Anticoagulation Type and Early Recurrence in Cardioembolic Stroke

Background and Purpose: In patients with acute ischemic stroke and atrial fibrillation, treatment with low molecular weight heparin increases early hemorrhagic risk without reducing early recurrence, and there is limited data comparing warfarin to direct oral anticoagulant (DOAC) therapy. We aim to compare the effects of the treatments above on the risk of 90-day recurrent ischemic events and delayed symptomatic intracranial hemorrhage. Methods: We included consecutive patients with acute ischemic stroke and atrial fibrillation from the IAC (Initiation of Anticoagulation after Cardioembolic) stroke study pooling data from stroke registries of 8 comprehensive stroke centers across the United States. We compared recurrent ischemic events and delayed symptomatic intracranial hemorrhage between each of the following groups in separate Cox-regression analyses: (1) DOAC versus warfarin and (2) bridging with heparin/low molecular weight heparin versus no bridging, adjusting for pertinent confounders to test these associations. Results: We identified 1289 patients who met the bridging versus no bridging analysis inclusion criteria and 1251 patients who met the DOAC versus warfarin analysis inclusion criteria. In adjusted Cox-regression models, bridging (versus no bridging) treatment was associated with a high risk of delayed symptomatic intracranial hemorrhage (hazard ratio, 2.74 [95% CI, 1.01–7.42]) but a similar rate of recurrent ischemic events (hazard ratio, 1.23 [95% CI, 0.63–2.40]). Furthermore, DOAC (versus warfarin) treatment was associated with a lower risk of recurrent ischemic events (hazard ratio, 0.51 [95% CI, 0.29–0.87]) but not delayed symptomatic intracranial hemorrhage (hazard ratio, 0.57 [95% CI, 0.22–1.48]). Conclusions: Our study suggests that patients with ischemic stroke and atrial fibrillation would benefit from the initiation of a DOAC without bridging therapy. Due to our study limitations, these findings should be interpreted with caution pending confirmation from large prospective studies.

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Characteristics of ischemic stroke and intracranial hemorrhage in patients with nephrotic syndrome

BMC Nephrology ◽

10.1186/s12882-021-02415-w ◽

2021 ◽

Vol 22 (1) ◽

Author(s):

Wen-Yi Huang ◽

Chun-Wei Chang ◽

Chiung-Mei Chen ◽

Kuan-Hsing Chen ◽

Chien-Hung Chang ◽

...

Keyword(s):

Nephrotic Syndrome ◽

Ischemic Stroke ◽

Intracranial Hemorrhage ◽

Cox Regression ◽

Hazard Ratio ◽

Chang Gung Memorial Hospital ◽

Cerebral Stroke ◽

Research Database ◽

Anterior Circulation ◽

Cox Regression Analysis

Abstract Background The incidence of cerebral stroke, including ischemic infarction and intracranial hemorrhage (ICH), increases in patients with nephrotic syndrome (NS). However, the clinical characteristics of patients with NS and stroke remain elusive. We aimed to investigate the clinical presentation and prognosis among patients with NS and ischemic stroke (IS) or ICH. Methods We conducted a population-based retrospective cohort study of patients with NS and acute stroke using the Chang Gung Research Database of Taiwan from January 1, 2001, to December 31, 2017. The participants were recruited from the 7 branches of Chang Gung Memorial Hospital. Results A total of 233 patients with IS and 57 patients with ICH were enrolled. The median age was 60 (52–70) years. The prevalence rates of hyperlipidemia, hyperuricemia, and smoking were higher in IS than in ICH. IS demonstrated lower white blood cell count (7.80 vs. 8.92 × 109/L) and high-sensitivity C-reactive protein level (33.42 vs. 144.10 nmol/L) and higher cholesterol (5.74 vs. 4.84 mmol/L), triglyceride (1.60 vs. 1.28 mmol/L), and albumin (24 vs. 18 g/L) levels compared with ICH. The dependent functional status and 30-day mortality were higher in ICH than in IS. The risk factors for 30-day mortality for patients with NS and stroke were coronary artery disease (CAD), ICH, and total anterior circulation syndrome. The multivariate Cox regression analysis revealed that CAD was positively associated with 30-day mortality in patients with IS (hazard ratio 24.58, 95 % CI 1.48 to 408.90). In patients with ICH, CAD and subarachnoid hemorrhage were positively associated with 30-day mortality (hazard ratio 5.49, 95 % CI 1.54 to 19.56; hazard ratio 6.32, 95 % CI 1.57 to 25.53, respectively). Conclusions ICH demonstrated a higher risk of dependence and 30-day mortality compared with IS in patients with NS. Intensive monitoring and treatment should be applied particularly in patients with NS and ICH.

