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Randomized trials in stroke often focus on outcomes beyond a single clinical event. Trials of stroke prevention commonly use composite outcomes that include multiple components (eg, death, stroke, or myocardial infarction). A major limitation is that all events count equally but may differ markedly in terms of clinical severity. Trials in acute stroke often use ordinal outcomes or scale scores. Limitations include the requirement for statistical assumptions and the difficulty of handling the competing risk of death. We introduce the win ratio as an alternative method. It works by placing components of a composite into a hierarchy, whereby clinically more important outcomes take priority over less important ones. We illustrate how it works using data from 2 major stroke trials: the ICSS (International Carotid Stenting Study, a trial in stroke prevention) and the MR CLEAN (Multicenter Randomized Clinical Trial of Endovascular Treatment for Acute Ischemic Stroke in the Netherlands). Potential benefits of the win ratio approach include the possibility to (1) emphasize the clinically most important outcomes, (2) combine components of different outcome types into a composite (eg, a mixture of time-to-event, continuous, and categorical), and (3) naturally handle the competing risk of death in analyses of quantitative outcomes. The win ratio will be used in the upcoming analysis of the ECST-2 (Second European Carotid Surgery Trial), which has a hierarchical primary outcome of (1) time to perioperative death, fatal stroke, or fatal myocardial infarction (most important); (2) time to nonfatal stroke; (3) time to nonfatal myocardial infarction (excluding silent infarcts); and (4) new silent cerebral infarct on brain imaging (least important). The win ratio provides a useful clinically relevant method for analyzing trial outcomes. It has some advantages over conventional methods, and we recommend its wider application in future stroke trials.

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Background: The influence of atrial fibrillation (AF) and blood pressure (BP) on brain lesions and cognitive function is unclear. We aimed to investigate the association of BP with different types of brain lesions and cognitive decline in patients with AF. Methods: Overall, 1,213 AF patients underwent standardized brain magnetic resonance imaging at baseline and after 2 years, as well as yearly neurocognitive testing. BP was measured at baseline and categorized according to guidelines. New lesions were defined as new or enlarged brain lesions after 2 years. We defined cognitive decline using three different neurocognitive tests. Logistic and Cox regression analyses were performed to examine the associations of BP with new brain lesions and cognitive decline. Results: The mean age was 71 ± 8.4 years, 74% were male and mean BP was 135 ± 18/79 ± 12 mmHg. New ischemic lesions and white matter lesions were found in 5.4% and 18.4%, respectively. After multivariable adjustment, BP was not associated with the presence of new brain lesions after 2 years. There was no association between BP and cognitive decline over a median follow-up of 6 years when using the Montreal Cognitive Assessment or Digit Symbol Substitution Test. However, BP categories were inversely associated with cognitive decline using the Semantic Fluency Test, with the strongest association in patients with hypertension grade 1 [Hazard Ratio (95% Confidence Interval) 0.57(0.42 to 0.77)], compared to patients with optimal BP (p for linear trend: 0.025). Conclusions: In a large cohort of AF patients, there was no association between BP and incidence of brain lesions after 2 years. Also, there was no consistent association between BP and cognitive decline over a follow-up of 6 years. Clinical Trial Registration: https://clinicaltrials.gov/study/NCT02105844, Identifier (NCT02105844).

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BACKGROUND: Acute kidney injury (AKI) as a result of iodinated contrast media (CM) has been linked to CM-induced renal ischemia and toxic effects on endothelial cells (EC). The recombinant human C1 inhibitor (rhC1INH) has been shown to influence EC activation. METHODS: Secondary analysis of 74/77 (96%) participants of a double-blind, randomized, and placebo-controlled study that assessed the effect of rhC1INH on AKI. E-selectin, intercellular adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule (VCAM-1), and CC-chemokin-ligand-5 (CCL5) were determined in frozen blood samples over 48 h and analyzed according to the treatment group and renal outcomes. RESULTS: The mean age was 76.7 years, and 37 patients each received rhC1INH and placebo, respectively. In the entire study population, minor differences in median EC activation markers/CCL5 concentrations during the first 48 h compared to baseline were observed (e.g., E-selectin 27.5 ng/mL at baseline vs. 29.7 ng/mL on day 1, CCL5: 17.7 ng/mL at baseline vs. 32.2 ng/mL on day 2). Absolute changes in ICAM-1/E-selectin concentrations correlated with a higher peak change in urinary NGAL concentrations. However, AKI was not associated with significant changes in EC markers/CCL5. Last, no significant differences in serum concentrations of EC activation markers/CCL5 were evident between the placebo and the rhC1INH group. CONCLUSIONS: CM administration during coronary angiography only mildly activated ECs within the first 48 h, which does not explain subsequent AKI. The administration of rhC1INH was not associated with a reduction of EC activation or CCL5.

