AF-related Ischemic Stroke Research Articles

Could the Early Detection of Atrial Fibrillation Reduce the Risk of Developing Dementia?

Atrial fibrillation (AF) and dementia are major global public health issues and share common risk factors, especially after the age of 65 and regardless of the presence of stroke. Despite accounting for potential confounders, AF appears to be an independent risk factor for cognitive decline and dementia. The mechanisms are likely to be multifactorial and may include AF-related ischemic stroke, cerebral hypoperfusion, microbleeds, systemic inflammation, genetic factors, and small vessel disease, leading to brain atrophy and white matter damage. The early aggressive management of AF and comorbidities may reduce the risk of dementia. Indeed, the early detection of AF-related cognitive impairment should allow for the early implementation of measures to prevent the development of dementia, mainly through integrative approaches involving the correction of risk factors and maintenance of rhythm control. Well-designed prospective studies are needed to determine whether early detection and AF treatment can prevent dementia and identify whether optimal integrative measures are effective in preventing cognitive impairment and dementia.

Evidence of the association between increased use of direct oral anticoagulants and a reduction in the rate of atrial fibrillation-related stroke and major bleeding at the population level (2012–2019)

BackgroundThe introduction of direct-acting oral anticoagulants (DOACs) has shown to decrease atrial fibrillation (AF)-related stroke and bleeding rates in clinical studies, but there is no certain evidence about their effects at the population level. Our aim was to assess changes in AF-related stroke and major bleeding rates between 2012 and 2019 in Andalusia (Spain), and the association between DOACs use and events rates at the population level. MethodsAll patients with an AF diagnosis from 2012 to 2019 were identified using the Andalusian Health Population Base, that provides clinical information on all Andalusian people. Annual ischemic and hemorrhagic stroke, major bleeding rates, and used antithrombotic treatments were determined. Marginal hazard ratios (HR) were calculated for each treatment. ResultsA total of 95,085 patients with an AF diagnosis were identified. Mean age was 76.1±10.2 years (49.7% women). An increase in the use of DOACs was observed throughout the study period in both males and females (p<0.001). The annual rate of ischemic stroke decreased by one third, while that of hemorrhagic stroke and major bleeding decreased 2–3-fold from 2012 to 2019. Marginal HR was lower than 0.50 for DOACs compared to VKA for all ischemic or hemorrhagic events. ConclusionsIn this contemporary population-based study using clinical and administrative databases in Andalusia, a significant reduction in the incidence of AF-related ischemic and hemorrhagic stroke and major bleeding was observed between 2012 and 2019. The increased use of DOACs seems to be associated with this reduction.

Time trends in atrial fibrillation-related stroke during 2001-2020 in Sweden: a nationwide, observational study.

Great efforts have been made to improve stroke prevention in atrial fibrillation (AF) patients. Meanwhile, incidence of AF is increasing, which may affect the share of AF-related stroke on all strokes. We aimed to examine the temporal trends in the incidence of AF-related ischemic stroke between 2001 and 2020, if it varied by use of novel oral anticoagulant drugs (NOAC), and if the relative risk of ischemic stroke associated with AF changed over time. Data from the total Swedish population aged ≥70 years during the period 2001-2020 were used. Annual incidence rate (IR) was calculated for overall and AF-related ischemic stroke which was defined as first-ever ischemic stroke with AF diagnosed up to 5 years before, on the same day, or within 2 months after the stroke event. Cox regression models were performed to examine if the hazard ratio (HR) between AF and stroke changed over time. While IR of ischemic strokes declined during 2001-2020, IR of AF-related ischemic stroke remained stable between 2001 and 2010 but showed a consistent decline between 2010 and 2020. The HR of ischemic stroke within 3 years from an AF diagnosis came down from 2.39 (95% confidence interval: 2.31-2.48) to 1.54 (1.48-1.61) over the study period, which was largely explained by a substantial increase in the use of NOAC among AF patients after 2012. Yet, by the end of 2020, 24% of all ischemic strokes had a preceding or concurrent AF diagnosis, which is slightly higher than in2001. Even though both the absolute and relative risk of AF-related ischemic stroke declined over the past 20 years, every fourth ischemic stroke in 2020 still had a preceding or concurrent AF diagnosis. This represents a great potential for future gains in stroke prevention among AF patients. Swedish Research Council and Loo and Hans Osterman Foundation for Medical Research.

