Background and Purpose— The best time for administering anticoagulation therapy in acute cardioembolic stroke remains unclear. This prospective cohort study of patients with acute stroke and atrial fibrillation, evaluated (1) the risk of recurrent ischemic event and severe bleeding; (2) the risk factors for recurrence and bleeding; and (3) the risks of recurrence and bleeding associated with anticoagulant therapy and its starting time after the acute stroke. Methods— The primary outcome of this multicenter study was the composite of stroke, transient ischemic attack, symptomatic systemic embolism, symptomatic cerebral bleeding and major extracranial bleeding within 90 days from acute stroke. Results— Of the 1029 patients enrolled, 123 had 128 events (12.6%): 77 (7.6%) ischemic stroke or transient ischemic attack or systemic embolism, 37 (3.6%) symptomatic cerebral bleeding, and 14 (1.4%) major extracranial bleeding. At 90 days, 50% of the patients were either deceased or disabled (modified Rankin score ≥3), and 10.9% were deceased. High CHA 2 DS 2 -VASc score, high National Institutes of Health Stroke Scale, large ischemic lesion and type of anticoagulant were predictive factors for primary study outcome. At adjusted Cox regression analysis, initiating anticoagulants 4 to 14 days from stroke onset was associated with a significant reduction in primary study outcome, compared with initiating treatment before 4 or after 14 days: hazard ratio 0.53 (95% confidence interval 0.30–0.93). About 7% of the patients treated with oral anticoagulants alone had an outcome event compared with 16.8% and 12.3% of the patients treated with low molecular weight heparins alone or followed by oral anticoagulants, respectively ( P =0.003). Conclusions— Acute stroke in atrial fibrillation patients is associated with high rates of ischemic recurrence and major bleeding at 90 days. This study has observed that high CHA 2 DS 2 -VASc score, high National Institutes of Health Stroke Scale, large ischemic lesions, and type of anticoagulant administered each independently led to a greater risk of recurrence and bleedings. Also, data showed that the best time for initiating anticoagulation treatment for secondary stroke prevention is 4 to 14 days from stroke onset. Moreover, patients treated with oral anticoagulants alone had better outcomes compared with patients treated with low molecular weight heparins alone or before oral anticoagulants.

Background and purpose Recent observations linked coronavirus disease 2019 (COVID‐19) to thromboembolic complications possibly mediated by increased blood coagulability and inflammatory endothelial impairment. We aimed to define the risk of acute stroke in patients with severe and non‐severe COVID‐19. Methods We performed an observational, multicenter cohort study in four participating hospitals in Saxony, Germany to characterize consecutive patients with laboratory‐confirmed COVID‐19 who experienced acute stroke during hospitalization. Furthermore, we conducted a systematic review using PubMed/MEDLINE, Embase, Cochrane Library and bibliographies of identified papers following Preferred Reporting Items for Systematic Reviews and Meta‐Analyses guidelines including data from observational studies of acute stroke in COVID‐19 patients. Data were extracted by two independent reviewers and pooled with multicenter data to calculate risk ratios (RRs) and 95% confidence intervals (95% CIs) for acute stroke related to COVID‐19 severity using a random‐effects model. Between‐study heterogeneity was assessed using Cochran’s Q and I2 statistics. International Prospective Register of Systematic Reviews registration number: CRD42020187194. Results Of 165 patients hospitalized for COVID‐19 (49.1% males, median age = 67 years [57–79 years], 72.1% severe or critical) included in the multicenter study, overall stroke rate was 4.2% (95% CI: 1.9–8.7). Systematic literature search identified two observational studies involving 576 patients that were eligible for meta‐analysis. Amongst 741 pooled COVID‐19 patients, overall stroke rate was 2.9% (95% CI: 1.9–4.5). Risk of acute stroke was increased for patients with severe compared to non‐severe COVID‐19 (RR = 4.18, 95% CI: 1.7–10.25; P = 0.002) with no evidence of heterogeneity (I2 = 0%, P = 0.82). Conclusions Synthesized analysis of data from our multicenter study and previously published cohorts indicates that severity of COVID‐19 is associated with an increased risk of acute stroke.