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OBJECTIVES: To determine the prevalence and distribution of intracranial vessel occlusion identified on computed tomography (CT) or magnet resonance (MR) angiography and to explore its association with functional outcome in patients with atrial fibrillation (AF) and ischemic stroke. METHODS: Multicenter cohort study enrolling consecutive patients with AF with imaging-confirmed ischemic stroke who underwent CT- or MR-angiography on admission (2014-2022). Multivariable regression was used to explore the association between intracranial vessel occlusion and poor functional outcome (modified Rankin Scale score 3-6) at 90 days. RESULTS: The analysis included 10,164 patients (median age 81.5 years, 47.8% female, median National Institutes of Health Stroke Scale score on admission 6; 14.7% on a vitamin K antagonist [VKA], 27.5% on a direct oral anticoagulant [DOAC], 57.8% not receiving oral anticoagulation). Angiography showed intracranial vessel occlusion in 5,190 patients (51.1%), affecting the anterior cerebral circulation in 87.4%. Overall, 29.2% and 29.4% of patients received thrombolysis and mechanical thrombectomy, respectively. The proportion of patients with poor functional outcome at 90 days was 60.6% and 42.7% in those with and without vessel occlusion, respectively. In multivariable analyses, vessel occlusion was associated with poor functional outcome (adjusted odds ratio [aOR]: 1.95, 95% confidence interval [CI]: 1.71-2.22) with consistent results in subgroups according to oral anticoagulation use (VKA, aOR: 1.98, 95% CI: 1.40-2.80; DOAC, aOR: 2.35, 95% CI: 1.83-3.03; none, aOR: 1.76, 95% CI: 1.49-2.09). INTERPRETATION: Intracranial vessel occlusion is common in patients with AF with ischemic stroke, mainly affects the anterior circulation and is associated with poor functional outcome. ANN NEUROL 2024.

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OBJECTIVES: Sex differences occur in atrial fibrillation (AF), including age at first manifestation, pathophysiology, treatment allocation, complication rates and quality of life. However, optimal doses of cardiovascular pharmacotherapy used in women with AF with or without heart failure (HF) are unclear. We investigated sex-specific associations of beta-blocker and renin-angiotensin system (RAS) inhibitor doses with cardiovascular outcomes in patients with AF or AF with concomitant HF. METHODS: We used data from the prospective Basel Atrial Fibrillation and Swiss Atrial Fibrillation cohorts on patients with AF. The outcome was major adverse cardiovascular events (MACEs), including death, myocardial infarction, stroke, systemic embolisation and HF-related hospitalisation. Predictors of interest were spline (primary analysis) or quartiles (secondary analysis) of beta-blocker or RAS inhibitor dose in per cent of the maximum dose (reference), in interaction with sex. Cox models were adjusted for demographics, comorbidities and comedication. RESULTS: Among 3961 patients (28% women), MACEs occurred in 1113 (28%) patients over a 5-year median follow-up. Distributions of RAS inhibitor and beta-blocker doses were similar in women and men. Cox models revealed no association between beta-blocker dose or RAS inhibitor dose and MACE. In a subgroup of patients with AF and HF, the lowest hazard of MACE was observed in women prescribed 100% of the RAS inhibitor dose. However, there was no association between RAS dose quartiles and MACE. CONCLUSIONS: In this study of patients with AF, doses of beta-blockers and RAS inhibitors did not differ by sex and were not associated with MACE overall.

Assuntos

Antagonistas Adrenérgicos beta , Fibrilação Atrial , Humanos , Fibrilação Atrial/tratamento farmacológico , Fibrilação Atrial/diagnóstico , Fibrilação Atrial/complicações , Feminino , Masculino , Idoso , Estudos Prospectivos , Fatores Sexuais , Antagonistas Adrenérgicos beta/administração & dosagem , Antagonistas Adrenérgicos beta/efeitos adversos , Fatores de Risco , Pessoa de Meia-Idade , Suíça/epidemiologia , Resultado do Tratamento , Seguimentos , Medição de Risco/métodos , Inibidores da Enzima Conversora de Angiotensina/administração & dosagem , Inibidores da Enzima Conversora de Angiotensina/efeitos adversos , Inibidores da Enzima Conversora de Angiotensina/uso terapêutico , Relação Dose-Resposta a Droga , Fatores de Tempo , Insuficiência Cardíaca/diagnóstico , Insuficiência Cardíaca/fisiopatologia , Idoso de 80 Anos ou mais

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INTRODUCTION: There is limited understanding of the pathomechanistic relationship between leptomeningeal collateral formation and ischaemic stroke aetiology. We aimed to assess the association of leptomeningeal collateral status and ischaemic stroke aetiology, using the widely recognised "Trial of Org 10172 in Acute Stroke Treatment" (TOAST) classification categorising strokes into five distinct aetiologies. METHODS: Retrospective study of consecutively admitted adult ischaemic stroke patients at a Swiss stroke centre. Leptomeningeal collateral status was assessed on admission with single-phase CT-angiographies using a validated 4-point score. Patients were categorised into large-artery atherosclerosis (LAA), cardioembolic (CE), small-vessel disease (SVD) and cryptogenic (CG) according to the TOAST classification. We performed ordinal and binary (poor [collaterals filling ≤50% of the occluded territory] vs good [collaterals filling >50% of the occluded territory] collateralisation) logistic regression to evaluate the impact of TOAST aetiology on collateral status. RESULTS: Among 191 patients, LAA patients had better collateral status compared to non-LAA aetiology (LAA: 2 vs CE: 2 vs SVD: 3 vs CG: 2, pLAA vs non-LAA = 0.04). In weighted multivariate logistic regression, LAA and SVD independently predicted better collateral status (binary models [adjusted odds ratio; aOR]: LAA: 3.72 [1.21-11.44] and SVD: 4.19 [1.21-14.52]; ordinal models [adjusted common odds ratio; acOR]: LAA: 2.26 [95% CI: 1.23-4.15] and SVD: 1.94 [1.03-3.66]), while CE predicted worse collateral status (binary models [aOR]: CE: 0.17 [0.07-0.41]; ordinal models [acOR]: CE: 0.24 [0.11-0.51]). CONCLUSION: The aetiology of ischaemic stroke is associated with leptomeningeal collateral status on single-phase CT-angiography, with LAA and SVD predicting better and CE predicting worse collateral status.

