Prediction of early recurrent thromboembolic event and major bleeding in patients with acute stroke and atrial fibrillation by a risk stratification schema: the ALESSA score study

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

The risk of stroke recurrence in patients with atrial fibrillation and reduced ejection fraction

Abstract Background: Atrial fibrillation (AF) and congestive heart failure often coexist due to their shared risk factors leading to potential worse outcome, particularly cerebrovascular events. The aims of this study were to calculate the rates of ischemic and severe bleeding events in ischemic stroke patients having both AF and reduced ejection fraction (rEF) (⩽40%), compared to ischemic stroke patients with AF but without rEF. Methods: We performed a retrospective analysis that drew data from prospective studies. The primary outcome was the composite of either ischemic (stroke or systemic embolism), or hemorrhagic events (symptomatic intracranial bleeding and severe extracranial bleeding). Results: The cohort for this analysis comprised 3477 patients with ischemic stroke and AF, of which, 643 (18.3%) had also rEF. After a mean follow-up of 7.5 ± 9.1 months, 375 (10.8%) patients had 382 recorded outcome events, for an annual rate of 18.0%. While the number of primary outcome events in patients with rEF was 86 (13.4%), compared to 289 (10.2%) for the patients without rEF; on multivariable analysis rEF was not associated with the primary outcome (OR 1.25; 95% CI 0.84–1.88). At the end of follow-up, 321 (49.9%) patients with rEF were deceased or disabled (mRS ⩾3), compared with 1145 (40.4%) of those without rEF; on multivariable analysis, rEF was correlated with mortality or disability (OR 1.35; 95% CI 1.03–1.77). Conclusions: In patients with ischemic stroke and AF, the presence of rEF was not associated with the composite outcome of ischemic or hemorrhagic events over short-term follow-up but was associated with increased mortality or disability

Anticoagulation After Stroke in Patients With Atrial Fibrillation : To Bridge or Not With Low-Molecular-Weight Heparin?

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 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.Peer reviewe

Ανίχνευση παροξυσμικής Κολπικής Μαρμαρυγής σε ασθενείς με κρυπτογενή ισχαιμικά αγγειακά εγκεφαλικά επεισόδια

Το ισχαιμικο εγκεφαλικό επεισόδιο(ΙΑΕΕ) είναι η πιο συχνή υποομάδα των ΑΕΕ που εμφανίζεται σε όλες τις ηλικιακές ομάδες και ο καθορισμός του αιτιοπαθολογικού μηχανισμού καθορίζει σε σημαντικό βαθμό την αντιμετώπιση, την έκβαση και την δευτερογενή πρόληψη στους ασθενείς αυτούς. Σε ένα ποσοστό 30-40% των ΙΑΕΕ παρά τον εκτεταμένο διαγνωστικό έλεγχο δεν βρίσκεται ο μηχανισμός και τα έμφρακτα αυτά ονομάζονται κρυπτογενή. Τα τελευταία χρόνια τα κρυπτογενή ΙΑΕΕ έχουν γίνει αντικείμενο μελέτης ιδιαιτέρα προς την κατεύθυνση ανίχνευσης κολπικής μαρμαρυγής (ΚΜ) ως υποκείμενο αιτιοπαθολογικό μηχανισμό. Η αρρυθμία αυτή που συχνά είναι παροξυσμική και ασυμπτωματική, επιφέρει υψηλό κίνδυνο θρομβοεμβολής με την αντιπηκτική αγωγή να υπερτερεί της αντιαιμοπεταλιακής στην πρόληψη ΙΑΕΕ και συστημικών εμβολών.Σκοπός της μελέτης αυτής ήταν να διερευνήσουμε την συχνότητα εμφάνισης παροξυσμικής κολπικής μαρμαρυγής (ΠΚΜ) σε ασθενείς με κΙΑΕΕ με τον κλασσικό καρδιολογικό έλεγχο και με επαναλαμβανόμενα 24ωρα Holter ρυθμού, να μελετήσουμε την πιθανή συσχέτιση νευρουπερηχογραφικών ή και νευροαπεικονιστικών ευρημάτων με την συχνότητα ανίχνευσης ΠΚΜ, καθώς επίσης να εξετάσουμε την πιθανή συσχέτιση της διάρκειας της ΠΚΜ με την νευρολογική βαρύτητα του ΙΑΕΕIschemic stroke (IAE) is the most common subgroup of stroke occurring in all age groups. The determination of the etiopathological mechanism dictates the treatment, the prognosis and the secondary prevention in these patients. Often the causes are undetermined (cryptogenic ischemc stroke) despite the extensive diagnostc evaluation. The last years, many trials were conducted in order to determine the best method to detect atrial firbillation in patients withn cryptogenic stroke. Atrial fibrillation (AF) is an known frequently asymptomatic and paroxysmal arrtythmia with high thromboembolic risk. The detection of AF is important in the clinical practice because anticoagulation therapy benefits compared to antiplatetels, on the secondary prevention of stroke and systemic thromboembolism.The purpose of our study was to investigate the incidence of paroxysmal atrial fibrillation in patients with cryptogenic stroke with common cardiac assessment and with repeated 24-hour Holter- ECG's , to study the possible contribution of neurovascular imaging and neuroimaging to the detection rate of AF and finally to examine the possible correlation of the duration of paroxysmal atrial firbillation and the severity of the ischemic strok

