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Introduction The risk of hemorrhagic transformation (HT) in the early phase of acute ischemic stroke (AIS) remains unknown, leading to potential unnecessary delays in initiation of anticoagulation for secondary stroke prevention. We sought to assess the rate of HT associated withdirect oral anticoagulant (DOAC) initiation within and beyond 48 hours after AIS, using a pooled analysis of available published data. Methods A pooled analysis of 6 studies (4 prospective observational blinded outcome studies and2 randomized trials) of DOAC initiation within 14 days of AIS or transient ischemic attack (TIA) was conducted. The primary endpoint was incident radiographic HT on follow‐up imaging. Secondary endpoints included symptomatic HT, new parenchymal hemorrhage, recurrent ischemic events, extracranial hemorrhage, mortality within the study period, and follow‐up modified Rankin Scale score.The results were reported as odds ratio (OR) andhazard ratio (HR)with 95% confidence interval (CI). Results We evaluated 509 patients; median infarct volume was1.5 (0.1‐7.8) ml, andmedian National Institutes of Health Stroke Scale was2 (0‐3).Incident radiographic HT was seen on follow‐up scan in 34 (6.8%) patients.DOAC initiation within 48 hours from index event was not associated with incident HT (adjusted OR 0.67, [0.30 – 1.50]P = 0.32).No patients developed symptomatic HT.Conversely, 31 (6.1%) patients developedrecurrent ischemic events, 64% of which occurred within 14 days.Initiating a DOAC within 48 hours of onset was associated with a trend towards lower rates of recurrent ischemic events, but this was not statistically significant (HR 0.42, [0.17 – 1.008]P = 0.052). In contrast to HT,recurrent ischemic events were associated with poor functional outcomes (OR = 6.8, [2.84 – 16.24], p< 0.001). Conclusions Initiation of DOAC within 48 hours after stroke was not associated with decreased risk of recurrent ischemic events, or increasedincident risk of HT. Both recurrent ischemic events and incident HT occurred at similar rates.Unlike HT, however, recurrent ischemic events were associated with poor outcomes.

Background In light of evidence from recent trials that endovascular thrombectomy (EVT) alone may potentially be noninferior to combined treatment, that is, with intravenous thrombolysis (IVT) with alteplase and EVT, we sought to understand physician and patient preferences around this issue. Methods We conducted a 2‐stage mixed methods study that included a structured, international, web‐based cross‐sectional survey among stroke physicians, and a focus group involving stroke survivors and caregivers. Demographic information was collected from all participants. The survey offered multiple choice questions and options to respond via free text which was analyzed quantitatively. The focus group was conducted online and analyzed qualitatively using a grounded theory approach. Results A total of 225 physicians (67% men) from 44 countries completed the survey. Most participants (70%) were between 31 and 50 years of age. Survey results showed that in current practice, 90% respondents would offer IVT to patients with large vessel occlusion stroke eligible for both IVT and EVT. When asked if their practice would change in light of recent trials, 63% responded no. When asked about the appropriate timing for IVT in the setting of large vessel occlusion stroke with EVT availability, 56% preferred to administer IVT immediately, 21% were willing to defer the decision for 30 minutes from groin puncture, and 8% were willing to defer for 60 minutes from groin puncture to assess if reperfusion was achieved with EVT. A total of 61% participants would choose to use tenecteplase over alteplase as the preferred drug for IVT if both drugs are backed by evidence. The focus group identified a need to better understand patient characteristics that may benefit from EVT‐only or combined strategies. The focus group also identified the need for more data to inform physician decision making. Conclusions Most physicians surveyed prefer IVT before EVT in patients with acute ischemic stroke attributable to large vessel occlusion, although there was some uncertainty around this issue. The need for further studies, including data on IVT with tenecteplase and among various patient subgroups to inform decision making, was apparent from both the survey and the patient focus group.

Introduction: The timing of direct oral anticoagulant (DOAC) after atrial fibrillation (AF)-related stroke is unknown. Most guidelines are inconsistent and based on expert opinion. We conducted a survey to evaluate the global practice patterns of this common clinical scenario. Methods: We used an electronic survey with practice-related demographic and clinical questions of 10 cases with different stroke severities and sizes: transient ischemic attack, small, medium, large, and strokes with hemorrhagic infarction and parenchymal hematoma. Results: A total of 242 clinicians from 21 countries completed at least one clinical scenario. The majority of the respondents were from Australia (36.4%) or Canada (22.7%). Stroke-specific sub-specialty training was self-reported in 82.2% of the respondents. Median (IQR) time spent dedicated to stroke patient care/research was 70 (60) % of total working hours. Only 14% of responding clinicians reported current participation in a randomized trial of DOAC initiation timing after AF-related stroke. Stroke size, severity, and the grade of hemorrhage if present seem to be determinants of the decisions. Lack of consensus was observed in moderate stroke, multi-territory infarcts, large stroke, and in the presence of HT. The majority of respondents would be willing to randomize patients with different stroke sizes and severities with/without HT in a clinical trial of early versus delayed initiation of DOAC after AF-related stroke. Conclusions: Decisions related to the timing of DOAC initiation after AF-related stroke vary globally. The variability in clinical practice will continue until randomized controlled trials are completed.

