Stroke Trials Research Articles

Baseline systolic blood pressure and efficacy of dual antiplatelet in acute ischaemic stroke

ObjectiveSystolic blood pressure (SBP) affects the risk of early neurological deterioration (END). This subgroup analysis of Antiplatelet Therapy in Acute Mild to Moderate Ischemic Stroke (ATAMIS) trial aimed to explore...

High plasma thrombomodulin level is associated with a decreased risk of cognitive impairment after ischemic stroke

BackgroundThrombomodulin, a thrombin receptor with anticoagulant, anti-inflammatory, and cytoprotective properties, has been suggested to play a pivotal role in ischemic stroke. However, the association of plasma thrombomodulin with post-stroke cognitive impairment (PSCI) remains unclear. We aimed to prospectively investigate the associations of plasma thrombomodulin with PSCI among ischemic stroke patients in a multicenter cohort study. MethodsWe measured plasma thrombomodulin levels at baseline among 615 ischemic stroke patients from a preplanned ancillary study of the CATIS (China Antihypertensive Trial in Acute Ischemic Stroke). We used Montreal Cognitive Assessment (MoCA) to evaluate cognitive function at 3-month follow-up after ischemic stroke, and PSCI was defined as MoCA score <23. ResultsPlasma thrombomodulin was inversely associated with PSCI, and the adjusted odds ratio of PSCI for the highest versus lowest quartile of thrombomodulin was 0.50 (95% CI: 0.28-0.92, Ptrend=0.026). Each standard deviation increment of log-transformed thrombomodulin was associated with a 23% (odds ratio: 0.77, 95% CI: 0.62-0.97, P=0.029) decreased risk of PSCI. In addition, plasma thrombomodulin could significantly improve the risk reclassification of PSCI beyond established risk factors (net reclassification index: 25.04%, 95% CI: 7.20%-42.87%, P=0.007; integrated discrimination improvement: 1.13%, 95% CI: 0.18%-2.09%, P=0.020). ConclusionsHigh plasma thrombomodulin levels were associated with a decreased risk of PSCI among ischemic stroke patients. Our findings suggest that plasma thrombomodulin might be a predictive biomarker and potential therapeutic target for PSCI.

Consent-Related Outcomes in the Alteplase Compared to Tenecteplase Trial.

In recent years, researchers have sought to address the challenges of obtaining informed consent for participation in acute stroke trials. We studied outcomes related to the use of deferral of consent in the phase 3 Alteplase Compared to Tenecteplase (AcT) trial. As part of our protocol, we captured methods of consent, participant withdrawals, door-to-randomization times, and door-to-needle times. Participants at 3 sites were invited to complete a survey of attitudes regarding consent for AcT and for acute stroke trials generally. The AcT trial enrolled 1,600 participants from 22 centers across Canada of whom 1,537 were enrolled through deferral of consent (96.0%) and 63 (4.0%) were enrolled by prospective verbal consent followed by written informed consent. Of those enrolled by deferral of consent, 95% (1,454/1,537) consented to ongoing participation. Door-to-randomization times were similar regardless of method of consent, with an overall median of 30 minutes (interquartile range [IQR] 22-42): 29 minutes (IQR 22-42) in the deferral of consent group vs 32 minutes (IQR 25-44) in the prospective consent group (p = 0.1602). Survey respondents overwhelming agreed or strongly agreed with the use of deferral of consent in AcT (86%) and in any acute stroke trial (76%). Deferral of consent was broadly acceptable to participants in the AcT trial as demonstrated by low rates of withdrawal and by survey results. Door-to-randomization times using deferral of consent in AcT were short, although a system of prospective verbal consent used at 1 center took only slightly longer. These results support the importance of innovation around consent for acute stroke trials.

Predicting the Prognosis of Stroke Patients Based on Personalized Federated Learning

In recent years, the incidence of stroke has been increasing and showing a trend of younger people. Based on the distributed stroke risk assessment modeling scenario, this paper solves the problems of insufficient data and difficult data sharing in medical institutions through federated learning. Considering the features of structured data, the proposed algorithm takes the non-neural network model as the base model, and combines bagging and gradient boosting algorithms to achieve model updating and aggregation. This paper also proposes the model pruning method to realize the personalization of each participant’s model and reduces the data transmission cost of the algorithms by separating the weight matrix of the model and the model parameters. Experiments show that the proposed method greatly outperforms existing baseline approaches according to the predictive results, and the accuracy of the personalized model and the global model in the International Stroke Trial (IST) dataset reaches 78.20% and 76.85%, respectively, which has broader application scenarios.