Detection of paroxysmal atrial fibrillation in patients with cryptogenic ischemic stroke

Ischemic stroke (IAE) is the most common subgroup of stroke occurring in all age groups. The determination of the etiopathological mechanism dictates the treatment, the prognosis and the secondary prevention in these patients. Often the causes are undetermined (cryptogenic ischemc stroke) despite the extensive diagnostc evaluation. The last years, many trials were conducted in order to determine the best method to detect atrial firbillation in patients withn cryptogenic stroke. Atrial fibrillation (AF) is an known frequently asymptomatic and paroxysmal arrtythmia with high thromboembolic risk. The detection of AF is important in the clinical practice because anticoagulation therapy benefits compared to antiplatetels, on the secondary prevention of stroke and systemic thromboembolism.The purpose of our study was to investigate the incidence of paroxysmal atrial fibrillation in patients with cryptogenic stroke with common cardiac assessment and with repeated 24-hour Holter- ECG's, to study the possible contribution of neurovascular imaging and neuroimaging to the detection rate of AF and finally to examine the possible correlation of the duration of paroxysmal atrial firbillation and the severity of the ischemic stroke.Το ισχαιμικο εγκεφαλικό επεισόδιο(ΙΑΕΕ) είναι η πιο συχνή υποομάδα των ΑΕΕ που εμφανίζεται σε όλες τις ηλικιακές ομάδες και ο καθορισμός του αιτιοπαθολογικού μηχανισμού καθορίζει σε σημαντικό βαθμό την αντιμετώπιση, την έκβαση και την δευτερογενή πρόληψη στους ασθενείς αυτούς. Σε ένα ποσοστό 30-40% των ΙΑΕΕ παρά τον εκτεταμένο διαγνωστικό έλεγχο δεν βρίσκεται ο μηχανισμός και τα έμφρακτα αυτά ονομάζονται κρυπτογενή. Τα τελευταία χρόνια τα κρυπτογενή ΙΑΕΕ έχουν γίνει αντικείμενο μελέτης ιδιαιτέρα προς την κατεύθυνση ανίχνευσης κολπικής μαρμαρυγής (ΚΜ) ως υποκείμενο αιτιοπαθολογικό μηχανισμό. Η αρρυθμία αυτή που συχνά είναι παροξυσμική και ασυμπτωματική, επιφέρει υψηλό κίνδυνο θρομβοεμβολής με την αντιπηκτική αγωγή να υπερτερεί της αντιαιμοπεταλιακής στην πρόληψη ΙΑΕΕ και συστημικών εμβολών. Σκοπός της μελέτης αυτής ήταν να διερευνήσουμε την συχνότητα εμφάνισης παροξυσμικής κολπικής μαρμαρυγής (ΠΚΜ) σε ασθενείς με κΙΑΕΕ με τον κλασσικό καρδιολογικό έλεγχο και με επαναλαμβανόμενα 24ωρα Holter ρυθμού, να μελετήσουμε την πιθανή συσχέτιση νευρουπερηχογραφικών ή και νευροαπεικονιστικών ευρημάτων με την συχνότητα ανίχνευσης ΠΚΜ, καθώς επίσης να εξετάσουμε την πιθανή συσχέτιση της διάρκειας της ΠΚΜ με την νευρολογική βαρύτητα του ΙΑΕΕ

