To Örebro University

BACKGROUND: Stroke and acute myocardial infarction (AMI) rank among the leading causes of mortality. Physical activity and exercise are recommended as part of rehabilitation after AMI to prevent cardiovascular events, but the importance for stroke prevention has not been investigated using population-based data.

OBJECTIVES: To determine associations between participation in exercise-based cardiac rehabilitation (EBCR) and self-reported physical activity with the risk of total stroke, ischemic stroke, and intracerebral hemorrhage after AMI.

METHODS: This was a nationwide, double cohort study conducted across all coronary care units in Sweden between 2005 and 2020, combined with registered data from the general population. Participation in EBCR (24 physiotherapist-led sessions over 4 months) and self-reported physical activity were assessed at a median of 55 days (range 28-90) after hospital discharge. Stroke incidence was followed until death or censoring on December 31, 2021.

RESULTS: A total of 86,637 people with AMI (mean age 64.0, SD 9.0 years; 26 % female), and 259,911 (1:3) age, sex, and region of birth matched individuals from the general population were included. Participation in EBCR after AMI was associated with a lower risk of total stroke (adjusted hazard ratio, aHR 0.85; 95 % confidence interval, CI 0.80-0.91) compared to non-participants, as was ≥150 min of physical activity per week (aHR 0.79, 95 % CI 0.75-0.83). Those reporting physical activity 6 days per week after AMI did not have an increased risk of total stroke or ischemic stroke compared to the general population (aHR 1.03, 95 % CI 0.87-1.23; and aHR 1.17, 95 % CI 0.97-1.41), and were at lower risk of intracerebral hemorrhage (aHR 0.59, 95 % CI 0.35-0.98).

CONCLUSIONS: EBCR and higher levels of physical activity are associated with a decreased risk of stroke after AMI. Cardiac rehabilitation programs and regular and physical activity should be promoted after AMI to decrease the burden of stroke. Swedish Ethical Review Authority Registration number: 2021-03645.

Background: Higher socioeconomic status (SES) among people with migraine has been associated with an increased use of triptans, but it is undetermined whether high SES is also associated with dispensation of monoclonal antibodies against calcitonin gene-related peptide (CGRPi), a prophylactic treatment against migraine episodes. Our hypothesis was that higher SES is associated with CGRPi dispensation, although the association is expected to be attenuated in a country that generally allows for reimbursement of CGRPi costs.

Methods: In this register-based nested case-control study, the association between SES, categorized into three levels (low, middle and high) and the outcome of a first dispensation of a CGRPi was assessed among people with a migraine diagnosis in Region Stockholm, using univariable and multivariable logistic regression models.

Results: Of 52,996 individuals in the study population, 3.2% (n = 1674) were dispensed CGRPi. Individuals with high or middle SES had an increased probability of being dispensed CGRPi, compared to individuals with low SES (adjusted odds ratio = 1.68; 95% confidence interval = 1.46-1.92 and adjusted odds ratio = 1.41; 95% confidence interval = 1.24-1.61, respectively).

Conclusions: Higher SES was associated with dispensation of CGRPi, which suggests unequal access to CGRPi.

BACKGROUND: Intravitreal Anti-Vascular Endothelial Growth Factor (VEGF) rescues retinal vasculatures and prevents disease progression in patients with neovascular Age-Related Macular Degeneration (nAMD). However, systemic anti-VEGF may increase the risk of thromboembolic related complications including stroke and TIA. This study aims to explore the association between stroke and intravitreal anti-VEGF agents; ranibizumab, aflibercept and bevacizumab.

METHODS: This nationwide, population- registry-based case-control study used registered data 2007-2019. Data from the Swedish Stroke Registry (Riksstroke) and the Swedish Macula Register (SMR) were cross-linked to identify nAMD patients who developed stroke/TIA within 90 days after intravitreal anti-VEGF injection. Each stroke case was matched with three controls from Riksstroke with stroke/TIA but no anti-VEGF treatment.