Echocardiographic correlates of MRI imaging markers of cerebral small-vessel disease in patients with atrial-fibrillation-related ischemic stroke.

Atrial fibrillation (AF) has been linked to dementia risk, partly explained by cerebral small vessel disease (CSVD). Since AF and cardiovascular comorbidities were associated with cardiac dysfunction, we aimed to determine the association between echocardiographic parameters and neuroimaging markers of CSVD in patients with AF-related ischemic stroke. This cross-sectional study enrolled patients with AF-related ischemic stroke from March 2013 to December 2019 who underwent transthoracic echocardiography and brain 3T MRI, including T1, T2, Flair, and SWI imaging sequences. We assessed the presence of lacunes and cerebellar microbleeds (CMBs), the severity of white matter hyperintensity (WMH) scored by the Fazekas scale (0-6), and the severity of enlarged perivascular spaces (EPVS) in basal ganglia (BG) and centrum semiovale (CSO) classified into three categories (0-10, 10-25, and >25). CSVD burden was rated on a 0-to-4 ordinal scale. Generalized linear regression analysis and post hoc comparisons with Bonferroni correction were performed to assess the association between various echocardiographic parameters and these lesions, adjusted for demographics and potential confounders. 119 patients (68.38 ± 12.692 years; male 45.4 %) were included for analysis, of whom 55 (46.2%) had lacunes, 40 (33.6%) had CMBs, and median severity for WMH, BG-EPVS, CSO-EPVS, and CSVD burden were 2 (IQR: 1-3), 1 (IQR: 1-2), 1 (IQR: 0-1), and 1 (IQR: 1-2) respectively. In multivariable, fully adjusted models, left ventricular posterior wall thickness (LVPW) was associated with a higher risk of lacunes (RR 1.899, 95% CI: 1.342-2.686) and CSVD burden (RR = 2.081, 95%CI: 1.562-2.070). Right atrial diameter (RAD) was associated with greater CSO-EPVS (RR = 2.243, 95%CI: 1.234-4.075). No echocardiographic parameters were revealed to be associated with CMBs and WMH. In patients with AF-related ischemic stroke, LVPW is associated with a higher risk of lacunes and CSVD burden, while RAD was associated with greater CSO-EPVS. Larger studies are required to determine these associations and to elucidate if these associations can help facilitate cognitive evaluation and brain MRI screening.

Timing of Anticoagulation after Acute Ischemic Stroke in Patients with Atrial Fibrillation.

Patients with atrial fibrillation (AF) and ischemic stroke are at high risk for stroke recurrence. Early anticoagulation may reduce the risk of recurrent events but is usually avoided due to the risk of hemorrhagic transformation (HT). Current guidelines are based on empiric expert opinion. The assumed risk of HT is based on historical data from an older generation of anticoagulants. The direct oral anticoagulants (DOACs) have demonstrated lower risk of intracranial hemorrhage compared to older anticoagulants. However, the optimal timing of DOAC initiation after AF-related ischemic stroke has remained an area of clinical equipoise, as the pivotal phase III trials did not include patients in the early period after ischemic stroke. Multiple prospective studies and a few smaller randomized controlled trials evaluating the safety and efficacy of early versus delayed DOAC initiation have been completed. These studies have reported promising results of early DOAC initiation after acute ischemic stroke. However, a standardized documentation of HT rates on follow-up imaging with objective assessment criteria is missing from most of these studies. Larger randomized trials of early versus delayed DOAC are ongoing. A literature review was performed using keywords and Medical Subject Headings in MEDLINE/PubMed and Google Scholar databases. For each relevant paper, the bibliography was scrutinized for other relevant articles and journals. In this article, we review the risk of recurrent ischemic stroke and HT in patients with AF, pathophysiology, classification, predictors, natural history, and outcomes of HT and discuss the studies of early anticoagulation after AF-related ischemic stroke.

Analyzing Corin-BNP-NEP Protein Pathway Revealing Differential Mechanisms in AF-Related Ischemic Stroke and No AF-Related Ischemic Stroke.