Background: Atrial fibrillation (AF) is a common cause of ischemic stroke; however, it is often difficult to detect. It is unclear whether specific infarct topography on magnetic resonance imaging (MRI) is associated with underlying AF. We aimed to objectively assess the infarct patterns on MRI in patients with acute ischemic stroke and determine imaging characteristics that are associated with AF. Methods: We conducted a subgroup analysis on patients randomized in Post-Embolic Rhythm Detection with Implantable vs External Monitoring trial (PER DIEM; NCT02428140) who had brain MRI. Two raters blinded to clinical details reviewed the MRI findings. Patients were divided to two groups (AF and non-AF) and descriptive statistics were used to characterize findings. Variables associated with new AF were analyzed using logistic regression and reported as odds ratios (OR) with 95% confidence interval (CI) and p -values. Results: Of the 300 patients who were randomized in the trial, 249 (83%) patients (59.4% male) with a mean age of 64.3 ± 13.1 years had MRI brain and were included in the analysis. Median (IQR) NIHSS was 0 (0 - 1), number of lesions was 2 (1 - 3), and diameter of lesion (mm) was 10.4 (5.8 - 21.1) mm. In this cohort of patients, imaging characteristics were not significantly associated with the detection of AF. Conclusions: Association between infarct topography and AF detection was not found in this study. Imaging characteristics cannot be relied upon to predict or exclude an underlying AF. Large prospective studies are suggested to examine the link between infarct topography and underlying AF.

Introduction: Early anticoagulation after acute ischemic stroke is usually avoided due to the risk of hemorrhagic transformation (HT). We aimed to assess the rate of radiological HT associated with direct oral anticoagulant (DOAC) initiation within 48 hours vs. > 48 hours in the post-stroke period. Methods: A pooled analysis of five studies of DOAC initiation within 14 days of ischemic stroke onset was conducted. The primary endpoint was incident radiographic HT on follow-up imaging. Secondary endpoints included symptomatic HT, new parenchymal hemorrhage (PH1 or asymptomatic PH2), recurrent systemic events, systemic hemorrhagic complications, mortality within the study period, final modified Rankin Scale score. The results were reported as odds ratio (OR) with 95% confidence interval (CI). Results: A total of 468 patients were enrolled. Median infarct volume was 1.35 (0-7.5) ml, and National Institutes of Health Stroke Scale was 1 (0-3). Incident radiographic HT was seen on follow-up scan in 29 patients. DOAC initiation within 48 hours from index event onset was not associated with incident HT (adjusted OR 0.67, [0.31 - 1.50] P =0.34). No patients developed symptomatic HT. Conversely, 25 patients developed recurrent ischemic events, 64% of which occurred within 14 days. Initiating DOAC within 48 hours of onset was not associated with a reduction in the risk of recurrent ischemic events (OR 0.47, [0.19 - 1.20] P =0.12). In contrast to HT, recurrent ischemic events were associated with poor functional outcomes (OR=6.8, [2.95 - 15.63], p Conclusions: Early DOAC initiation after stroke was not associated with increased incident HT risk. Recurrent ischemic events were common and associated with poor outcomes. These data may be useful for estimating outcome rates and sample size calculations in future trials of early versus late DOAC initiation after AF-related stroke.

Background: The optimal timing of anticoagulation after stroke in patients with atrial fibrillation (AF) is unknown. Patients and methods: A prospective, open label study (NCT04435418) of patients with AF treated with apixaban within 14 days of ischemic stroke/TIA onset was conducted. Baseline and follow-up CT scans were assessed for hemorrhagic transformation (HT) and graded using European Cooperative Acute Stroke Study (ECASS) criteria. The primary endpoint was symptomatic HT. Incident HT rates were assessed as Objective Performance Criteria. Results: One-hundred AF stroke patients, with a mean age of 79±11 years were enrolled. Median infarct volume was 4 (0.5-10.75) ml. Median time from index event onset to apixaban initiation was 2 (1-6) days, and median baseline NIHSS was 4 (1-9). Asymptomatic HT on baseline imaging was present in 15 patients. Infarct volume (OR= 1.1, [1.02-1.12], P Discussion: Early apixaban treatment did not precipitate symptomatic HT after stroke. All HT was asymptomatic identified on imaging. Recurrent ischemic events were common and clinically symptomatic. Conclusions: Symptomatic HT rates are likely to be low in randomized trials of DOAC initiation post-stroke. Recurrent ischemic stroke may be the major clinical outcome.