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Association of Preceding Antithrombotic Therapy in Atrial Fibrillation Patients With Ischemic Stroke, Intracranial Hemorrhage, or Gastrointestinal Bleed and Mortality

European Heart Journal - Cardiovascular Pharmacotherapy ◽

10.1093/ehjcvp/pvz063 ◽

2019 ◽

Cited By ~ 3

Author(s):

Joris J Komen ◽

Tomas Forslund ◽

Aukje K Mantel-Teeuwisse ◽

Olaf H Klungel ◽

Mia von Euler ◽

...

Keyword(s):

Atrial Fibrillation ◽

Ischemic Stroke ◽

Propensity Score ◽

Intracranial Hemorrhage ◽

Cox Regression ◽

Mortality Rates ◽

Antithrombotic Treatment ◽

Healthcare Database ◽

Gastrointestinal Bleed ◽

History Of

Abstract Aims To analyze 90-day mortality in AF patients after a stroke or a severe bleed and assess associations with the type of antithrombotic treatment at the event. Methods and Results From the Stockholm Healthcare database, we selected 6 017 patients with a known history of AF who were diagnosed with ischemic stroke, 3 006 with intracranial hemorrhage, and 4 291 with a severe gastrointestinal bleed (GIB). The 90-day mortality rates were 25.1% after ischemic stroke, 31.6% after intracranial hemorrhage, and 16.2% after severe GIB. We used Cox regression and propensity score matched analyses to test the association between antithrombotic treatment at the event and 90-day mortality. After intracranial hemorrhage, there was a significantly higher mortality rate in warfarin compared to NOAC treated patients (adjusted hazard ratio (aHR): 1.36 CI: 1.04 – 1.78). After an ischemic stroke and a severe GIB, patients receiving antiplatelets or no antithrombotic treatment had significantly higher mortality rates compared to patients on NOACs, but there was no difference comparing warfarin to NOACs (aHR 0.84 CI: 0.63 – 1.12 after ischemic stroke, aHR 0.91 CI: 0.66 – 1.25 after severe GIB). Propensity score matched analysis yielded similar results. Conclusion Mortality rates were high in AF patients suffering from an ischemic stroke, an intracranial hemorrhage, or a severe GIB. NOAC treatment was associated with a lower 90 day mortality after intracranial hemorrhage than warfarin.

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MRI predicts intracranial hemorrhage in patients who receive long-term oral anticoagulation

Neurology ◽

10.1212/wnl.0000000000007532 ◽

2019 ◽

Vol 92 (21) ◽

pp. e2432-e2443 ◽

Cited By ~ 18

Author(s):

Joan Martí-Fàbregas ◽

Santiago Medrano-Martorell ◽

Elisa Merino ◽

Luis Prats-Sánchez ◽

Rebeca Marín ◽

...

Keyword(s):