Plasma neuropeptide Y levels and adverse clinical outcomes after acute ischaemic stroke.

Neuropeptide Y (NPY) has been reported to be involved in the pathophysiology of several cardiovascular disease processes and might contribute to the incidence of stroke, but the prognostic utility of circulating NPY after acute ischaemic stroke is unclear. This study aimed to prospectively examine the association between plasma NPY levels and adverse clinical outcomes after acute ischaemic stroke. Plasma NPY levels were measured in 3250 patients (2066 men and 1184 women) from the China Antihypertensive Trial in Acute Ischaemic Stroke. The primary outcome was the combination of death and major disability (modified Rankin Scale score ≥3) at 12 months after stroke onset, and secondary outcomes included major disability, death and cardiovascular events. During the 12-month follow-up, 702 participants (21.6%) experienced major disability or died. After multivariable adjustment, odds ratio (95% confidence interval) for the highest quartile of NPY was 1.56 (1.19-2.04) for the primary outcome, compared to the lowest quartile. Each standard deviation (0.27 ng/mL) higher log-transformed NPY was associated with an odds ratio (95% confidence interval) of 1.18 (1.07-1.30) for the primary outcome, 1.28 (1.15-1.42) for major disability. The addition of NPY to a conventional risk factors model improved risk prediction of the composite outcome of death and major disability (category-free net reclassification index 8.82%, p = 0.040; integrated discrimination improvement 0.38%, p = 0.011). Elevated plasma NPY levels in the acute phase of ischaemic stroke were associated with increased risk of poor clinical outcomes after ischaemic stroke, suggesting that plasma NPY may be a potential prognostic biomarker for ischaemic stroke.

Mortality Risk in Patients With Cardiac Complications Following Ischemic Stroke: A Report From the Virtual International Stroke Trials Archive.

Cardiac complications may occur in patients following ischemic stroke (stroke-heart syndrome [SHS]). We investigated the mortality risk in patients with SHS and across the SHS manifestations. Data were sought from the VISTA (Virtual International Stroke Trials Archive), an international repository of clinical trials data. We reviewed relevant adverse events and classified patients into 2 cohorts based on the incidence of SHS. The SHS was defined as developing any cardiac complications within 30 days following stroke. Using Cox proportional hazards models, we evaluated the temporal risk dynamics of 90-day death associated with the day of SHS onset. We also compared the risk of 90-day death across SHS manifestations, using multivariate analysis. Among 15 054 patients with ischemic stroke (mean age, 69±12 years; 55% men), 1787 (11.8% [95% CI, 11.3-12.3]) developed SHS. The median onset time for SHS was 2 (interquartile range, 1-4) days. The most prevalent manifestation was other arrhythmia/ECG abnormalities, with the incidence rate of 6.5% (95% CI, 6.1-6.9). Patients who developed SHS between 10 and 30 days following stroke had significantly higher risks of death compared with those with SHS within the first 0 to 3 days (adjusted hazard ratio, 1.84 [95% CI, 1.36-2.49]). In the multivariate-adjusted analysis, SHS manifested as acute myocardial injury/myocardial injury, heart failure/left ventricular dysfunction, and atrial fibrillation/flutter were associated with the highest risk of death within 90 days after stroke across SHS manifestations excluding cardiorespiratory arrest. SHS is associated with a high risk of death, with a greater risk observed with delayed SHS onset.