BackgroundThe incidence of atrial fibrillation (AF)-related stroke increases with aging. Natriuretic peptides (NPs) family, including Corin-B type natriuretic peptide (BNP)-neprilysin (NEP) protein levels increased with age and are risk markers of cardiovascular and cerebrovascular diseases, such as AF and cardioembolic stroke. Aging is also linked to epigenetics, specifically DNA methylation. However, only a few studies have investigated the effect of DNA methylation on the NP system. Thus, the present study aimed to investigate whether the Corin-BNP-NEP protein pathway is involved in the pathogenesis of AF-stroke and CpG methylation in the promoter region of the Corin protein gene has an effect on AF-related ischemic stroke.MethodsA total of 82 patients hospitalized with acute ischemic strokes were enrolled in this study. The differences in clinical information were compared between the AF-stroke (n = 37) and no AF-stroke groups (n = 45). Plasma-soluble Corin and NEP were detected using an ELISA kit. CpG methylation in the promoter region of the gene was assessed by a next-generation sequencing-based bisulfite sequencing polymerase chain reaction (BSP).Results(1) Patients in AF-stroke were older, had higher initial NIHSS score, 90-day mRs, higher D2-dimer, INR, and APTT, and low TG, TC, and HbA1c (all p < 0.05). (2) Serum levels of Corin and BNP in the AF-stroke group were significantly higher than that in the no AF-stroke group (p < 0.05). No significant difference was detected in the serum levels of NEP between the two groups. (3) The levels of CpG methylation in the promoter region of the Corin protein gene in the AF-stroke group was significantly lower than that in the no AF-stroke group (p < 0.05). The CpG sites with maximal methylation differences between the two groups were CORIN:678, CORIN:682, CORIN:694, and CORIN:700.ConclusionThe current findings raise the possibility that the Corin–BNP–NEP protein pathway may be involved in the pathogenesis of AF-related ischemic stroke. Deficient CpG methylation in the promoter region of the Corin protein gene is associated with AF-related ischemic stroke.

Abstract TP189: Atrial Fibrillation, Age, And Ischemic Stroke Severity In A Nationally Representative Dataset

Introduction: Atrial fibrillation (AF), a well-defined ischemic stroke (IS) risk factor whose prevalence increases with age, is associated with higher stroke severity. We aimed to evaluate stroke severity and hospital mortality in a nationally representative sample of AF-related IS patients. Methods: We utilized data from the National (Nationwide) Inpatient Sample databases from 2015 - 2018 using ICD-10 diagnostic codes to identify individuals with IS and comorbid AF. The NIHSS was used to characterize stroke severity in a subset of cases after 10/1/2016. Nonparametric statistics and logistic regression analyses were conducted to evaluate associations between AF and hospital death. Results: Of the 382,758 IS cases, 99,566 (26%) had comorbid AF. AF increased linearly with age, reaching at 47% of all hospitalized IS patients 85+ years of age or older (Figure). Higher age, male sex, white race, obesity, and higher median income were associated with comorbid AF, whereas diabetes, hypertension, tobacco use, and hyperlipidemia were associated with reduced odds of comorbid AF. While 5.8% of all IS patients died during hospitalization, mortality was increased nearly two-fold in those with AF (9.0% vs. 4.6%, p&lt;.001). Among in-hospital deaths from IS, comorbid AF increased with age, present in 59% of those 85+ years of age or older (Figure). NIHSS, reported in 21% of patients, was higher in AF patients (mean NIHSS 6 vs. 9, p&lt;.001). High NIHSS was the strongest independent predictor of hospital death. Conclusion: The burden of AF in a nationally representative sample of hospitalized IS patients is substantial, present in nearly 50% of the 85+ age group. AF-related IS is more severe and more likely to be fatal. As our population ages, the prevalence of AF will only increase. Understanding the severity and fatality of AF-related IS will have profound implications for health systems and may better facilitate anticipatory guidance and AF treatment.

Epidemiología del ictus cardioembólico y su asociación con la penetración de los ACOD en España: primer estudio poblacional 2005-2018