Assuntos

Circulação Colateral , AVC Isquêmico , Meninges , Humanos , Estudos Retrospectivos , Masculino , Feminino , Idoso , AVC Isquêmico/complicações , AVC Isquêmico/etiologia , AVC Isquêmico/fisiopatologia , AVC Isquêmico/diagnóstico por imagem , Suíça/epidemiologia , Meninges/irrigação sanguínea , Meninges/diagnóstico por imagem , Meninges/fisiopatologia , Pessoa de Meia-Idade , Angiografia por Tomografia Computadorizada/métodos , Angiografia Cerebral

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BACKGROUND: Electrical cardioversion (ECV) is frequently performed in symptomatic atrial fibrillation. OBJECTIVE: This study aimed to assess the association of ECV with infarcts on brain magnetic resonance imaging (bMRI) and clinical outcomes. METHODS: The Swiss Atrial Fibrillation Cohort Study included 2386 patients; 1731 patients were evaluated by bMRI. ECVs were recorded by questionnaire. Patients were assigned to categories by number of ECVs performed before enrollment (0, 1, ≥2). A bMRI study was conducted at baseline and after 2 years (n = 1227) and analyzed for large noncortical or cortical infarcts and small noncortical infarcts. Clinical outcomes were recorded during follow-up. Associations of ECV and outcome measures were assessed by multivariate analyses. RESULTS: There was no independent association between the number of ECVs and infarct prevalence (large noncortical or cortical infarcts and small noncortical infarcts) on baseline bMRI (ECV 1 vs 0: odds ratio [OR], 0.95 [95% CI, 0.68-1.24]; ECV ≥2 vs 0: OR, 1.04 [0.72-1.44]) or between ECVs performed during follow-up and new infarcts on bMRI at 2 years (OR, 1.46 [0.54-3.31]). ECVs were not associated with overt stroke or transient ischemic attack (ECV 1 vs 0: hazard ratio [HR], 1.36 [0.88-2.10]; ECV ≥2 vs 0: HR, 1.53 [0.94-2.48]), hospitalization for heart failure (ECV 1 vs 0: HR, 1.06 [0.82-1.37]; ECV ≥2 vs 0: HR, 1.03 [0.77-1.38]), or death (ECV 1 vs 0: HR, 0.90 [0.70-1.15]; ECV ≥2 vs 0: HR, 0.91 [0.69-1.20]). CONCLUSION: There was no association between ECV performed before enrollment and cerebral infarcts on baseline bMRI or between ECV performed during follow-up and new infarcts at 2 years. Moreover, ECV was not associated with clinical events.

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BACKGROUND: Atrial fibrillation (AF) is common in patients with heart failure (HF). Real-world data about long-term outcomes and rhythm control interventions use in AF patients with and without HF remain scarce. METHODS: AF patients from two prospective, multicentre studies were classified based on the HF status at baseline into: HF with preserved ejection fraction (HFpEF), HF with reduced or mildly reduced ejection fraction (HFrEF/HFmrEF), and no HF. The prespecified primary outcome was risk of HF hospitalisation. Other outcomes of interest included mortality, cardiovascular events, AF progression, and quality of life. RESULTS: A total of 1265 patients with AF were analysed (mean age 69.6 years, women 27.4%) with a median follow-up of 5.98 years. Patients with HFpEF (n = 126) had a 2.69-fold and patients with HFrEF/HFmrEF (n = 308) had a 2.12-fold increased risk of HF hospitalisation compared to patients without HF (n = 831, p < 0.001). Similar results applied for all-cause and cardiovascular mortality. The risk for AF progression was higher for patients with HFpEF and HFrEF/HFmrEF (6.30 and 6.79 per 100 patient-years, respectively) compared to patients without HF (4.20). The use of rhythm control strategies during follow-up was least in the HFpEF population (4.56 per 100 patient-years) compared to 7.74 in HFrEF/HFmrEF and 8.03 in patients with no HF. With regards to quality of life over time, this was worst among HFpEF patients. CONCLUSIONS: The presence of HFpEF among patients with AF carried a high risk of HF hospitalisations and AF progression, and worse quality of life. Rhythm control interventions were rarely offered to HFpEF patients. These results uncover an unmet need for enhanced therapeutic interventions in patients with AF and HFpEF.