Effect of ginkgo diterpene lactone meglumine on the quality of life in patients with acute ischemic stroke

ObjectiveGinkgo diterpene lactone meglumine (GDLM) could improve the functional outcome after acute ischemic stroke (AIS). This study aimed to investigate the efficacy of GDLM on the quality of life in patients with AIS in China.MethodsThis is a post hoc analysis of Efficacy and Safety of Ginkgo Diterpene Lactone Meglumine in Acute Ischemic Stroke trial. The quality of life was measured using the EuroQoL questionnaire, including EQ-5D and EQ visual analogue scale (EQ-VAS). The primary outcomes were changes in EQ-5D and EQ-VAS from baseline to day 14 and day 90 after randomization.ResultsA total of 3219 patients with completed data on outcomes were enrolled, with median age of 63 years (interquartile range, 55–70) and 2,067 (64.2%) men. GDLM was associated with a significant decrease in scores of ED-5Q components (from 0 [no problem] to 3[extreme problem]), the mean difference between GDLM and placebo group was -0.14 for mobility, -0.11 for usual activities and self-care, -0.09 for pain/discomfort, and -0.34 for anxiety/depression on day 14, respectively. Similar results were observed on day 90. Additionally, there was statistically significant difference of changes in EQ-VAS between the GDLM group and the placebo group from baseline to day 14 (mean difference, 1.70; 95% confidence interval [CI], 0.78–2.62; P = 0.0003) and to day 90 after randomization (mean difference, 3.29; 95% CI, 2.37–4.22; P < 0.001).ConclusionsIn this analysis of Chinese patients with AIS, GDLM could improve the 14-day and 90-day quality of life compared with the placebo.Trial registrationURL: https://www.clinicaltrials.gov. Unique identifier: NCT02526225. Registration Date: 2016–02-01.

Changing Landscape of Randomized Clinical Trials in Stroke: Explaining Contemporary Trial Designs and Methods.

Evidence generated from randomized clinical trials (RCTs) plays an indispensable role in advancing clinical stroke care. Although the number of stroke-related RCTs published every year has grown exponentially over the past 25 years, the execution and completion of RCTs, particularly those conducted in a hyperacute setting, have grown more complicated and challenging over the years. In addition to the practical challenges associated with conducting a clinical trial, like obtaining human subjects approval, identifying clinical sites, training trial personnel, and enrolling the target number of patients within the available funding and timeline, the complexity of contemporary RCT designs and analyses has become much more exacting. It is no longer sufficient to have a decent understanding of the 2-arm, placebo-controlled RCT, combined with a rudimentary grasp of the P value; things are now much more complicated. Innovations in trial design and analysis, including adaptive, Bayesian, platform, and noninferiority designs, have occurred to address the problems of poor trial efficiency. However, these advances require the end user to have a much greater level of understanding regarding the rationale, conduct, analysis, and interpretation of each design. While these newer designs seek greater efficiency, there are inevitably tradeoffs that need to be understood. In this month's edition of Stroke, we introduce a new series designed to help fill in these knowledge gaps. Over the next few months, 4 papers will be published that address major design innovations (adaptive, Bayesian, platform, and noninferiority) with the aim of illustrating how these approaches can make trials more efficient (where efficiency is defined as getting to the right answer, sooner, with a potentially lower sample size). In addition to introducing this series, this current article also reviews traditional hypothesis testing and the common misinterpretations of the P value; fortunately, new philosophical schools of inference are beginning to vanquish the overreliance on the P value. We are excited about the opportunity to educate the Stroke readership about these new trial designs and the profound implications that they bring.

Plasma Phenylacetylglutamine Levels and Prognosis of Ischemic Stroke: A Multicenter Prospective Study Based on the CATIS Trial.

Phenylacetylglutamine is implicated in platelet clotting and thrombosis, but its prognostic value in ischemic stroke remains unclear. We aimed to explore the associations of plasma phenylacetylglutamine levels with adverse outcomes after ischemic stroke in a multicenter prognostic cohort study. Our multicenter prognostic cohort study included 3564 Chinese patients with ischemic stroke from the CATIS (China Antihypertensive Trial in Acute Ischemic Stroke). All patients were followed up at 3 months after ischemic stroke onset. The primary outcome was the composite outcome of death or major disability (modified Rankin Scale score, 3-6) at 3 months after ischemic stroke. During 3 months of follow-up, 877 participants experienced the primary outcome. After multivariate adjustment, each 500 ng/mL increase of phenylacetylglutamine was associated with a 7% (P=0.012), 6% (P=0.016), and 6% (P=0.028) increased risk of the primary outcome, major disability, and death, respectively. The odds ratios or hazard ratios in the highest versus the lowest quartile of plasma phenylacetylglutamine were 1.62 ([95% CI, 1.18-2.23]; Ptrend=0.001) for the primary outcome, 1.62 ([95% CI, 1.16-2.24]; Ptrend=0.001) for major disability, and 2.59 ([95% CI, 1.19-5.60]; Ptrend=0.025) for death, respectively. There was a significantly worse shift in the distribution of modified Rankin Scale score at 3 months with higher phenylacetylglutamine quartiles (Ptrend=0.003). Multiple-adjusted spline regression model showed a linear relationship between phenylacetylglutamine and primary outcome (P value for linearity<0.001). The addition of plasma phenylacetylglutamine to conventional risk factors significantly improved the risk reclassification for the primary outcome (net reclassification improvement, 19.34%; P<0.001; integrated discrimination improvement, 0.23%; P=0.019). Elevated plasma phenylacetylglutamine levels at baseline were associated with increased risks of adverse clinical outcomes at 3 months after ischemic stroke, suggesting that phenylacetylglutamine may be a promising prognostic biomarker for ischemic stroke. Further studies are needed to investigate whether phenylacetylglutamine is a stroke-specific biomarker.