Introduction and objectivesThe incidence and prevalence of atrial fibrillation (AF), a major risk factor for stroke, has increased substantially in the past few years. However, several studies have reported a decline in AF-related stroke rates associated with higher uptake of direct oral anticoagulants (DOACs). This ecological study evaluated the association between DOAC uptake in Spain and the incidence rate (IR) of AF-related ischemic stroke. MethodsData were obtained from the Registry of Activity of Specialized Healthcare of the Spanish Ministry of Health (RAE-MDS). AF-related ischemic strokes were identified using International Classification of Diseases codes. IR were age-standardized and adjusted to the 2013 European standard population. Poisson regression models were used to identify the association between DOAC uptake and AF-related ischemic stroke in patients aged ≥ 65 years. ResultsBefore the use of DOACs, the adjusted IR of AF-related ischemic stroke increased steadily from 2005 (IR=2.20 per 100 000 person/y) to 2012 (IR=2.67). Upon DOAC uptake in Spain from 2012 onwards for AF-related ischemic stroke prevention, the IR remained constant or decreased slightly (IR in 2018=2.66). Poisson regression showed that DOAC uptake was a significant predictor for the rate of AF-related ischemic stroke in patients older than 65 years (IRR=0.995; 95%CI, 0.995-0.996). ConclusionsThis study shows an association between DOAC use and a reduced incidence of AF-related ischemic stroke. While this association is based on aggregate data and cannot demonstrate causality, these findings suggest that higher DOAC uptake could improve health outcomes in AF patients in Spain.Full English text available from:www.revespcardiol.org/en

Epidemiology of atrial fibrillation-related ischemic stroke and its association with DOAC uptake in Spain: first national population-based study 2005 to 2018

Introduction and objectivesThe incidence and prevalence of atrial fibrillation (AF), a major risk factor for stroke, has increased substantially in the past few years. However, several studies have reported a decline in AF-related stroke rates associated with higher uptake of direct oral anticoagulants (DOACs). This ecological study evaluated the association between DOAC uptake in Spain and the incidence rate (IR) of AF-related ischemic stroke. MethodsData were obtained from the Registry of Activity of Specialized Healthcare of the Spanish Ministry of Health (RAE-MDS). AF-related ischemic strokes were identified using International Classification of Diseases codes. IR were age-standardized and adjusted to the 2013 European standard population. Poisson regression models were used to identify the association between DOAC uptake and AF-related ischemic stroke in patients aged ≥ 65 years. ResultsBefore the use of DOACs, the adjusted IR of AF-related ischemic stroke increased steadily from 2005 (IR=2.20 per 100 000 person/y) to 2012 (IR=2.67). Upon DOAC uptake in Spain from 2012 onwards for AF-related ischemic stroke prevention, the IR remained constant or decreased slightly (IR in 2018=2.66). Poisson regression showed that DOAC uptake was a significant predictor for the rate of AF-related ischemic stroke in patients older than 65 years (IRR=0.995; 95%CI, 0.995-0.996). ConclusionsThis study shows an association between DOAC use and a reduced incidence of AF-related ischemic stroke. While this association is based on aggregate data and cannot demonstrate causality, these findings suggest that higher DOAC uptake could improve health outcomes in AF patients in Spain.

The association between increasing oral anticoagulant prescribing and atrial fibrillation related stroke in Ireland.

Recent increases in the number of patients with atrial fibrillation (AF) prescribed oral anticoagulants (OAC) are evident in Ireland and internationally, largely due to the availability of direct oral anticoagulants (DOACs). This study aimed to determine the rate of stroke in the context of increasing anticoagulation utilisation, with a focus on AF-related ischaemic stroke (IS). Dispensing data for OACs were identified for the period 2010-2018 as well as hospital discharges for IS (2005-2018). Irish National Stroke Register data were used to elucidate the characteristics of patients with acute ischaemic stroke. The number of patients prescribed OACs increased by 94% from 2010-2018 with a significant change from 2013 (β = 2.57, P = .038), associated with a large increase in the number of patients on DOACs. There was 3.3-fold increase in expenditure on OACs nationally from 2013 to 2018, of which 94% was DOAC related. Using the 2013 timepoint, ischaemic stroke rates until 2018 did not show a significant deviation from the previous trend (β = 0.00, P = .898). The percentage of AF-related ischaemic stroke was stable from 2013 to 2017 with a 4.5% decrease in 2018. The percentage of ischaemic stroke patients with previously diagnosed AF decreased from 2013 to 2018; however, there was an increase in the percentage of ischaemic strokes while on OAC in this cohort. Large increases in OAC utilisation have not resulted in changes in ischaemic stroke rates at a national level. The percentage of ischaemic strokes with a previous diagnosis of AF has decreased indicating a possible benefit from greater OAC utilisation. However, the percentage presenting with an ischaemic stroke while on OAC treatment is increasing. The increase in patients presenting with stroke while treated with OAC may largely reflect the national increase in patients prescribed DOACs but the findings raise concerns about treatment failures. The real-world effectiveness of DOACs requires further examination.