RESULTS: A total of 33 585 patients with nAMD underwent intravitreal anti-VEGF agent injections. A stroke occurred in 1693 patients of this group, and 936 of them within 90 days of treatment. Compared with nonuse, intravitreal anti-VEGF agent use was associated with an increased risk of stroke within 90 days of anti-VEGF treatment in 2.9% of the nAMD-patients [Risk Ratio (RR) 1.27, 95% confidence interval (CI) 1.22; 1.33] compared to non-users. The RR within 30, 31-60 and 61-90 days were 1.36 (1.15; 1.66), 1.40 (1.09; 1.79) and 0.58 (0.52; 0.65), respectively.

CONCLUSIONS: Even though the risk is small, intravitreal injections with anti-VEGF agents for the treatment of nAMD are associated with an increased risk of stroke/TIA. The risk seems to be higher within 60 days of last injection. An assessment of high-risk populations and risk-benefit weighting is necessary before intravitreal anti-VEGF injections are considered.

INTRODUCTION: Endovascular thrombectomy (EVT) is a significant improvement in the care of acute ischemic stroke (AIS) patients, but only a small portion of patients receive treatment. Our aim was to analyze EVT implementation in Sweden according to a set of key performance indicators (KPIs) for procedural and implementational effectiveness.

METHODS: A nationwide prospective registry-based observational study using data from 2018, 2020, and 2022 from the Swedish quality registries for stroke care (Riksstroke and EVAS) and official population statistics. Effectiveness was analyzed using a set of predefined KPIs. To describe procedural and implementation effectiveness in a single comprehensible measure population success rate was derived by multiplying the EVT rate with successful recanalization.

RESULTS: Between 2018 and 2022 EVTs in Sweden increased from 874 to 1474 procedures per year. Correspondingly, the EVT rate (EVT/AIS) increased from 4.1% to 7.3%. Implementation was heterogenous with a six-fold difference between the highest and lowest regions. EVT rates were generally highest in regions with comprehensive stroke centers (CSCs). Procedural effectiveness were similar between all CSCs. The population success-rate increased from 3.4% to 6.4% during the period with large differences between CSCs (range 3.4%-12.4%, in 2022).

CONCLUSIONS: By including KPIs for procedural and implementational effectiveness, it is possible to evaluate EVT implementation for the entire stroke population, which is the ultimate objective for healthcare. The population success-rate is capturing procedural implementation effectiveness in a single measure comprehensible for all stake holders and facilitate comparisons over time and between regions, even between regions with different stroke incidence.

INTRODUCTION: Little is known of the long-term prognosis of patients with acute ischaemic stroke in the absence of standard modifiable stroke risk factors (SMoRFs). In acute coronary syndromes, patients without modifiable risk factors have a higher mortality rate. We analysed data from the Swedish Stroke Register to determine survival of patients without SMoRFs following an ischaemic stroke.

PATIENTS AND METHODS: We identified adult patients with first-presentation acute ischaemic stroke between 2010 and 2020. Patients were considered to possess a SMoRF if they had one of: hypertension, diabetes, hyperlipidaemia, atrial fibrillation or an active smoking history. We compared mortality in patients with and without SMoRFs following first-presentation ischaemic stroke using cox regression models. We also assessed the combined endpoint death and dependency (mRS 3-6) at 3 months via logistic regression models.

RESULTS: Of 152,588 patients with ischaemic stroke, hypertension (58.7%) and atrial fibrillation (27.3%) were the most common risk factors. 34,019 patients (22.3%) had no SMoRFs. After a first-presentation ischaemic stroke, patients without SMoRFs had a lower risk of death than patients with one or more SMoRFs (HR 0.58 [95% CI 0.57-0.59]). The absence of SMoRFs was associated with lower odds of death and dependency at 3 months in logistic regression models (OR 0·60 [95% CI 0.58-0.62]).

CONCLUSION: One in five patients with acute ischaemic stroke had no standard modifiable stroke risk factors. These patients have lower risk of death compared to patients with one or more SMoRFs.

INTRODUCTION: Reversal treatment is commonly used for managing oral anticoagulant (OAC)-associated intracranial haemorrhages. Its effects on mortality are still understudied, particularly in various subtypes of intracranial haemorrhages. This systematic review and meta-analysis aims to synthesise the available data to study the impact of reversal therapies on mortality following various OAC-associated acute intracranial haemorrhages.

