs every 5 minutes in Canada.

Survivors of stroke are at high risk of dementia, but it is unclear whether this elevated risk is due to other confounding factors. We sought to determine the magnitude and time course of dementia risk after stroke with robust comparison with matched nonstroke populations in an entire province. We conducted a population-wide analysis of over 15 million people in Ontario, Canada, between 2002 and 2022. Using linked administrative databases, we identified adults hospitalized for ischemic stroke, intracerebral hemorrhage, or acute myocardial infarction (AMI). We performed 1:1 matching of people with stroke to all residents of Ontario (reference population) without stroke and separately to those with AMI, on age, sex, rural residence, neighborhood deprivation, and vascular comorbidities. We calculated the incident rate per 100 person-years and hazard ratios (HRs) for all-cause dementia between 90 days after stroke and 1 year, 5 years, 10 years, and total follow-up and evaluated time-varying HRs. In sensitivity analyses, we adjusted for new stroke in follow-up and the cumulative number of health care encounters. Of 175,980 stroke survivors, 174,817 (99.3%) were successfully matched to people in the reference population and 151,673 (90%) were matched to those with AMI. Over a mean follow-up of 5.6 years (SD 4.71, maximum 20 years), a total of 32,621 (18.7%) were diagnosed with dementia after stroke compared with 21,929 (12.5%) in the Ontario reference population. The rate of dementia per 100 person-years over total follow-up time was higher after acute stroke compared with the reference population (3.34 vs 1.89) and the AMI cohort (3.19 vs 1.75). The HR of dementia was higher in those with stroke compared with the reference population (1.76, 95% CI 1.73-1.79) and the AMI cohort (1.82, 1.79-1.85). HRs varied across time, with over 2.5-fold increase in dementia risk within 1 year, decreasing to 1.5-fold at 5 years and 1.3-fold at 20 years after stroke. Estimates were similar in sensitivity analyses. Recurrent stroke was associated with 3-fold increased dementia risk. In this population-wide study, almost one-fifth of stroke survivors were diagnosed with dementia, with an 80% higher risk of dementia after robust matching to those without stroke. Targeted dementia prevention efforts in acute and chronic survivors of stroke are needed.