Background In patients with acute ischemic stroke and atrial fibrillation, early anticoagulation prevents ischemic recurrence but with the risk of hemorrhagic transformation ( HT ). The aims of this study were to evaluate in consecutive patients with acute stroke and atrial fibrillation (1) the incidence of early HT, (2) the time to initiation of anticoagulation in patients with HT , (3) the association of HT with ischemic recurrences, and (4) the association of HT with clinical outcome at 90 days. Methods and Results HT was diagnosed by a second brain computed tomographic scan performed 24 to 72 hours after stroke onset. The incidence of ischemic recurrences as well as mortality or disability (modified Rankin Scale scores >2) were evaluated at 90 days. Ischemic recurrences were the composite of ischemic stroke, transient ischemic attack, or systemic embolism. Among the 2183 patients included in the study, 241 (11.0%) had HT . Patients with and without HT initiated anticoagulant therapy after a mean 23.3 and 11.6 days, respectively, from index stroke. At 90 days, 4.6% (95% confidence interval, 2.3–8.0) of the patients with HT had ischemic recurrences compared with 4.9% (95% confidence interval, 4.0–6.0) of those without HT ; 53.1% of patients with HT were deceased or disabled compared with 35.8% of those without HT . On multivariable analysis, HT was associated with mortality or disability (odds ratio, 1.71; 95% confidence interval, 1.24–2.35). Conclusions In patients with HT , anticoagulation was initiated about 12 days later than patients without HT . This delay was not associated with increased detection of ischemic recurrence. HT was associated with increased mortality or disability.

required in patients who received intravenous thrombolysis prior to transfer in a drip-and-ship approach (29 of 35 [82.9%] patients vs. 192 of 308 [62.3%] patients; p = 0.016; Table 4). In contrast, only one (6.3%) of the non-intubated patients with BAO required medication during transfer. Patients who required medical interventions during the transfer had a higher systolic blood pressure, a higher heart rate and a lower oxygen saturation on departure. The need for transfer-related medical interventions was Number, n 377

Paciaroni, M. et al. (2016) Prognostic value of trans-thoracic echocardiography in patients with acute stroke and atrial fibrillation: findings from the RAF study. Journal of Neurology, 263(2), pp. 231-237. (doi:10.1007/s00415-015-7957-3) There may be differences between this version and the published version. You are advised to consult the publisher's version if you wish to cite from it.http://eprints.gla.ac.uk/117439/ UO Gravi Cerebrolesioni, San Giovanni Battista Hospital, Foligno. These authors take responsibility for all aspects of the reliability and freedom from bias of the data presented and their discussed interpretation. 23 Stroke Unit, Department of Neurology, Sant'Andrea Hospital, La Spezia, Italy. These authors take responsibility for all aspects of the reliability and freedom from bias of the data presented and their discussed interpretation. 24 Department of Internal Medicine, Insubria University, Varese, Italy. These authors take responsibility for all aspects of the reliability and freedom from bias of the data presented and their discussed interpretation. 25 Stroke Unit, Neurology, Insubria University, Varese, Italy. These authors take responsibility for all aspects of the reliability and freedom from bias of the data presented and their discussed interpretation. 26 Stroke Unit, Ospedale di Portogruaro, Portogruaro (Venice), Italy. These authors take responsibility for all aspects of the reliability and freedom from bias of the data presented and their discussed interpretation. 27 Department of Neurology, University of L'Aquila, Italy. These authors take responsibility for all aspects of the reliability and freedom from bias of the data presented and their discussed interpretation. 28 Department of Internal Medicine, Ospedale Civile di Piacenza, Italy. These authors take responsibility for all aspects of the reliability and freedom from bias of the data presented and their discussed interpretation. 29 Municipal Budgetary Healthcare Institution of Novosibirsk. City Clinical Hospital #1. Novosibirsk (Russia) 30 Stroke Unit, Jazzolino Hospital, Vibo Valentia, Italy. These authors take responsibility for all aspects of the reliability and freedom from bias of the data presented and their discussed interpretation. 31 Department of Neurology and Psychiatry, Sapienza University of Rome, Italy. These authors take responsibility for all aspects of the reliability and freedom from bias of the data presented and their discussed interpretation. 32 Stroke Unit, Ospedale Civico, Palermo. These authors take responsibility for all aspects of the reliability and freedom from bias of the data presented and their discussed interpretation. The Authors report that no funding has been received for this study. 4Abstract Background and purposes: Anticoagulant therapy is recommended for the secondary