Ischemic Stroke ◽

White Matter ◽

Intracranial Hemorrhage ◽

White Matter Hyperintensities ◽

Cox Regression ◽

Multivariable Analysis ◽

Hazard Ratio ◽

Superficial Siderosis ◽

Increased Risk

ObjectiveWe tested the hypothesis that the risk of intracranial hemorrhage (ICH) in patients with cardioembolic ischemic stroke who are treated with oral anticoagulants (OAs) can be predicted by evaluating surrogate markers of hemorrhagic-prone cerebral angiopathies using a baseline MRI.MethodsPatients were participants in a multicenter and prospective observational study. They were older than 64 years, had a recent cardioembolic ischemic stroke, and were new users of OAs. They underwent a baseline MRI analysis to evaluate microbleeds, white matter hyperintensities, and cortical superficial siderosis. We collected demographic variables, clinical characteristics, risk scores, and therapeutic data. The primary endpoint was ICH that occurred during follow-up. We performed bivariate and multivariate Cox regression analyses.ResultsWe recruited 937 patients (aged 77.6 ± 6.5 years; 47.9% were men). Microbleeds were detected in 207 patients (22.5%), moderate/severe white matter hyperintensities in 419 (45.1%), and superficial siderosis in 28 patients (3%). After a mean follow-up of 23.1 ± 6.8 months, 18 patients (1.9%) experienced an ICH. In multivariable analysis, microbleeds (hazard ratio 2.7, 95% confidence interval [CI] 1.1–7, p = 0.034) and moderate/severe white matter hyperintensities (hazard ratio 5.7, 95% CI 1.6–20, p = 0.006) were associated with ICH (C index 0.76, 95% CI 0.66–0.85). Rate of ICH was highest in patients with both microbleed and moderate/severe WMH (3.76 per 100 patient-years, 95% CI 1.62–7.4).ConclusionPatients taking OAs who have advanced cerebral small vessel disease, evidenced by microbleeds and moderate to severe white matter hyperintensities, had an increased risk of ICH. Our results should help to determine the risk of prescribing OA for a patient with cardioembolic stroke.ClinicalTrials.gov identifierNCT02238470.

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Abstract P532: Does Atrial Fibrillation Impact Rate of Symptomatic Intracranial Hemorrhage in Acute Ischemic Stroke Patients Treated With rt-PA and/or Endovascular Treatment?

Stroke ◽

10.1161/str.52.suppl_1.p532 ◽

2021 ◽

Vol 52 (Suppl_1) ◽

Author(s):

Reza Bavarsad Shahripour ◽

Benjamin Shifflett ◽

Edward Labin ◽

Morgan Figurelle ◽

Anna Barminova ◽

...

Keyword(s):

Atrial Fibrillation ◽

Ischemic Stroke ◽

Endovascular Treatment ◽

Acute Ischemic Stroke ◽

Intracranial Hemorrhage ◽

Smoking Status ◽

Intravenous Thrombolysis ◽

Significant Difference ◽

Chi Squared ◽

Symptomatic Intracranial Hemorrhage

Background: Patients with acute ischemic stroke (AIS) due to atrial fibrillation (afib) may have increased complications from intravenous thrombolysis or endovascular treatment (ET) compared to other stroke subtypes. The purpose of this study was to compare the rates of symptomatic intracranial hemorrhage (sICH) in patients with and without a history of a fib treated with IV rt-PA and/or ET. Methods: Consecutive stroke code activations were retrospectively analyzed from January 2004-June 2020 at an academic comprehensive stroke center. Patients were included if they were treated with IV rt-PA and/or ET within 24 hours of stroke onset. Patients were stratified into the six groups:1-No hx of a fib with ET only, 2-Hx of a fib with ET only, 3-No hx of a fib with IV rt-PA plus ET, 4-Hx of a fib with IV rt-PA plus ET, 5-No hx of a fib with IV rt-PA only, 6-Hx of a fib with IV rt-PA only. Primary outcome was defined as any sICH within 72 hours of treatment using the NINDS definition. Baseline demographics were compared. Chi squared was used to assess differences in sICH rates and logistic regression to compare individual groups. Analyses were both unadjusted and adjusted for baseline NIHSS, age, sex, baseline blood pressure, pre-stroke mRS, smoking status, and baseline glucose. Results: We identified 720 AIS patients who received acute treatment (IV rt-PA: n=578; ET: n=100; IV rt-PA+ET:n=18). There was a significant difference in sex (p=0.005); Hispanic ethnicity (p=0.002); current smoking (p=<0.001); current alcohol use (p=0.03), CHF (p=0.01); and age (p<0.0001) between groups. Baseline NIHSS was significantly higher in Group 4 (23, SD 8, p=<0.001).In adjusted analysis, there was no significant difference in sICH in patients with a fib after receiving IVtPA (OR 1.53, CI 0.47-4.99, p=0.48), ET (OR 0.93 , CI 0-∞, p=1.00), or both (OR 0.25,CI 0.00-9.07, p=0.45) compared to those without afib. There was no significant difference in sICH in adjusted analyses in patients with and without a fib overall (OR 0.93, CI 0-∞, p=1.00). Conclusion: In this study, atrial fibrillation did not have a significant impact on rates of sICH in AIS patients treated with IV rt-PA, ET, or both. This study supports the safety of IV rt-PA, ET, and combination therapy in the atrial fibrillation population.