Early Recurrence and Major Bleeding in Patients With Acute Ischemic Stroke and Atrial Fibrillation Treated With Non-Vitamin-K Oral Anticoagulants (RAF-NOACs) Study

Background-The 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 theirtiming in patients with acute ischemic stroke and atrial fibrillation who received NOACs for secondary prevention. Methods and Results-Recurrence 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. Conclusions-In 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.Peer reviewe

Early recurrence in paroxysmal versus sustained atrial fibrillation in patients with acute ischaemic stroke

Background The relationship between different patterns of atrial fibrillation and early recurrence after an acute ischaemic stroke is unclear. Purpose In a prospective cohort study, we evaluated the rates of early ischaemic recurrence after an acute ischaemic stroke in patients with paroxysmal atrial fibrillation or sustained atrial fibrillation which included persistent and permanent atrial fibrillation. Methods In patients with acute ischaemic stroke, atrial fibrillation was categorised as paroxysmal atrial fibrillation or sustained atrial fibrillation. Ischaemic recurrences were the composite of ischaemic stroke, transient ischaemic attack and symptomatic systemic embolism occurring within 90 days from acute index stroke. Results A total of 2150 patients (1155 females, 53.7%) were enrolled: 930 (43.3%) had paroxysmal atrial fibrillation and 1220 (56.7%) sustained atrial fibrillation. During the 90-day follow-up, 111 ischaemic recurrences were observed in 107 patients: 31 in patients with paroxysmal atrial fibrillation (3.3%) and 76 with sustained atrial fibrillation (6.2%) (hazard ratio (HR) 1.86 (95% CI 1.24-2.81)). Patients with sustained atrial fibrillation were on average older, more likely to have diabetes mellitus, hypertension, history of stroke/ transient ischaemic attack, congestive heart failure, atrial enlargement, high baseline NIHSS-score and implanted pacemaker. After adjustment by Cox proportional hazard model, sustained atrial fibrillation was not associated with early ischaemic recurrences (adjusted HR 1.23 (95% CI 0.74-2.04)). Conclusions After acute ischaemic stroke, patients with sustained atrial fibrillation had a higher rate of early ischaemic recurrence than patients with paroxysmal atrial fibrillation. After adjustment for relevant risk factors, sustained atrial fibrillation was not associated with a significantly higher risk of recurrence, thus suggesting that the risk profile associated with atrial fibrillation, rather than its pattern, is determinant for recurrence.Peer reviewe

Causes and Risk Factors of Cerebral Ischemic Events in Patients With Atrial Fibrillation Treated With Non–Vitamin K Antagonist Oral Anticoagulants for Stroke Prevention : the RENo study