Assuntos

Fibrilação Atrial , Insuficiência Cardíaca , Fenótipo , Humanos , Fibrilação Atrial/epidemiologia , Fibrilação Atrial/fisiopatologia , Fibrilação Atrial/diagnóstico , Feminino , Masculino , Insuficiência Cardíaca/epidemiologia , Insuficiência Cardíaca/fisiopatologia , Insuficiência Cardíaca/diagnóstico , Idoso , Estudos Prospectivos , Prevalência , Pessoa de Meia-Idade , Seguimentos , Volume Sistólico/fisiologia , Hospitalização/tendências , Qualidade de Vida , Idoso de 80 Anos ou mais , Resultado do Tratamento , Progressão da Doença

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Introduction: The patho-psychological mechanisms of persistent postural-perceptual dizziness (PPPD) appear to be very complex, and a multimodal, multidisciplinary approach is suggested for treating patients with PPPD. The aim of this review was to provide a comprehensive overview of non-pharmacological treatments and their comparative effectiveness in patients with PPPD. Methods: Scopus, Web of Science, PsycINFO, Medline, Embase, CINAHL, Cochrane Library and ClinicalTrials.gov were searched in April 2022 with a search update in August 2023. Only randomized controlled trials (RCTs) were included. There was no restrictions regarding publication date. Two reviewers independently identified eligible trials, extracted data, double-checked all extracted information from the included articles and assessed the risk of bias using the Cochrane risk of bias tool. A qualitative synthesis was performed, considering methodological heterogeneity between trials. Finally, an effect size analysis was performed for each treatment comparison. The standardized mean differences (SMD) and their corresponding 95% confidence intervals (95%CI) were calculated for each trial using Review Manager 5.4. Results: Thirteen RCTs (618 patients with moderate or mild dizziness) out of 1,362 references describing seven different non-pharmacological comparisons were selected. Nine trials included patients with PPPD, and four trials included patients with functional dizziness. The trials used different interventions that were classified as: (1) psychotherapeutic interventions (cognitive behavioral therapy, patient education), (2) physiotherapeutic interventions/training (vestibular rehabilitation, optokinetic stimulation), (3) stimulation procedures (vagus nerve stimulation, transcranial direct current stimulation) and (4) device application (visual desensitization using personalized glasses). However, most of the trials investigated the effects of single interventions, rather than multimodal interdisciplinary treatment of patients with PPPD. The SMD for dizziness handicap and severity was between 0.04 and 0.52 in most trials. In one trial using visual desensitization, the SMD was 1.09 (strong effect on the severity of dizziness) and 1.05 (strong effect on dizziness handicap). Discussion: Several individual interventions have shown benefits in the treatment of patients with PPPD with small to moderate effects. However, the multimodal treatment or a combination of vestibular rehabilitation with visual desensitization, cognitive behavioral therapy including patient education, and medication support should be further investigated. Future trials should include a large sample size with severe dizziness, and provide a longer follow-up period. Clinical trial registration: PROSPERO CRD42022320344.

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RATIONALE: Novel therapeutic approaches are needed in stroke recovery. Whether pharmacological therapies are beneficial for enhancing stroke recovery is unclear. Dopamine is a neurotransmitter involved in motor learning, reward, and brain plasticity. Its prodrug levodopa is a promising agent for stroke recovery. AIM AND HYPOTHESIS: To investigate the hypothesis that levodopa, in addition to standardized rehabilitation therapy based on active task training, results in an enhancement of functional recovery in acute ischemic or hemorrhagic stroke patients compared to placebo. DESIGN: ESTREL (Enhancement of Stroke REhabilitation with Levodopa) is a randomized (ratio 1:1), multicenter, placebo-controlled, double-blind, parallel-group superiority trial. PARTICIPANTS: 610 participants (according to sample size calculation) with a clinically meaningful hemiparesis will be enrolled ⩽7 days after stroke onset. Key eligibility criteria include (i) in-hospital-rehabilitation required, (ii) capability to participate in rehabilitation, (iii) previous independence in daily living. INTERVENTION: Levodopa 100 mg/carbidopa 25 mg three times daily, administered for 5 weeks in addition to standardized rehabilitation. The study intervention will be initiated within 7 days after stroke onset. COMPARISON: Matching placebo plus standardized rehabilitation. OUTCOMES: The primary outcome is the between-group difference of the Fugl-Meyer-Motor Assessment (FMMA) total score measured 3 months after randomization. Secondary outcomes include patient-reported health and wellbeing (PROMIS 10 and 29), patient-reported assessment of improvement, Rivermead Mobility Index, modified Rankin Scale, National Institutes of Health Stroke Scale (NIHSS), and as measures of harm: mortality, recurrent stroke, and serious adverse events. CONCLUSION: The ESTREL trial will provide evidence of whether the use of Levodopa in addition to standardized rehabilitation in stroke patients leads to better functional recovery compared to rehabilitation alone.

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Research to improve and expand treatment options for motor impairment after stroke remains an important issue in rehabilitation as the reduced ability to move affected limbs is still a limiting factor in the selection of training content for stroke patients. The combination of action observation and peripheral nerve stimulation is a promising method for inducing increased excitability and plasticity in the primary motor cortex of healthy subjects. In addition, as reported in the literature, the use of action observation and motor imagery in conjunction has an advantage over the use of one or the other alone in terms of the activation of motor-related brain regions. The aim of the pilot study was thus to combine these findings into a multimodal approach and to evaluate the potential impact of the concurrent application of the three methods on dexterity in stroke patients. The paradigm developed accordingly was tested with 10 subacute patients, in whom hand dexterity, thumb-index pinch force and thumb tapping speed were measured for a baseline assessment and directly before and after the single intervention. During the 10-min session, patients were instructed to watch a repetitive thumb-index finger tapping movement displayed on a monitor and to imagine the sensations that would arise from physically performing the same motion. They were also repeatedly electrically stimulated at the wrist on the motorically more affected body side and asked to place their hand behind the monitor for the duration of the session to support integration of the displayed hand into their own body schema. The data provide a first indication of a possible immediate effect of a single application of this procedure on the dexterity in patients after stroke.