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Abstract 63: Three-month Outcomes in Japanese Stroke /TIA Patients With Non-valvular Atrial Fibrillation After Initiating Oral Anticoagulants: The SAMURAI-NVAF Study

Stroke ◽

10.1161/str.46.suppl_1.63 ◽

2015 ◽

Vol 46 (suppl_1) ◽

Author(s):

Shoji Arihiro ◽

Kenichi Todo ◽

Masatoshi Koga ◽

Hiroshi Yamagami ◽

Tadashi Terasaki ◽

...

Keyword(s):

Atrial Fibrillation ◽

Ischemic Stroke ◽

Intracranial Hemorrhage ◽

Recurrent Stroke ◽

Oral Anticoagulants ◽

Bleeding Events ◽

Nonvalvular Atrial Fibrillation ◽

Fatal Bleeding ◽

Index Stroke ◽

Ischemic Events

Backgound and Purpose: Recently, three non-vitamin K antagonist oral anticoagulants (NOACs) became available for patients with nonvalvular atrial fibrillation (NVAF) in Japan. We aimed to determine 3-month outcomes in ischemic stroke/TIA patients receiving NOACs or warfarin from a multicenter prospective registry (SAMURAI-NVAF registry, NCT01581502). Methods: Among 1,191 acute ischemic stroke /TIA patients enrolled between September 2011 and March 2014, we studied 916 patients (389 women, 77±10 y) who took oral anticoagulants (OACs) after index stroke and completed 3-month follow-up survey. Primary outcome measures were ischemic events, including recurrent stroke/TIA and thromboembolism, and major bleedings events, such as fatal bleeding and/or symptomatic bleeding in a critical area or organ according to the International Society on Thrombosis and Haemostasis statement. We assessed the incidence and clinical factors associated with primary outcomes within 90 days after initiating OACs. Results: NOACs were given for 370 patients (126 women, 74±9 y; dabigatran 168, rivaroxaban 183 and apixaban 19) and warfarin for 546 (263 women, 79±10 y). NOAC users had lower scores of CHADS2 (median 3 in NOAC, 4 in warfarin, p<0.001) and HAS-BLED (3, 3, p<0.001) than warfarin users. Ischemic events occurred in 14 NOAC users (3.8%; 2 women, 76±6 y, including 8 lower dose users between two approved dose for each NOAC) and 25 warfarin users (4.6%; 13 women, 81±9 y). Of these, 13 NOAC users (3.5%) and 16 warfarin users (2.9%) developed ischemic stroke/TIA. Among NOAC users, patients with ischemic events had lower body weights (53±11 vs 60±11kg, p= 0.017), more frequently had congestive heart failure (36 vs 10%, p = 0.003) and intracardiac thrombus (27 vs 4%, p < 0.001) than those without. Major bleeding events occurred in 5 NOAC users (1.4%, all using lower dose), and 14 warfarin users (2.6%). Of these, one NOAC user (0.3%) and 4 warfarin users (0.7%) developed intracranial hemorrhage. Conclusion: The 3-month incidence of ischemic events in stroke/TIA patients with NVAF was approximately 4% in both NOAC and warfarin users. Intracranial hemorrhage was relatively infrequent in NOAC users.

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3053High mortality in atrial fibrillation patients suffering ischemic stroke, intracranial hemorrhage or a gastrointestinal bleed and associations with the preceding antithrombotic treatment

European Heart Journal ◽

10.1093/eurheartj/ehz745.0020 ◽

2019 ◽

Vol 40 (Supplement_1) ◽

Author(s):

J J Komen ◽

T Forslund ◽

A K Mantel - Teeuwisse ◽

O H Klungel ◽

B Wettermark ◽

...