Improvements in Walking During Subacute Stroke Rehabilitation Translate to Physical Activity at the Chronic Stage: A Sub-Analysis From the Phys Stroke Trial.

ClinicalTrials.gov Identifier: NCT01953549.

An Introduction to Bayesian Approaches to Trial Design and Statistics for Stroke Researchers.

While the majority of stroke researchers use frequentist statistics to analyze and present their data, Bayesian statistics are becoming more and more prevalent in stroke research. As opposed to frequentist approaches, which are based on the probability that data equal specific values given underlying unknown parameters, Bayesian approaches are based on the probability that parameters equal specific values given observed data and prior beliefs. The Bayesian paradigm allows researchers to update their beliefs with observed data to provide probabilistic interpretations of key parameters, for example, the probability that a treatment is effective. In this review, we outline the basic concepts of Bayesian statistics as they apply to stroke trials, compare them to the frequentist approach using exemplary data from a randomized trial, and explain how a Bayesian analysis is conducted and interpreted.

POST‐UK (Adjunctive Intra‐Arterial Urokinase After Successful Endovascular Thrombectomy in Patients With Large‐Vessel Occlusion Stroke): Study Protocol of a Multicenter, Prospective, Randomized, Open‐Label, Blinded‐End Point Trial

BACKGROUND Intra‐arterial infusion of an adjunctive thrombolytic agent after macrovascular recanalization by endovascular thrombectomy was regarded as a promising strategy to promote outcomes of patients with stroke. Given the characteristics of urokinase as an affordable, available, and widely applied medication, especially in Eastern countries, this trial aims to assess the safety and efficacy of intra‐arterial urokinase as adjunct to endovascular thrombectomy in improving outcomes among patients with anterior large‐vessel occlusion stroke after excellent to complete reperfusion. METHODS The POST‐UK (Adjunctive Intra‐Arterial Urokinase After Successful Endovascular Thrombectomy in Patients With Large Vessel Occlusion Stroke) trial is a multicenter, prospective, randomized, open‐label, blinded‐end point trial conducted in China. The planned sample size is 498. Those eligible patients with anterior circulation large‐vessel occlusion stroke and achieving excellent to complete reperfusion by endovascular thrombectomy are planned to be consecutively randomized in a 1:1 ratio to the experimental group (a single dose of intra‐arterial urokinase) or to standard of care. RESULTS The primary outcome is a freedom from disability (modified Rankin Scale score of 0–1) at 90±7 days. The safety outcomes are mortality within 90±7 days and symptomatic intracranial hemorrhage within 48 hours. CONCLUSION The POST‐UK trial will provide valuable insight of efficacy and safety of intra‐arterial urokinase in patients with large‐vessel occlusion stroke after achieving excellent to complete reperfusion by endovascular thrombectomy.

Initial blood pressure and adverse cardiac events following acute ischaemic stroke: An individual patient data pooled analysis from the VISTA database.