Assuntos

Reabilitação do Acidente Vascular Cerebral , Acidente Vascular Cerebral , Humanos , Projetos Piloto , Masculino , Feminino , Pessoa de Meia-Idade , Idoso , Acidente Vascular Cerebral/fisiopatologia , Acidente Vascular Cerebral/terapia , Reabilitação do Acidente Vascular Cerebral/métodos , Córtex Motor/fisiopatologia , Nervos Periféricos/fisiopatologia , Nervos Periféricos/fisiologia , Imagens, Psicoterapia/métodos , Adulto , Destreza Motora/fisiologia , Estimulação Elétrica/métodos

RESUMO

BACKGROUND: Stroke remains one of the most serious complications in atrial fibrillation (AF) patients and has been linked to disturbances of the autonomic nervous system. OBJECTIVE: The purpose of this study was to test the hypothesis that impaired cardiac autonomic function might be associated with an enhanced stroke risk in AF patients. METHODS: A total of 1922 AF patients who were in either sinus rhythm (SR group; n = 1121) or AF (AF group; n = 801) on a 5-minute resting electrocardiographic (ECG) recording were enrolled in the study. Heart rate variability triangular index (HRVI), standard deviation of normal-to-normal intervals, root mean square root of successive differences of normal-to-normal intervals, mean heart rate, 5-minute total power, and power in the high-frequency, low-frequency, and very-low-frequency ranges were calculated. Cox regression models were constructed to examine the association of heart rate variability (HRV) parameters with the composite endpoint of stroke or systemic embolism. RESULTS: Mean age was 71 ± 8 years in the SR group and 75 ± 8 years in the AF group. Thirty-seven patients in the SR group (3.4%) and 60 patients in the AF group (8.0%) experienced a stroke or systemic embolism during follow-up of 5 years. In patients with SR, HRVI <15 was the strongest HRV parameter to be associated with stroke or systemic embolism (hazard ratio 3.04; 95% confidence interval 1.3-7.0; P = .009) after adjustment for multiple confounders. In the AF group, no HRV parameter was found to be associated with the composite endpoint. CONCLUSION: HRVI measured during SR on a single 5-minute ECG recording is independently associated with stroke or systemic embolism in AF patients. HRV analysis in SR may help to improve risk stratification in AF patients.

Assuntos

Fibrilação Atrial , Eletrocardiografia , Frequência Cardíaca , Acidente Vascular Cerebral , Humanos , Fibrilação Atrial/fisiopatologia , Fibrilação Atrial/complicações , Fibrilação Atrial/diagnóstico , Masculino , Frequência Cardíaca/fisiologia , Feminino , Idoso , Acidente Vascular Cerebral/fisiopatologia , Acidente Vascular Cerebral/etiologia , Embolia/fisiopatologia , Embolia/etiologia , Embolia/diagnóstico , Sistema Nervoso Autônomo/fisiopatologia , Fatores de Risco , Seguimentos , Incidência , Estudos Retrospectivos , Medição de Risco/métodos

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Importance: Whether infarct size modifies the treatment effect of early vs late direct oral anticoagulant (DOAC) initiation in people with ischemic stroke and atrial fibrillation is unknown. Objective: To assess whether infarct size modifies the safety and efficacy of early vs late DOAC initiation. Design, Setting, and Participants: Post hoc analysis of participants from the multinational (>100 sites in 15 countries) randomized clinical Early Versus Later Anticoagulation for Stroke With Atrial Fibrillation (ELAN) trial who had (1) acute ischemic stroke, (2) atrial fibrillation, and (3) brain imaging available before randomization. The ELAN trial was conducted between October 2017 and December 2022. Data were analyzed from October to December 2023 for this post hoc analysis. Intervention: Early vs late DOAC initiation after ischemic stroke. Early DOAC initiation was within 48 hours for minor or moderate stroke or on days 6 to 7 for major stroke; late DOAC initiation was on days 3 to 4 for minor stroke, days 6 to 7 for moderate stroke, and days 12 to 14 for major stroke. Main Outcomes and Measures: The primary outcome was a composite of recurrent ischemic stroke, symptomatic intracranial hemorrhage, extracranial bleeding, systemic embolism, or vascular death within 30 days. The outcome was assessed according to infarct size (minor, moderate, or major) using odds ratios and risk differences between treatment arms. Interrater reliability for infarct size between the core laboratory and local raters was assessed, and whether this modified the estimated treatment effects was also examined. Results: A total of 1962 of the original 2013 participants (909 [46.3%] female; median [IQR] age, 77 [70-84] years) were included. The primary outcome occurred in 10 of 371 participants (2.7%) with early DOAC initiation vs 11 of 364 (3.0%) with late DOAC initiation among those with minor stroke (odds ratio [OR], 0.89; 95% CI, 0.38-2.10); in 11 of 388 (2.8%) with early DOAC initiation vs 14 of 392 (3.6%) with late DOAC initiation among those with moderate stroke (OR, 0.80; 95% CI, 0.35-1.74); and in 8 of 219 (3.7%) with early DOAC initiation vs 16 of 228 (7.0%) with late DOAC initiation among those with major stroke (OR, 0.52; 95% CI, 0.21-1.18). The 95% CI for the estimated risk difference of the primary outcome in early anticoagulation was -2.78% to 2.12% for minor stroke, -3.23% to 1.76% for moderate stroke, and -7.49% to 0.81% for major stroke. There was no significant treatment interaction for the primary outcome. For infarct size, interrater reliability was moderate (κ = 0.675; 95% CI, 0.647-0.702) for local vs core laboratory raters and strong (κ = 0.875; 95% CI, 0.855-0.894) between core laboratory raters. Conclusions and Relevance: The treatment effect of early DOAC initiation did not differ in people with minor, moderate, or major stroke assessed by brain imaging. Early treatment was not associated with a higher rate of adverse events, especially symptomatic intracranial hemorrhage, for any infarct size, including major stroke. Trial Registration: ClinicalTrials.gov Identifier: NCT03148457.