Prestroke Statins Improve Prognosis of Atrial Fibrillation-Associated Stroke through Increasing Suppressor of Cytokine Signaling-3 Levels

Background: Cerebral infarction associated with atrial fibrillation (AF) has relatively higher mortality and morbidity rates than other types of stroke. Statins are being commonly prescribed to patients with stoke. However, the use of statins in AF-related stroke, especially prestroke, has not been well studied. This study aimed to investigate whether the use of prestroke statins could improve clinical outcomes in patients with AF-related acute ischemic stroke (AIS) and its mechanism. Methods: This prospective study enrolled 453 AF-associated AIS patients from 4 medical centers and divided them into 2 groups based on the statin use before the stroke episode. All patients received comprehensive clinical examinations including 72-h Holter electrocardiogram monitoring and were followed up for 3 months. Plasma suppressor of cytokine signaling-3 (SOCS-3) and matrix metalloproteinase-9 (MMP-9) levels were measured by ELISA on admission and days 3 and 7 after enrollment. The endpoints were death, major disability (modified Rankin Scale score ≥3), and composite outcome (death/major disability) at 3 months after the AIS episode. Results: Plasma SOCS-3 levels were significantly increased and MMP-9 levels decreased in patients in the prestroke statin group on hospital admission and days 3 and 7 after enrollment (p < 0.001). Furthermore, our data suggested that baseline plasma SOCS-3 levels were associated with increased risk of 3-month mortality (adjusted odds ratio [OR], 1.012; 95% confidence interval [CI], 1.006–1.018; p < 0.001) and major disability (adjusted OR, 1.013; 95% CI, 1.007–1.02; p < 0.001). Similarly, baseline plasma MMP-9 levels were also associated with increased risk of 3-month mortality (adjusted OR, 1.037; 95% CI, 1.022–1.053; p < 0.001) and major disability (adjusted OR, 1.038; 95% CI, 1.022–1.55; p < 0.001). Conclusion: Our data suggested that the prestroke use of statins improved the clinical outcomes in AIS patients with AF by upregulating the level of SOCS-3 and reducing the plasma MMP-9 level.

Abstract P617: Ischemic Strokes in Patients With Atrial Fibrillation: The Neuro-AFib Study

Background: An estimated 150,000 atrial fibrillation (AF) patients suffer an ischemic stroke (IS) annually in the US. Understanding the frequency/causes of underuse and failures of current FDA-approved preventive methods in patients with known AF may reduce stroke risk and related death/disability. Methods: The Neuro-AFib study is a multicenter effort geared toward elucidating the causes and consequences of IS and hemorrhagic stroke (HS) in a contemporary AF cohort. The retrospective phase of the study is underway, aiming to obtain detailed clinical, laboratory and multimodal neuro- and cardiac imaging data from ~9,000 AF patients admitted to 30 US academic stroke centers with an IS or HS between 1/2018-12/2019. Clinical data of IS admissions from 12 sites will be discussed. Disability is defined as a modified Rankin Score (mRS) 3-5, outcomes are from the time of hospital discharge. Results: A total of 3944 AF patients presented with an IS, mean age was 76.8 + 12, and 50.2% were female. AF was diagnosed prior to IS in 78% of patients. Data on prestroke antithrombotic usage, embolic risk scores, clinical stroke severity and outcomes are presented in the FIGURE. Conclusions: Preliminary results from the Neuro-AFib study show high rates of underuse of approved stroke prevention measures (54%) and anticoagulant failures (46%) that result into IS even in known AF patients. Relatively high rates of pre-stroke AF detection failures were also noted (22%). Death/disability rates were high in all of these AF-related IS patients ( &gt; 69%). Detailed data collection focused on imaging and lab markers of stroke risk from this contemporary cohort will be ready to be presented during ISC 2021.