Adverse cardiac events following ischaemic stroke (stroke-heart syndrome, SHS) pose a clinical challenge. We investigated the association between initial blood pressure at stroke presentation and the risk of SHS. We utilised data from the Virtual International Stroke Trials Archive (VISTA). We defined SHS as the incidence of cardiac complications within 30 days post-ischaemic stroke. These presentations included acute coronary syndrome encompassing myocardial injury, heart failure/left ventricular dysfunction, atrial fibrillation/flutter, other arrhythmia/electrocardiogram abnormalities, and cardiorespiratory arrest. Using Cox proportional hazards models, we assessed the risk trajectories for developing SHS and its presentations associated with initial blood pressure. We also explored the risk trajectories for 90-day mortality related to initial blood pressure. From 16,095 patients with acute ischaemic stroke, 14,965 (mean age 69 ± 12 years; 55% male) were analysed. Of these, 1774 (11.8%) developed SHS. The risk of SHS and initial blood pressure showed a U-shaped relationship. The lowest blood pressures (⩽130 mmHg systolic and ⩽55 mmHg diastolic) were associated with the highest risks (adjusted hazard ratio [95%confidence interval]: 1.40 [1.21-1.63]; p < 0.001, 1.71 [1.39-2.10]; p < 0.001, respectively, compared to referential blood pressure range).Cardiorespiratory arrest posed the greatest risk at higher blood pressure levels (2.34 [1.16-4.73]; p = 0.017 for systolic blood pressure >190 mmHg), whereas other presentations exhibited the highest risk at lower pressures. The 90-day mortality risk also followed a U-shaped distribution, with greater risks observed at high blood pressure thresholds. There is a U-shaped relationship between initial blood pressure at ischaemic stroke presentation and the risk of subsequent SHS.

Impact of selective reporting bias on stroke trials: potential compromise in evidence synthesis - A cross-sectional study

BackgroundAccurate reporting of outcomes is crucial for interpreting the results of randomized controlled trials (RCTs). However, selectively reporting outcomes in publications to achieve researchers’ anticipated results still occurs frequently. This study aims to investigate the prevalence of selective reporting of outcomes in RCTs on treating acute ischemic stroke (AIS), identify factors contributing to this issue, and assess its potential impact on the degree and direction of intervention effect.MethodsA search was conducted in MEDLINE, Embase, and the Cochrane Library to collect interventional RCTs on AIS published from 2020 to 2022. Full texts of RCTs were reviewed, and only those reporting International Clinical Trials Registry Platform primary registry numbers were included. Registration information of the RCTs was extracted from the registry platforms and compared with the publications’ details to assess the selective reporting of outcomes. Bayesian multilevel logistic regression was used to analyze the reasons behind selective reporting.ResultsAmong the total of 159 AIS RCTs identified, 82 (51.6%) were ultimately included, as they reported registration numbers, which encompassed 819 outcomes. Among them, 72 RCTs (87.8%) and 497 outcomes (60.7%) exhibited selective reporting. Omission-type selective reporting (downgrading, omitting, or ambiguously reporting) accounted for 36.4%, while addition-type selective reporting (upgrading, adding, or altering the measurement scope of outcomes) comprised 63.6%. Omission-type selective reporting correlated with negative results (OR: 7.39; 95% CI: 4.08—13.44), whereas addition-type selective reporting correlated with positive results (OR: 2.07; 95% CI: 1.34—3.26) and publication in journals that are not in the top quartile of the Journal Citation Reports (OR: 2.48; 95% CI: 1.15—5.38).ConclusionsRegistered interventional AIS RCTs still face significant issues regarding selective reporting of outcomes. Therefore, it is necessary to further evaluate the influence of selective reporting bias on the positive results obtained from individual AIS RCTs and the systematic reviews based on these RCTs.

The incidence and outcome of patients with early cardiovascular complications following intracerebral haemorrhage: An individual patient data pooled analysis from the VISTA database