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Anticoagulantes , Fibrilação Atrial , AVC Isquêmico , Humanos , Feminino , Masculino , Fibrilação Atrial/tratamento farmacológico , Fibrilação Atrial/complicações , Idoso , AVC Isquêmico/tratamento farmacológico , Anticoagulantes/administração & dosagem , Anticoagulantes/uso terapêutico , Idoso de 80 Anos ou mais , Pessoa de Meia-Idade , Tempo para o Tratamento , Fatores de Tempo

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BACKGROUND: Whether hemorrhagic transformation (HT) modifies the treatment effect of early compared with late initiation of direct oral anticoagulation in people with ischemic stroke and atrial fibrillation is unknown. METHODS: This is a post hoc analysis of the ELAN trial (Early Versus Late Initiation of Direct Oral Anticoagulants in Post-Ischaemic Stroke Patients With Atrial Fibrillation). The primary outcome was a composite of recurrent ischemic stroke, symptomatic intracranial hemorrhage, major extracranial bleeding, systemic embolism, or vascular death within 30 days. Secondary outcomes were the individual components, 30- and 90-day functional outcome. We estimated outcomes based on HT, subclassified as hemorrhagic infarction (HI) or parenchymal hemorrhage (PH) on prerandomization imaging (core laboratory rating) using adjusted risk differences between treatment arms. RESULTS: Overall, 247 of 1970 participants (12.5%) had HT (114 HI 1, 77 HI 2, 34 PH 1, 22 PH 2). For the primary outcome, the estimated adjusted risk difference (early versus late) was -2.2% (95% CI, -7.8% to 3.5%) in people with HT (HI: -4.7% [95% CI, -10.8% to 1.4%]; PH: 6.1% [95% CI, -8.5% to 20.6%]) and -0.9% (95% CI, -2.6% to 0.8%) in people without HT. Numbers of symptomatic intracranial hemorrhage were identical in people with and without HT. With early treatment, the estimated adjusted risk difference for poor 90-day functional outcome (modified Rankin Scale score, 3-6) was 11.5% (95% CI, -0.8% to 23.8%) in participants with HT (HI: 7.4% [95% CI, -6.4% to 21.2%]; PH: 25.1% [95% CI, 0.2% to 50.0%]) and -2.6% (95% CI, -7.1% to 1.8%) in people without HT. CONCLUSIONS: We found no evidence of major treatment effect heterogeneity or safety concerns with early compared with late direct oral anticoagulation initiation in people with and without HT. However, early direct oral anticoagulation initiation may worsen functional outcomes in people with PH. REGISTRATION: URL: http://www.clinicaltrials.gov; Unique identifier: NCT03148457.

Assuntos

Anticoagulantes , Fibrilação Atrial , AVC Isquêmico , Humanos , Fibrilação Atrial/tratamento farmacológico , Fibrilação Atrial/complicações , Masculino , Feminino , Idoso , AVC Isquêmico/tratamento farmacológico , Administração Oral , Anticoagulantes/administração & dosagem , Anticoagulantes/efeitos adversos , Anticoagulantes/uso terapêutico , Idoso de 80 Anos ou mais , Fatores de Tempo , Pessoa de Meia-Idade , Resultado do Tratamento , Hemorragias Intracranianas/induzido quimicamente

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INTRODUCTION: The impact of leptomeningeal collateralization on the efficacy of mechanical thrombectomy (MT) in patients with anterior circulation large vessel occlusion (aLVO) presenting in the 6-24 h time window remains poorly elucidated. PATIENTS AND METHODS: Retrospective multicenter study of aLVO patients presenting between 6 and 24 h after stroke onset who received MT plus Best Medical Treatment (BMT) or BMT alone. Leptomeningeal collateralization was assessed using single-phase computed tomography angiography (grade 0: no filling; grade 1: filling ⩽50%; grade 2: filling >50% but <100%; grade 3: filling 100% of the occluded territory). Inverse probability of treatment weighted ordinal regression was performed to assess the association between treatment and shift of the modified Rankin Scale (mRS) score toward lower categories at 3 months. We used interaction analysis to explore differential treatment effects on functional outcomes (probabilities for each mRS subcategory at 3 months) at different collateral grades. RESULTS: Among 363 included patients, 62% received MT + BMT. Better collateralization was associated with better functional outcomes at 3 months in the BMT alone group (collateral grade 1 vs 0: acOR 5.06, 95% CI 2.33-10.99). MT + BMT was associated with higher odds of favorable functional outcome at 3 months (acOR 1.70, 95% CI 1.11-2.62) which was consistent after adjustment for collateral status (acOR 1.54, 95% CI 1.01-2.35). Regarding treatment effect modification, patients with absent collateralization had higher probabilities for a mRS of 0-4 and a lower mortality at 3 months for the MT + BMT group. DISCUSSION AND CONCLUSION: In the 6-to-24-h time window, aLVO patients with absent leptomeningeal collateralization benefit most from MT + BMT, indicating potential advantages for this group despite their poorer baseline prognosis.