Background and Purpose- Despite treatment with oral anticoagulants, patients with nonvalvular atrial fibrillation (AF) may experience ischemic cerebrovascular events. The aims of this case-control study in patients with AF were to identify the pathogenesis of and the risk factors for cerebrovascular ischemic events occurring during non-vitamin K antagonist oral anticoagulants (NOACs) therapy for stroke prevention. Methods- Cases were consecutive patients with AF who had acute cerebrovascular ischemic events during NOAC treatment. Controls were consecutive patients with AF who did not have cerebrovascular events during NOACs treatment. Results- Overall, 713 cases (641 ischemic strokes and 72 transient ischemic attacks; median age, 80.0 years; interquartile range, 12; median National Institutes of Health Stroke Scale on admission, 6.0; interquartile range, 10) and 700 controls (median age, 72.0 years; interquartile range, 8) were included in the study. Recurrent stroke was classified as cardioembolic in 455 cases (63.9%) according to the A-S-C-O-D (A, atherosclerosis; S, small vessel disease; C, cardiac pathology; O, other causes; D, dissection) classification. On multivariable analysis, off-label low dose of NOACs (odds ratio [OR], 3.18; 95% CI, 1.95-5.85), atrial enlargement (OR, 6.64; 95% CI, 4.63-9.52), hyperlipidemia (OR, 2.40; 95% CI, 1.83-3.16), and CHA <sub>2</sub> DS <sub>2</sub> -VASc score (OR, 1.72 for each point increase; 95% CI, 1.58-1.88) were associated with ischemic events. Among the CHA <sub>2</sub> DS <sub>2</sub> -VASc components, age was older and presence of diabetes mellitus, congestive heart failure, and history of stroke or transient ischemic attack more common in patients who had acute cerebrovascular ischemic events. Paroxysmal AF was inversely associated with ischemic events (OR, 0.45; 95% CI, 0.33-0.61). Conclusions- In patients with AF treated with NOACs who had a cerebrovascular event, mostly but not exclusively of cardioembolic pathogenesis, off-label low dose, atrial enlargement, hyperlipidemia, and high CHA <sub>2</sub> DS <sub>2</sub> -VASc score were associated with increased risk of cerebrovascular events

Risk of recurrent stroke in patients with atrial fibrillation treated with oral anticoagulants alone or in combination with anti-platelet therapy

Introduction: Ischaemic stroke patients with atrial fibrillation (AF) are at high risk of stroke recurrence despite oral anticoagulation therapy. Patients with cardiovascular comorbidities may take both antiplatelet and oral anticoagulation therapy (OAC/AP). Our study aims to evaluate the safety and efficacy of OAC/AP therapy as secondary prevention in people with AF and ischaemic stroke. Patients and methods: We performed a post-hoc analysis of pooled individual data from multicenter prospective cohort studies and compared outcomes in the OAC/AP cohort and patients on DOAC/VKA anticoagulation alone (OAC cohort). Primary outcome was a composite of ischaemic stroke, systemic embolism, intracranial bleeding, and major extracranial bleeding, while secondary outcomes were ischaemic and haemorrhagic events considered separately. A multivariable logistic regression analysis was performed to identify independent predictors for outcome events. To compare the risk of outcome events between the two cohorts, the relation between the survival function and the set of explanatory variables were calculated by Cox proportional hazard models and the results were reported as adjusted hazard ratios (HR). Finally another analysis was performed to compare the overall risk of outcome events in both OAC/AP and OAC cohorts after propensity score matching (PSM). Results: During a mean follow-up time of 7.5 ± 9.1 months (median follow-up time 3.5 months, interquartile range ±3), 2284 stroke patients were on oral anticoagulants and 215 were on combined therapy. The multivariable model demonstrated that the composite outcome is associated with age (OR: 1.03, 95% CI: 1.01-1.04 for each year increase) and concomitant antiplatelet therapy (OR: 2.2, 95% CI: 1.48-3.27), the ischaemic outcome with congestive heart failure (OR: 1.55, 95% CI: 1.02-2.36) and concomitant antiplatelet therapy (OR: 1.93, 95% CI: 1.19-3.13) and the haemorrhagic outcome with age (OR: 1.03, 95% CI: 1.01-1.06 for each year increase), alcoholism (OR: 2.15, 95% CI: 1.06-4.39) and concomitant antiplatelet therapy (OR: 2.22, 95% CI: 1.23-4.02). Cox regression demonstrated a higher rate of the composite outcome (hazard ratio of 1.93 [95% CI, 1.35-2.76]), ischaemic events (HR: 2.05 [95% CI: 1.45-2.87]) and bleeding outcomes (HR: 1.90 [95% CI, 1.06-3.40]) in OAC/AP cohort. After PSM analysis, the composite outcome remained more frequent in people treated with OAC + AP (RR: 1.70 [95% CI, 1.05-2.74]). Discussion: Secondary prevention with combination of oral anticoagulant and antiplatelet therapy after ischaemic stroke was associated with worse outcomes in our cohort. Conclusion: Further research is needed to improve secondary prevention by investigating the mechanisms of recurrent ischaemic stroke in patients with atrial fibrillation