BackgroundThe optimal timing to administer non–vitamin K oral anticoagulants (NOACs) in patients with acute ischemic stroke and atrial fibrillation is unclear. This prospective observational multicenter study evaluated the rates of early recurrence and major bleeding (within 90 days) and their timing in patients with acute ischemic stroke and atrial fibrillation who received NOACs for secondary prevention.Methods and ResultsRecurrence was defined as the composite of ischemic stroke, transient ischemic attack, and symptomatic systemic embolism, and major bleeding was defined as symptomatic cerebral and major extracranial bleeding. For the analysis, 1127 patients were eligible: 381 (33.8%) were treated with dabigatran, 366 (32.5%) with rivaroxaban, and 380 (33.7%) with apixaban. Patients who received dabigatran were younger and had lower admission National Institutes of Health Stroke Scale score and less commonly had a CHA 2 DS 2‐VASc score >4 and less reduced renal function. Thirty‐two patients (2.8%) had early recurrence, and 27 (2.4%) had major bleeding. The rates of early recurrence and major bleeding were, respectively, 1.8% and 0.5% in patients receiving dabigatran, 1.6% and 2.5% in those receiving rivaroxaban, and 4.0% and 2.9% in those receiving apixaban. Patients who initiated NOACs within 2 days after acute stroke had a composite rate of recurrence and major bleeding of 12.4%; composite rates were 2.1% for those who initiated NOACs between 3 and 14 days and 9.1% for those who initiated >14 days after acute stroke.ConclusionsIn patients with acute ischemic stroke and atrial fibrillation, treatment with NOACs was associated with a combined 5% rate of ischemic embolic recurrence and severe bleeding within 90 days.

Background and Purpose: There is interest in what happens over time to the thrombus after intravenous alteplase. We study the effect of alteplase on thrombus structure and its impact on clinical outcome in patients with acute stroke. Methods: Intravenous alteplase treated stroke patients with intracranial internal carotid artery or middle cerebral artery occlusion identified on baseline computed tomography angiography and with follow-up vascular imaging (computed tomography angiography or first run of angiography before endovascular therapy) were enrolled from INTERRSeCT study (Identifying New Approaches to Optimize Thrombus Characterization for Predicting Early Recanalization and Reperfusion With IV Alteplase and Other Treatments Using Serial CT Angiography). Thrombus movement after intravenous alteplase was classified into complete recanalization, thrombus migration, thrombus fragmentation, and no change. Thrombus migration was diagnosed when occlusion site moved distally and graded according to degrees of thrombus movement (grade 0–3). Thrombus fragmentation was diagnosed when a new distal occlusion in addition to the primary occlusion was identified on follow-up imaging. The association between thrombus movement and clinical outcome was also evaluated. Results: Among 427 patients in this study, thrombus movement was seen in 54% with a median time of 123 minutes from alteplase administration to follow-up imaging, and sub-classified as marked (thrombus migration grade 2–3 + complete recanalization; 27%) and mild to moderate thrombus movement (thrombus fragmentation + thrombus migration grade 0–1; 27%). In patients with proximal M1/internal carotid artery occlusion, marked thrombus movement was associated with a higher rate of good outcome (90-day modified Rankin Scale, 0–2) compared with mild to moderate movement (52% versus 27%; adjusted odds ratio, 5.64 [95% CI, 1.72–20.10]). No difference was seen in outcomes between mild to moderate thrombus movement and no change. In M1 distal/M2 occlusion, marked thrombus movement was associated with improved 90-day good outcome compared with no change (70% versus 56%; adjusted odds ratio, 2.54 [95% CI, 1.21–5.51]). Conclusions: Early thrombus movement is common after intravenous alteplase. Marked thrombus migration leads to good clinical outcomes. Thrombus dynamics over time should be further evaluated in clinical trials of acute reperfusion therapy.

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.

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.