Assuntos

Circulação Colateral , Trombectomia , Humanos , Masculino , Feminino , Idoso , Circulação Colateral/fisiologia , Estudos Retrospectivos , Pessoa de Meia-Idade , Trombectomia/métodos , Resultado do Tratamento , Meninges/irrigação sanguínea , Meninges/diagnóstico por imagem , Tempo para o Tratamento , AVC Isquêmico/terapia , AVC Isquêmico/cirurgia , AVC Isquêmico/diagnóstico por imagem , AVC Isquêmico/fisiopatologia , AVC Isquêmico/mortalidade , Angiografia por Tomografia Computadorizada , Idoso de 80 Anos ou mais

RESUMO

Background: This study aimed to assess if there are sex differences in the functional outcome of intravenous thrombolysis (IVT) among patients with lacunar stroke (LS). Methods: Consecutive patients admitted from 1 January 2014 to 31 January 2020 to hospitals participating in the Swiss Stroke Registry presenting with LS and treated with IVT were included. The study population was then divided into two groups based on patient sex, and a multivariable ordinal logistic regression analysis was performed to uncover sex differences in the modified Rankin Scale (mRS) score at 90 days after stroke. Results: A total of 413 patients with LS were treated with IVT: 177 (42.9%) women and 236 (57.1%) men. Women were older than men (median age 74 years, 25th-75th percentiles 67-84 years versus 70 years, 25th-75th percentiles 60-80 years, value of p 0.001) and, after adjustment for meaningful variables, showed more frequently increased odds of a higher mRS score at 90 days after stroke (adjusted odds ratio 1.49, 95% confidence interval 1.01-2.19, value of p 0.044). Conclusion: This study showed that female sex increased the odds of a worse functional response to IVT in patients with LS. Future studies should further elucidate the mechanisms underlying such sex differences.

RESUMO

OBJECTIVE: Uncertainty remains regarding antithrombotic treatment in cervical artery dissection. This analysis aimed to explore whether certain patient profiles influence the effects of different types of antithrombotic treatment. METHODS: This was a post hoc exploratory analysis based on the per-protocol dataset from TREAT-CAD (NCT02046460), a randomized controlled trial comparing aspirin to anticoagulation in patients with cervical artery dissection. We explored the potential effects of distinct patient profiles on outcomes in participants treated with either aspirin or anticoagulation. Profiles included (1) presenting with ischemia (no/yes), (2) occlusion of the dissected artery (no/yes), (3) early versus delayed treatment start (median), and (4) intracranial extension of the dissection (no/yes). Outcomes included clinical (stroke, major hemorrhage, death) and magnetic resonance imaging outcomes (new ischemic or hemorrhagic brain lesions) and were assessed for each subgroup in separate logistic models without adjustment for multiple testing. RESULTS: All 173 (100%) per-protocol participants were eligible for the analyses. Participants without occlusion had decreased odds of events when treated with anticoagulation (odds ratio [OR] = 0.28, 95% confidence interval [CI] = 0.07-0.86). This effect was more pronounced in participants presenting with cerebral ischemia (n = 118; OR = 0.16, 95% CI = 0.04-0.55). In the latter, those with early treatment (OR = 0.26, 95% CI = 0.07-0.85) or without intracranial extension of the dissection (OR = 0.34, 95% CI = 0.11-0.97) had decreased odds of events when treated with anticoagulation. INTERPRETATION: Anticoagulation might be preferable in patients with cervical artery dissection presenting with ischemia and no occlusion or no intracranial extension of the dissection. These findings need confirmation. ANN NEUROL 2024;95:886-897.

Assuntos

Anticoagulantes , Aspirina , Dissecação da Artéria Vertebral , Humanos , Feminino , Masculino , Pessoa de Meia-Idade , Dissecação da Artéria Vertebral/tratamento farmacológico , Dissecação da Artéria Vertebral/diagnóstico por imagem , Dissecação da Artéria Vertebral/complicações , Aspirina/uso terapêutico , Anticoagulantes/uso terapêutico , Adulto , Fibrinolíticos/uso terapêutico , Idoso , Resultado do Tratamento

RESUMO

AIMS: Direct-acting oral anticoagulants (DOACs) have, to a substantial degree, replaced vitamin K antagonists (VKA) as treatments for stroke prevention in atrial fibrillation (AF) patients. However, evidence on the real-world causal effects of switching patients from VKA to DOAC is lacking. We aimed to assess the empirical incremental cost-effectiveness of switching patients to DOAC compared with maintaining VKA treatment. METHODS: The target trial approach was applied to the prospective observational Swiss-AF cohort, which enrolled 2415 AF patients from 2014 to 2017. Clinical data, healthcare resource utilisation and EQ-5D-based utilities representing quality of life were collected in yearly follow-ups. Health insurance claims were available for 1024 patients (42.4%). Overall survival, quality-of-life, costs from the Swiss statutory health insurance perspective and cost-effectiveness were estimated by emulating a target trial in which patients were randomly assigned to switch to DOAC or maintain VKA treatment. RESULTS: 228 patients switching from VKA to DOAC compared with 563 patients maintaining VKA treatment had no overall survival advantage over a 5-year observation period (HR 0.99, 95% CI 0.45, 1.55). The estimated gain in quality-adjusted life years (QALYs) was 0.003 over the 5-year period at an incremental costs of CHF 23 033 (€ 20 940). The estimated incremental cost-effectiveness ratio was CHF 425 852 (€ 387 138) per QALY gained. CONCLUSIONS: Applying a causal inference method to real-world data, we could not demonstrate switching to DOACs to be cost-effective for AF patients with at least 1 year of VKA treatment. Our estimates align with results from a previous randomised trial.