Keyword(s):

Atrial Fibrillation ◽

Ischemic Stroke ◽

Propensity Score ◽

Intracranial Hemorrhage ◽

Cox Regression ◽

Mortality Rates ◽

Antithrombotic Treatment ◽

Gastrointestinal Bleed ◽

Increased Risk ◽

Significant Difference

Abstract Background Anticoagulation treatment reduces the risk of stroke but increases the risk of bleeding in atrial fibrillation (AF) patients. There is little data on survival after a stroke or a severe bleed. Objective To analyze 90-day mortality in AF patients after an ischemic stroke, an intracranial hemorrhage (ICH) or a gastrointestinal bleed (GIB) and assess associations with the type of antithrombotic treatment preceding the event. Methods From the Stockholm Healthcare database (n=2.3 million inhabitants) we selected all AF patients suffering from an ischemic stroke, an intracranial bleed, or a severe GIB requiring acute hospital care between July 2011 and August 2018 and assessed 90-day mortality rates. We assessed current use of warfarin, non-vitamin K oral anticoagulants (NOAC), or antiplatelet agents at the time of the event. We used a Cox regression to calculate adjusted hazard ratios (aHRs), adjusting for components of the Charlson Comorbidity Index, the CHADsVASc score, the HAS-BLED score, comedication, and year of inclusion, for the association between treatment preceding the event and mortality. In addition, we performed log-rank tests in propensity score matched cohorts. Results Of 105 313 patients with AF, 6 017 were included after an ischemic stroke, 3 006 after an ICH, and 4 291 after a GIB. 90-day mortality rates were 25.1%, 31.6% and 16.2%, respectively. Patients suffering from an ischemic stroke were the oldest at 81.6±9.8 (S.D:) years of age followed by patients suffering from an ICH (80.2±9.8 years) or a GIB (78.7±10.5 years). A large proportion of patients suffering ischemic stroke (72%) had no anticoagulant treatment preceding the event. After ICH, there was a significantly increased risk of mortality in warfarin compared to NOAC treated patients after adjusting for confounders (aHR: 1.36 CI: 1.04–1.78). Patients receiving antiplatelets or no treatment had significantly higher mortality rates than patients on NOAC treatment, both after an ischemic stroke and a GIB, but there was no significant difference between warfarin and NOACs (aHR 0.84 CI: 0.63–1.12 after ischemic stroke, aHR 0.91 CI: 0.66–1.25 after GIB). Propensity score matched analyses yielded similar results. Survival curves after event Conclusion Mortality rates are high in AF patients suffering from an ischemic stroke, an ICH, or a GIB. NOAC treatment was associated with a lower 90-day mortality after ICH than warfarin, but no such difference was found after ischemic stroke or GIB. After ischemic stroke and GIB, mortality rates were higher in antiplatelet treated and untreated patients compared to NOAC treated patients. Acknowledgement/Funding Swedish Heart Lung Foundation

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Tenecteplase Thrombolysis for Acute Ischemic Stroke

Stroke ◽

10.1161/strokeaha.120.029749 ◽

2020 ◽

Vol 51 (11) ◽

pp. 3440-3451

Author(s):

Steven J. Warach ◽

Adrienne N. Dula ◽

Truman J. Milling

Keyword(s):

Ischemic Stroke ◽

Intracranial Hemorrhage ◽

Time Window ◽

Large Vessel ◽

Bolus Administration ◽

Phase 2 ◽

Qualitative Synthesis ◽

Phase 3 ◽

Symptomatic Intracranial Hemorrhage ◽

Meta Analyses

Tenecteplase is a fibrinolytic drug with higher fibrin specificity and longer half-life than the standard stroke thrombolytic, alteplase, permitting the convenience of single bolus administration. Tenecteplase, at 0.5 mg/kg, has regulatory approval to treat ST-segment–elevation myocardial infarction, for which it has equivalent 30-day mortality and fewer systemic hemorrhages. Investigated as a thrombolytic for ischemic stroke over the past 15 years, tenecteplase is currently being studied in several phase 3 trials. Based on a systematic literature search, we provide a qualitative synthesis of published stroke clinical trials of tenecteplase that (1) performed randomized comparisons with alteplase, (2) compared different doses of tenecteplase, or (3) provided unique quantitative meta-analyses. Four phase 2 and one phase 3 study performed randomized comparisons with alteplase. These and other phase 2 studies compared different tenecteplase doses and effects on early outcomes of recanalization, reperfusion, and substantial neurological improvement, as well as symptomatic intracranial hemorrhage and 3-month disability on the modified Rankin Scale. Although no single trial prospectively demonstrated superiority or noninferiority of tenecteplase on clinical outcome, meta-analyses of these trials (1585 patients randomized) point to tenecteplase superiority in recanalization of large vessel occlusions and noninferiority in disability-free 3-month outcome, without increases in symptomatic intracranial hemorrhage or mortality. Doses of 0.25 and 0.4 mg/kg have been tested, but no advantage of the higher dose has been suggested by the results. Current clinical practice guidelines for stroke include intravenous tenecteplase at either dose as a second-tier option, with the 0.25 mg/kg dose recommended for large vessel occlusions, based on a phase 2 trial that demonstrated superior recanalization and improved 3-month outcome relative to alteplase. Ongoing randomized phase 3 trials may better define the comparative risks and benefits of tenecteplase and alteplase for stroke thrombolysis and answer questions of tenecteplase efficacy in the >4.5-hour time window, in wake-up stroke, and in combination with endovascular thrombectomy.