METHODS AND ANALYSIS: This protocol follows the Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) Protocols, and the final review will be reported in accordance with the PRISMA reporting guidelines. This systematic review and meta-analysis will include studies that assess contemporary reversal treatment in comparison to no reversal treatment, in cases of OAC-associated intracranial haemorrhage. Stratification will be performed for the types of bleeding as well as OAC at bleeding onset. Preliminary searches to determine search term inclusions were conducted in May-August 2024 in the electronic databases Embase, PubMed, Scopus and Web of Science without language and publication date restrictions. Randomised controlled studies, non-randomised controlled trials, and observational studies will be considered for the final meta-analysis. Three reviewers (MT, JOS and AB) will screen titles and abstracts, and one reviewer (MT) will subsequently conduct full-text screening. Risks of bias will be assessed by MT using tools such as Risk of Bias 2, Risk Of Bias In Non-randomised Studies - of Interventions and the Newcastle-Ottawa Scale. Heterogeneity among the study results will be assessed using the I² statistic. If appropriate, a random-effects meta-analysis model will be performed. Subgroup analyses and meta-regression (if applicable) will be performed to assess sources of heterogeneity among (1) intracranial haemorrhage types, (2) OAC drugs and (3) study types, with randomised controlled trials being the primary focus.

ETHICS AND DISSEMINATION: Ethical approval is not needed as this project involves previously published data. We intend to publish the results in a peer-reviewed journal.

PROSPERO REGISTRATION NUMBER: CRD42024556420.

BACKGROUND AND OBJECTIVES: Diabetes significantly increases the risk of cardiovascular events, including stroke. Although the association with ischemic stroke is well established, the relationship with hemorrhagic stroke remains unclear. This study aimed to evaluate the risk of ischemic and hemorrhagic stroke in individuals with type 1 and type 2 diabetes compared with diabetes-free controls from the general population.

METHODS: This cohort study included individuals with type 1 or type 2 diabetes from the Swedish National Diabetes Register between 2005 and 2019, matched to diabetes-free controls by age and sex. Data on baseline characteristics, comorbidities, medications, and outcomes were collected from multiple national registers. Stroke incidence rates and adjusted hazard ratios were estimated using Cox proportional hazard models, stratified by diabetes type, for ischemic and hemorrhagic stroke.

RESULTS: The study included 47,720 individuals with type 1 diabetes (mean age 34.4, 44.8% female) and 686,158 with type 2 diabetes (mean age 65.3, 43.3% female), matched to 143,160 and 2,058,474 controls, respectively. In individuals with type 1 diabetes, the ischemic stroke risk was 2.54 times higher (95% CI 2.36-2.73) and the hemorrhagic stroke risk was 1.88 times higher (95% CI 1.57-2.26) compared with controls. In individuals with type 2 diabetes, the ischemic stroke risk was 1.37 times higher (95% CI 1.35-1.38) while the hemorrhagic stroke risk was not significantly increased (HR: 0.99, 95% CI 0.96-1.02). Higher HbA1c levels were associated with increased ischemic stroke risk for both diabetes types. For hemorrhagic stroke, individuals with type 1 diabetes had significantly higher risk starting at HbA1c > 52 mmol/mol while in those with type 2 diabetes, a modest risk increase was observed only at HbA1c > 72 mmol/mol.

DISCUSSION: The risk of ischemic stroke was higher for both diabetes types. Individuals with type 1 diabetes also exhibited a higher risk of hemorrhagic stroke compared with diabetes-free controls while type 2 diabetes was significantly associated with risk of hemorrhagic stroke only when HbA1c was higher than 72 mmol/mol. These findings highlight the increased stroke risk in diabetes, with distinct patterns by stroke subtype and diabetes type. Tailored prevention strategies are essential to address these differences.

BACKGROUND: A rapid shift has occurred from vitamin K antagonists toward direct oral anticoagulants, which have a lower risk of intracerebral hemorrhage (ICH). However, effects on clinical outcomes after ICH are understudied. We aimed to describe the prevalence of antithrombotic drugs and to study the prognosis among prestroke functionally independent Swedish patients with ICH.