Abstract Background Early cardiovascular (CV) complications in patients following intracerebral haemorrhage (ICH) is poorly understood. Such incident CV complications could be part of the so-called stroke-heart-syndrome occurring following ICH (SHS-ICH). We investigated the incidence and outcomes of patients with SHS-ICH. Methods Data were sought from the Virtual International Stroke Trials Archive (VISTA), an international repository of clinical trials data. We reviewed relevant adverse events and identified patients based on the incidence of cardiovascular complications within 30 days of post-ICH or ischaemic stroke (acute coronary syndrome [ACS] including acute myocardial injury, heart failure [HF]/left ventricular [LV] dysfunction, atrial fibrillation [AF]/atrial flutter [AFL], other arrhythmia/ ECG abnormalities, and cardio-respiratory arrest [CRA]). We conducted propensity score matching (PSM) to compare the incidence and outcomes of patients with SHS following ICH (SHS-ICH) with patients with SHS following acute ischaemic stroke (AIS). Poor outcome was defined as modified Rankin Scale, mRS ≥2, at 90 days. Results We pooled data from 12,438 participants recruited in acute stroke trials (mean age 68±12 years; 56% male), of which 1,171 (9.4%) were patients with ICH. Of the ICH patients, 150 patients (12.8%) had SHS-ICH. Following PSM, a total of 2,342 patients (1,171 for each of the ICH and AIS cohorts) were analysed. The incidence of SHS was not significantly different in the ICH and AIS cohorts (Table 1). The incidence of AF was significantly lower in patients with ICH compared to patients with AIS (1.5% vs. 4.5%, p&amp;lt;0.0001), despite comparable incidences of other arrhythmia/ECG abnormalities (9% vs. 9%, p=0.9). Multivariate-adjusted analysis found that SHS-ICH was associated with poor outcomes (Table 2, odds ratio, OR 1.08 [95%CI: 1.03-1.16], p=0.04, compared to ICH patients without SHS). Conclusions Stroke-heart syndrome is common and serves as a crucial prognostic marker in patient with ICH, with outcomes similar to SHS patients related to AIS. The development of SHS-ICH was associated with poorer outcomes compared to ICH patients without SHS.

Risk of death in patients with early cardiovascular complications following ischaemic stroke: an individual patient data pooled analysis from the VISTA database

Abstract Background Early cardiovascular complications may occur in patients following ischaemic stroke (stroke-heart-syndrome, SHS). We investigated the risk of death in patients with SHS, and across the SHS manifestations. Methods Data were sought from the Virtual International Stroke Trials Archive (VISTA), an international repository of clinical trials data. We reviewed relevant adverse events and classified patients into two cohorts based on the incidence of cardiovascular complications within 30 days post-stroke (acute coronary syndrome [ACS] including acute myocardial injury, heart failure [HF]/left ventricular [LV] dysfunction, atrial fibrillation [AF]/atrial flutter [AFL], other arrhythmia/ ECG abnormalities, and cardio-respiratory arrest [CRA]), i.e. those with SHS and those with stroke-only (without SHS). Using Cox proportional hazards model, we evaluated the 90-day risk of death trajectories associated with SHS. We also compared the 90-day risk of death across SHS manifestations excluding CRA, using multivariate analysis. Results Among 15,054 patients with ischaemic stroke (mean age 72±11 years; 55% male), 1,787 (11.8%; 95% confidence interval [CI]: 11.3-12.3, Table 1) developed SHS, with incidence peaked at day 3 post-stroke (interquartile range: 2-5). Other arrhythmia/ECG abnormalities were the most prevalent (6.5%; 95%CI: 6.1-6.9), followed by AF/AFL, HF/LV dysfunction, ACS/acute myocardial injury, and CRA. Patients who developed SHS between 10-30 days post-stroke had significantly higher risks of death compared to those with SHS within the first 0-3 days (adjusted hazard ratio [HR]: 2.13 [1.57-2.89]). In the multivariate-adjusted analysis which includes 13 background factors such as age and sex, SHS manifested as ACS/acute myocardial injury and HF/LV dysfunction were associated with highest risk of death within 90-day post-stroke (adjusted hazard ratio [HR] [95% CI], HR 2.13 (1.08-4.18) and HR 2.28 (1.42-3.66), respectively, Figure 1). Conclusions Stroke-heart syndrome is associated with high risk of death, with greater risk observed with the delayed SHS onset. Among the SHS manifestations, ACS/acute myocardial injury and HF/LV dysfunction were associated with the highest risk of death post-stroke.Figure 1

Typical profile of a patient with atrial fibrillation in the Russian population based on medical registries. A systematic review