Background Coma is associated with poor outcome in patients with basilar artery occlusion. Aims We sought to assess whether the posterior circulation Acute Stroke Prognosis Early CT Score and the Pons-Midbrain Index applied to CT angiography source images predict the outcome of comatose patients in the Basilar Artery International Cooperation Study. Methods Basilar Artery International Cooperation Study was a prospective, observational registry of patients with acute basilar artery occlusion with 48 recruiting centers worldwide. We applied posterior circulation Acute Stroke Prognosis Early CT Score and Pons-Midbrain Index to CT angiography source images of Basilar Artery International Cooperation Study patients who presented with coma. We calculated adjusted risk ratios to assess the association of dichotomized posterior circulation Acute Stroke Prognosis Early CT Score (≥8 vs. <8) and Pons-Midbrain Index (<3 vs. ≥3) with mortality and favourable outcome (modified Rankin Scale score 0-3) at one month. Results Of 619 patients in the Basilar Artery International Cooperation Study registry, CT angiography source images were available for review in 158 patients. Among these, 78 patients (49%) presented with coma. Compared to non-comatose patients, comatose patients were more likely to die (risk ratios 2.34; CI 95% 1.56-3.52) and less likely to have a favourable outcome (risk ratios 0.44; CI 95% 0.24-0.80). Among comatose patients, a Pons-Midbrain Index < 3 was related to reduced mortality (adjusted RR 0.66; 95% CI 0.46-0.96), but not to favourable outcome (adjusted RR 1.19; 95% CI 0.39-3.62). Posterior circulation Acute Stroke Prognosis Early CT Score dichotomized at ≥ 8 vs. <8 was not significantly associated with death (adjusted RR 0.70; 95% CI 0.46-1.05). Conclusion In comatose patients with basilar artery occlusion, the extent of brainstem ischemia appears to be related to mortality but not to favourable outcome.

Background and Purpose-Bridging therapy with low-molecular-weight heparin reportedly leads to a worse outcome for acute cardioembolic stroke patients because of a higher incidence of intracerebral bleeding. However, this practice is common in clinical settings. This observational study aimed to compare (1) the clinical profiles of patients receiving and not receiving bridging therapy, (2) overall group outcomes, and (3) outcomes according to the type of anticoagulant prescribed. Methods-We analyzed data of patients from the prospective RAF and RAF-NOACs studies. The primary outcome was defined as the composite of ischemic stroke, transient ischemic attack, systemic embolism, symptomatic cerebral bleeding, and major extracerebral bleeding observed at 90 days after the acute stroke. Results-Of 1810 patients who initiated oral anticoagulant therapy, 371 (20%) underwent bridging therapy with full-dose low-molecular-weight heparin. Older age and the presence of leukoaraiosis were inversely correlated with the use of bridging therapy. Forty-two bridged patients (11.3%) reached the combined outcome versus 72 (5.0%) of the nonbridged patients (P=0.0001). At multivariable analysis, bridging therapy was associated with the composite end point (odds ratio, 2.3; 95% CI, 1.4-3.7; P<0.0001), as well as ischemic (odds ratio, 2.2; 95% CI, 1.3-3.9; P=0.005) and hemorrhagic (odds ratio, 2.4; 95% CI, 1.2-4.9; P=0.01) end points separately. Conclusions-Our findings suggest that patients receiving low-molecular-weight heparin have a higher risk of early ischemic recurrence and hemorrhagic transformation compared with nonbridged patients.

Background and Purposes— This study was designed to derive and validate a score to predict early ischemic events and major bleedings after an acute ischemic stroke in patients with atrial fibrillation. Methods— The derivation cohort consisted of 854 patients with acute ischemic stroke and atrial fibrillation included in prospective series between January 2012 and March 2014. Older age (hazard ratio 1.06 for each additional year; 95% confidence interval, 1.00–1.11) and severe atrial enlargement (hazard ratio, 2.05; 95% confidence interval, 1.08–2.87) were predictors for ischemic outcome events (stroke, transient ischemic attack, and systemic embolism) at 90 days from acute stroke. Small lesions (≤1.5 cm) were inversely correlated with both major bleeding (hazard ratio, 0.39; P =0.03) and ischemic outcome events (hazard ratio, 0.55; 95% confidence interval, 0.30–1.00). We assigned to age ≥80 years 2 points and between 70 and 79 years 1 point; ischemic index lesion >1.5 cm, 1 point; severe atrial enlargement, 1 point (ALESSA score). A logistic regression with the receiver-operating characteristic graph procedure (C statistic) showed an area under the curve of 0.697 (0.632–0.763; P =0.0001) for ischemic outcome events and 0.585 (0.493–0.678; P =0.10) for major bleedings. Results— The validation cohort consisted of 994 patients included in prospective series between April 2014 and June 2016. Logistic regression with the receiver-operating characteristic graph procedure showed an area under the curve of 0.646 (0.529–0.763; P =0.009) for ischemic outcome events and 0.407 (0.275–0.540; P =0.14) for hemorrhagic outcome events. Conclusions— In acute stroke patients with atrial fibrillation, high ALESSA scores were associated with a high risk of ischemic events but not of major bleedings.