Assuntos

Fibrilação Atrial , Acidente Vascular Cerebral , Humanos , Acidente Vascular Cerebral/prevenção & controle , Análise Custo-Benefício , Estudos Prospectivos , Qualidade de Vida , Vitamina K , Anticoagulantes/efeitos adversos , Fibrilação Atrial/complicações , Fibrilação Atrial/diagnóstico , Fibrilação Atrial/tratamento farmacológico

RESUMO

BACKGROUND: We investigated outcomes in patients with intracerebral haemorrhage (ICH) according to prior anticoagulation treatment with Vitamin K antagonists (VKAs), direct oral anticoagulants (DOACs) or no anticoagulation. METHODS: This is an individual patient data study combining two prospective national stroke registries from Switzerland and Norway (2013-2019). We included all consecutive patients with ICH from both registries. The main outcomes were favourable functional outcome (modified Rankin Scale 0-2) and mortality at 3 months. RESULTS: Among 11 349 patients with ICH (mean age 73.6 years; 47.6% women), 1491 (13.1%) were taking VKAs and 1205 (10.6%) DOACs (95.2% factor Xa inhibitors). The median percentage of patients on prior anticoagulation was 23.7 (IQR 22.6-25.1) with VKAs decreasing (from 18.3% to 7.6%) and DOACs increasing (from 3.0% to 18.0%) over time. Prior VKA therapy (n=209 (22.3%); adjusted ORs (aOR), 0.64; 95% CI, 0.49 to 0.84) and prior DOAC therapy (n=184 (25.7%); aOR, 0.64; 95% CI, 0.47 to 0.87) were independently associated with lower odds of favourable outcome compared with patients without anticoagulation (n=2037 (38.8%)). Prior VKA therapy (n=720 (49.4%); aOR, 1.71; 95% CI, 1.41 to 2.08) and prior DOAC therapy (n=460 (39.7%); aOR, 1.28; 95% CI, 1.02 to 1.60) were independently associated with higher odds of mortality compared with patients without anticoagulation (n=2512 (30.2%)). CONCLUSIONS: The spectrum of anticoagulation-associated ICH changed over time. Compared with patients without prior anticoagulation, prior VKA treatment and prior DOAC treatment were independently associated with lower odds of favourable outcome and higher odds of mortality at 3 months. Specific reversal agents unavailable during the study period might improve outcomes of DOAC-associated ICH in the future.

RESUMO

BACKGROUND: The majority of stroke survivors experience long-term impairments. Regular physical activity and other lifestyle modifications play an important role in rehabilitation. Outpatient rehabilitation using telemedicine might be suitable to improve functional ability and long-term secondary prevention. The Strokecoach Intervention Program (SIP, Strokecoach GmbH, Cologne, Germany) comprises training, coaching and monitoring with the aim of improving or at least maintaining functional independence and preventing further stroke through more targeted physical activity. The SIP is provided as blended care, which refers to the integrated and coordinated delivery of healthcare services that combines traditional in-person interactions with technology-mediated interventions, optimizing the use of both face-to-face and virtual modalities to enhance patient outcomes. OBJECTIVE: The aim of this study was to evaluate the acceptance of the SIP by the participants and its practical application, as well as to obtain initial indications of effects of the SIP on the basis of patient-related outcome measures, blood pressure measurements and recording of physical activity in parallel with the intervention. METHODS: Data from individuals with stroke participating in the SIP were analyzed retrospectively. Within the SIP, participants received an application-based training program, were instructed to measure their blood pressure daily and to wear an activity tracker (pedometer). During the intervention period of either 6 or 12 weeks, the participants were supported and motivated by a personal coach via a messenger application. The primary outcomes of the analysis were recruitment, acceptance of and satisfaction with the SIP. Secondary outcomes included functional measures, mobility and health-related quality of life. RESULTS: A total of 122 individuals with stroke could be recruited for the SIP. A total of 96 out of 122 were able to start the program (54% female, mean age 54.8 (SD = 13.1), 6.1 (SD = 6.6) years after stroke onset) and 88 completed the SIP. Participants wore the activity tracker on 66% and tracked their blood pressure on 72% of their intervention days. A further analyzed subgroup of 38 participants showed small improvements in patient-reported outcomes such as health-related quality of life (SF-36) with an increase of 12 points in the subdomain mental health, vitality (12.6) and physical functioning (9.1). However, no statistically significant improvements were found in other performance-based measures (Timed Up and Go test, gait speed). CONCLUSIONS: This study showed that a blended therapy approach for stroke survivors with mild to moderate impairments in the chronic phase is feasible and was highly accepted by participants, who benefitted from the additional coaching.