Aim. To compare clinical and anamnestic characteristics of patients with atrial fibrillation (AF) included in three large international stu­dies assessing the efficacy and safety of therapy with direct oral anti­coagu­lants, with the profile of a typical Russian patient with AF in clinical practi­ce, established by medical registries in the Russian Federation (RF).Material and methods. A systematic review of scientific publications was con­ducted. The search was conducted in the E-library and Google Scholar databases. Publications from 8 registries of patients with AF, con­ducted in the Russian Federation from 2012 to 2023, were found, which present the clinical and anamnestic characteristics of patients. All studies included in the analysis meet the generally accepted require­ments for medical registries. The systematic review protocol was pre­viously recorded in the PROSPERO electronic database (CRD42024512425).Results. A Russian patient with AF is a patient with a large number of cardiovascular pathologies and a high risk of thromboembolic events. According to the analysis, Russian patient with AF has an average age of ~70 years. Most patients have a diagnosis of hypertension, heart failure, while from one third to half of patients have a diagnosis of chronic kidney disease. From 20 to 30% of patients have a history of myocardial infarction and every fifth patient has type 2 diabetes.Conclusion. In all countries around the world, including the Russian Fe­deration, for many years, medical registries have been one of the main sources of information on the characteristics of patients with AF and the disease course. They can supplement the available data from randomized clinical trials with real-world data. Comparison of clinical and anamnestic characteristics of patients in randomized clinical trials of direct oral anticoagulants with characteristics of patients in the Russian registries shows that patients included in the Rivaroxaban Once Daily Oral Direct Factor Xa Inhibition Compared with Vitamin K An­tagonism for Prevention of Stroke and Embolism Trial in Atrial Fib­rillation (ROCKET AF trial) were most similar to Russian patients with AF.

Adaptive Trials in Stroke: Current Use and Future Directions.

Inclusion of adaptive design features in a clinical trial provides preplanned flexibility to dynamically modify a trial during its conduct while preserving validity and integrity. Adaptive trials are needed to accelerate the conduct of more efficient, informative, and ethical clinical research in the field of neurology. Stroke is a natural candidate for adoption of these innovative approaches to trial design. This Research Methods in Neurology article is informed by a scoping review that identified 45 completed or ongoing adaptive clinical trials in stroke that were appraised: 15 trials had published results with or without a published protocol and 30 ongoing trials (14 trials had a published protocol, and 16 trials were registered only). Interventions spanned acute (n = 28), rehabilitation (n = 8), prevention (n = 8), and rehabilitation and prevention (n = 1). A subsample of these trials was selected to illustrate the utility of adaptive design features and discuss why each adaptive feature was incorporated in the design to best achieve the aim; whether each individual feature was used and whether it resulted in expected efficiencies; and any learnings during preparation, conduct, or reporting. We then discuss the operational, ethical, and regulatory considerations that warrant careful consideration during adaptive trial planning and reflect on the workforce readiness to deliver adaptive trials in practice. We conclude that adaptive trials can be designed, funded, conducted, and published for a wide range of research questions and offer future directions to support adoption of adaptive trial designs in stroke and neurologic research more broadly.

Adaptive Clinical Trials in Stroke.

Designing a clinical trial to evaluate the efficacy of an intervention is often complicated by uncertainty over aspects of the study population, potential treatment effects, most relevant outcomes, dropouts, and other factors. However, once participants begin to be enrolled and partial trial data become available, this level of uncertainty is reduced. Adaptive clinical trials are designed to take advantage of the accumulating data during the conduct of a trial to make changes according to prespecified decision rules to increase the likelihood of success or statistical efficiency. Common adaptive rules address early stopping for benefit or futility, sample size reestimation, adding or dropping treatment arms or altering randomization ratios, and changing the eligibility criteria to focus on responder patient subgroups. Adaptive clinical trials are gaining popularity for clinical stroke research. We provide an overview of the methods, practical considerations, challenges and limitations, and potential future role of adaptive clinical trials in advancing knowledge and practice in stroke.

Advance Consent for Participation in Acute Stroke Trials: A Focus Group Study with People with Lived Experience of Stroke.

Advance consent could address many of the limitations traditional consenting methods pose to participation in acute stroke trials. We conducted a series of five focus groups with people with lived experience of stroke. Using an inductive thematic approach, two themes were developed: factors in favour of, and against, advance consent. Participants supported the idea of advance consent and highlighted trust, transparent communication and sufficient time as major factors that would positively affect their decision to provide advance consent. The results will be used to finalise a model of advance consent suitable for testing the feasibility in stroke prevention clinics.