Impact of prescription patterns of antithrombotic treatment on atrial fibrillation-related ischemic stroke

Objective To analyze the temporal trends of atrial fibrillation (AF)-related ischemic stroke (IS) and their relationship with the prescription patterns of antithrombotic treatment from 2013 to 2019 in the Health Assistance Area of a regional hospital. Methods First, a retrospective ecological study of aggregate data to analyze the annual incidence of IS between 2013 and 2019 was performed. Second, we selected those patients diagnosed with AF between 2013 and 2019 and performed a retrospective longitudinal study to assess the role of antithrombotic therapy in the development of AF-related IS. Results During this period, whereas the annual incidence of IS remained stable (from 1.3 in 2013 to 1.2 cases per 1000 inhabitants in 2019; adjusted P for trend .829), the annual incidence of AF-related IS decreased over time (from 23.8 to 18.8 cases per 1000 inhabitants, respectively; adjusted P for trend .001). Among AF patients, the use of direct oral anticoagulants increased from 5.5% to 46.8%, while the prescription of antiplatelets and vitamin K antagonists decreased from 21.9% to 6.0% and from 63.8% to 36.1%, respectively. Overall, the use of oral anticoagulants increased from 69.3% to 82.9%; p < .001. Patients under antiplatelet agents had a higher probability of presenting IS than those patients taking oral anticoagulants, either vitamin K antagonists or direct oral anticoagulants (adjusted OR 1.89; 95% CI 1.52–2.37; p < .001). Conclusions The prescription of oral anticoagulants, particularly direct oral anticoagulants, has increased from 2013 to 2019 in our Health Assistance Area. This increase might partially explain the reduction in AF-related IS.

Ischemic stroke with Atrial Fibrillation, characteristics and time-trends over 12-year period 2006-2017 in the Dijon Stroke Registry

Because of the aging population, an increase in the prevalence of atrial fibrillation (AF) is currently observed, thus exposing to a rise in AF-related ischemic stroke (IS). The aim was to analyze the current prevalence of AF among IS patients (period 2014-17), their characteristics, and temporal trends from 2006 to 2017, in the population-based Dijon Stroke Registry. We used data from the Dijon Stroke Registry. IS patients were included between 2006 and 2017 ( n = 2,417). Vascular risk factors and past medical history were collected, including AF. “Previous AF” was defined if it was mentioned in the medical file before stroke, and “newly-diagnosed AF” if it was diagnosed during the diagnostic work-up of the acute stroke. We assumed Poisson distribution for the annual number of AF cases. During the period 2014-2017, over the 796 IS patients recorded in the Dijon Stroke Registry, 239 (30.0%) had AF, of whom 79 (9.9% of IS patients) had newly-diagnosed AF and 98 (12.3%) had previous AF treated with oral anticoagulants. IS patients with AF had more disabilities and a higher initial severity according to the NIHSS score compared to those without AF. AF patients had also more frequent hypercholesterolemia and heart failure. The age-adjusted prevalence of AF in IS patients increased between 2006 and 2017 (+ 9% per time period), with an important increase in men aged 65-74 (+ 81%) and women aged ≥ 85 (+ 24%) years old, and a significant decrease in women aged 65-74years old (-39%). The use of oral anticoagulant treatment in previous AF patients increased between 2006-2009 and 2014-2017 (29.3% to 61.3%, P < 0.0001). The increase in AF prevalence in IS patients could be related to a better diagnosis of this condition. Despite some improvements, an underuse of oral anticoagulation in patients with previously known AF was still observed, thus indicating a prevention target on which to act to reduce the future burden of stroke.

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

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

Anticoagulation decisions in elderly patients with stroke

Primary and secondary prevention of stroke is often a challenge in elderly patients due to the increase in both thrombotic and hemorrhagic risks with age. In some cases, there is sufficient data in the elderly population to allow recommendations or anticoagulation decisions to be made, such as for the indication of anticoagulation to prevent stroke related to atrial fibrillation (AF) or the choice of oral anticoagulant therapy in this situation. In other situations, the less robust data leave some questions; this is the case for the delay to initiate an oral anticoagulant therapy after an AF-related ischemic stroke, for the management of antithrombotic treatment after a stroke of undetermined cause or after intracranial bleeding or in a high-risk bleeding situation associated with stroke in the elderly subject. These issues will be discussed in this paper.

Red Cell Distribution Width and Risk of Atrial Fibrillation and Subsequent Thromboembolism: The Tromsø Study.