METHODS AND RESULTS: We identified all patients diagnosed with nontraumatic ICH in 2017 to 2021 from the Swedish Stroke Register (n=13 155) and assessed death and functional outcome at 3 months after ICH in prestroke functionally independent patients (n=10 014). Functional outcome was estimated among 3-month survivors on the basis of self-reported activities of daily living scores. Risks of outcomes were estimated using Poisson regression. In 13 155 patients, 14.5% used direct oral anticoagulant, 10.1% vitamin K antagonists, and 21.6% antiplatelets at ICH onset. Among 10 014 pre-stroke activities of daily living-independent patients, oral anticoagulants and antiplatelets were associated with increased mortality risk (adjusted risk ratio, 1.27 [95% CI, 1.13-1.43]; P<0.001; and adjusted risk ratio, 1.23 [95% CI, 1.13-1.34]; P<0.001 respectively). Mortality risk did not statistically differ between antiplatelets and oral anticoagulants nor between direct oral anticoagulant and vitamin K antagonists. Among 5126 patients with nonmissing functional outcome (69.1% of survivors), antiplatelets (adjusted risk ratio, 1.06 [95% CI, 0.99-1.13]; P=0.100) and oral anticoagulants (adjusted risk ratio, 1.01 [95% CI, 0.92-1.12]; P=0.768) were not statistically significantly associated with functional dependence.

CONCLUSIONS: There was no statistically significant difference in mortality risk between direct oral anticoagulant and vitamin K antagonists in prestroke functionally independent patients (unadjusted for oral anticoagulant class indication). Furthermore, mortality risk in antiplatelet and oral anticoagulant users might differ less than previously suggested.

Early identification of stroke symptoms is essential. The rate of stroke identification by call-takers at emergency medical communication centres (EMCCs) varies, and patients who are found in a lying down position are often not identified as having an ongoing stroke.

OBJECTIVES: this study aimed to explore signs and symptoms of stroke in patients who had fallen or were found in a lying position.

DESIGN: a retrospective exploratory qualitative study design was used.

METHOD: a total of 29 emergency calls to EMCCs regarding patients discharged with a stroke diagnosis from a large teaching hospital in Stockholm, Sweden, in January-June 2011, were analysed using qualitative content analysis.

RESULTS: during the emergency calls, the callers described a sudden change in the patient's health status including signs such as the patient's loss of bodily control, the patient's perception of a change in sensory perception, and the callers' inability to communicate with the patient.

CONCLUSIONS: The callers' descriptions of stroke in a person found in a lying position are not always as described in assessment protocols describing the onset of a stroke. Instead, the symptom descriptions are much vaguer. Therefore, to increase identification of stroke during emergency calls, there is a need for an increased understanding of how callers describe stroke symptoms and communicate with the call-takers.

PURPOSE: To perform a meta-analysis on how the admissions of stroke and transient ischemic attack (TIA) changed during the Corona Virus infection-19 (COVID-19) pandemic and evaluate if the effect was depending on stroke severity.

METHODS: Observational cohort studies comparing the number of stroke and/or TIA admissions during a period of the pandemic compared to a period before the pandemic were identified in PubMed and Embase. After excluding studies with overlapping populations and studies without satisfactory case ascertainment, data was extracted and meta-analyzed.

FINDINGS: A total of 59 studies were included. During the pandemic, there was a decrease in admissions of ischemic stroke (admission rate ratio (ARR) = 0.77, 95% confidence interval (CI): 0.72, 0.82), intracerebral hemorrhage (ARR = 0.79, 95% CI: 0.70, 0.90) and TIA (ARR = 0.66, 95% CI: 0.58, 0.75). Albeit admission rates of both mild (ARR = 0.61, 95% CI: 0.49, 0.77) and severe (ARR = 0.82, 95% CI = 0.71, 0.95) strokes decreased, milder strokes decreased more (proportion ratio (PR) = 0.76, 95% CI: 0.65, 0.89).

DISCUSSION: Potential causes for the admission reduction could be strict prioritizations within the health care, patients' fear of acquiring COVID-19, or decreased access to health care due to lockdowns.

CONCLUSION: During the COVID-19 pandemic, there was a reduction in admissions of stroke and TIA, possibly caused by reluctance to seek medical care.