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P-003 Association between baseline serology and symptomatic intracranial hemorrhage after endovascular thrombectomy for acute ischemic stroke

10.1136/neurintsurg-2021-snis.39 ◽

2021 ◽

Author(s):

J Diestro ◽

C Parra-Farinas ◽

M Balas ◽

Z Zador ◽

N Almusalam ◽

...

Keyword(s):

Ischemic Stroke ◽

Acute Ischemic Stroke ◽

Intracranial Hemorrhage ◽

Endovascular Thrombectomy ◽

Symptomatic Intracranial Hemorrhage

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Safety of early anticoagulation in patients treated with urgent reperfusion for acute ischemic stroke related to non-valvular atrial fibrillation

European Heart Journal ◽

10.1093/ehjci/ehaa946.2431 ◽

2020 ◽

Vol 41 (Supplement_2) ◽

Author(s):

M Giustozzi

Keyword(s):

Atrial Fibrillation ◽

Ischemic Stroke ◽

Acute Ischemic Stroke ◽

Major Bleeding ◽

Oral Anticoagulation ◽

Primary Outcome ◽

Oral Anticoagulants ◽

Early Recurrence ◽

Optimal Timing ◽

Hemorrhagic Event

Abstract Background The optimal timing for starting anticoagulation after an acute ischemic stroke related to non-valvular atrial fibrillation (AF) remains a challenge, especially in patients treated with systemic thrombolysis or mechanical thrombectomy. Purpose We aimed to assess the rates of early recurrence and major bleeding in patients with acute ischemic stroke and AF treated with thrombolytic therapy and/or thrombectomy who received oral anticoagulants for secondary prevention. Methods We combined the dataset of the RAF and the RAF-NOACs studies, which were prospective observational studies carried out from January 2012 to March 2014 and April 2014 to June 2016, respectively. We included consecutive patients with acute ischemic stroke and AF treated with either vitamin K antagonists (VKAs) or new oral anticoagulants (NOACs). Primary outcome was the composite of stroke, transient ischemic attack, symptomatic systemic embolism, symptomatic cerebral bleeding, and major extracerebral bleeding within 90 days from the inclusion. Results A total of 2,159 patients were included in the RAF and RAF-NOACs trials, of which 564 patients (26%) were treated with urgent reperfusion therapy. After acute stroke, 505 (90%) patients treated with reperfusion and 1,287 out of the 1,595 (81%) patients not treated with reperfusion started oral anticoagulation. Timing of starting oral anticoagulation was similar in reperfusion-treated and untreated patients (13.5±23.3 vs 12.3±18.3 days, respectively, p=0.287). At 90 days, the composite rate of recurrence and major bleeding occurred in 37 (7%) of patients treated with reperfusion treatment and in 139 (9%) of untreated patients (p=0.127). Twenty-four (4%) reperfusion-treated patients and 82 (5%) untreated patients had early recurrence while major bleeding occurred in 13 (2%) treated and in 64 (4%) untreated patients, respectively. Seven patients in the untreated group experienced both an ischemic and hemorrhagic event. Figure 1 shows the risk of early recurrence and major bleeding over time in patients treated and not treated with reperfusion treatments. The use of NOACs was associated with a favorable rate of the primary outcome compared to VKAs (Odd ratio 0.4, 95% Confidence Interval 0.3–0.7). Conclusions Reperfusion treatment did not influence the risk of early recurrence and major bleeding in patients with AF-related acute ischemic stroke who started anticoagulant treatment. Figure 1 Funding Acknowledgement Type of funding source: None

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