Introduction Red cell distribution width (RDW) is associated with cardiovascular diseases, including atrial fibrillation (AF) and venous thromboembolism (VTE). Whether RDW is a risk marker for thromboembolic events in AF patients is scarcely known. We aimed to assess the association between RDW and the risk of AF, and AF-related VTE and ischemic stroke, in a population-based cohort. Methods We measured RDW in 26,111 participants from the Tromsø Study (1994–1995), and registered incident AF cases through December 31, 2013. Among participants with AF, first-ever VTEs and ischemic strokes were registered from the date of AF diagnosis through the end of follow-up. We calculated hazard ratios (HRs) with 95% confidence intervals (CIs) for AF by quartiles of RDW. Furthermore, we calculated cause-specific HRs for VTE and ischemic stroke by tertiles of RDW for participants with AF. Results There were 2,081 incident AF cases during a median of 18.8 years of follow-up. Subjects with RDW in the highest quartile (RDW ≥ 13.3%) had 30% higher risk of AF than those in the lowest quartile (RDW ≤ 12.3%). Among those with AF, subjects with RDW in the upper tertile had a doubled risk of ischemic stroke (HR 2.07, 95% CI 1.20–3.57). In contrast, RDW was not associated with incident VTE in subjects with AF. Conclusion RDW was significantly associated with incident AF in a general population. Among subjects with AF, high RDW was associated with ischemic stroke, but not VTE.

Abstract TMP18: Early versus Late Start of Direct Oral Anticoagulants After an Ischemic Stroke Related to Atrial Fibrillation - An Individual Patient Data Analysis

Background: The optimal timepoint of starting DOAC after an acute ischemic stroke (IS) related to atrial fibrillation (AF) remains unclear. We aimed to compare an early (≤ 5 days of IS) versus late (&gt;5 days of IS) DOAC-start. Methods: Individual patient data analysis of 7 European and Japanese prospective observational cohort studies. We included patients with IS or TIA related to non-valvular AF where a DOAC was started within 30 days. We excluded patients with an intracranial bleeding (ICH) after the index event but prior to DOAC-start. We compared the 30-day rates of recurrent IS and ICH between the groups of early versus late DOAC-start with a landmark analysis at day 5. Results: Overall, 2550 patients were included. Median age was 77 years (IQR 70-84). DOAC were started early in 1362 (53%) patients, late in 1188 (47%). In the whole cohort, 37 patients suffered from a recurrent IS (1.5%), 16 patients (43%) of whom before any DOAC was started. 6 patients (0.2%) had an ICH. In the early DOAC-start group, 23 patients (1.7%) suffered from a recurrent IS after DOAC-start and within 30 days; two patients (0.1%) suffered from ICH after DOAC-start. In the late DOAC-start group, 14 patients (1.2%) suffered from a recurrent IS before DOAC was started; 4 patients (0.3%) suffered from ICH after DOAC-start. In the comparison of late versus early DOAC-groups, no difference in the hazard ratios was observed for the endpoint of recurrent IS (HR = 1.15, 95%CI 0.48-2.73, p=0.76) and ICH (HR = 4.71, 95%CI 0.51-43.10, p=0.17). Conclusion: Our results do not corroborate the concern that early anticoagulation - at least when performed with DOACs - increases the risk of hemorrhagic transformation of the brain infarct compared to late anticoagulation. Given the seven times higher risk of recurrent IS - with almost half of recurrent IS occurring before any DOAC-start - an early DOAC-start after AF-related IS may be reasonable, if inclusion in the ongoing trials (the recommended option) is not possible.

Impact of atrial fibrillation burden on cognitive function after left atrial ablation – Results of the MACPAF study

Atrial fibrillation (AF) is associated with cognitive decline and dementia irrespective of AF-related ischemic stroke. We investigated whether AF burden after ablation in patients with symptomatic paroxysmal AF has an impact on cognitive function. After enrolment to the prospective MACPAF study, study patients received an insertable loop recorder (ILR) and underwent serial neurological/cognitive assessment. To compare cognitive function, the delta of baseline and six months test results (Δpre/post) and a score to assess overall cognitive performance were computed. Thirty patients (median age 65 years (IQR 57–69), 40% female) were divided into groups according to median AF burden (<0.5% vs. ≥0.5%) after ablation. Overall cognitive performance did not differ in patients with an AF burden < 0.5% (median 120% [IQR 100–150]) vs. ≥0.5% (median 120% [IQR 100–160]) within six months after ablation (p = 0.74). Comparing Δpre/post, patients with an AF burden ≥ 0.5% showed significantly better results in the digit-span backwards test (median + 1 [IQR 0 - +2 points]) compared to patients with an AF burden < 0.5% (median 0 [IQR −1–+1]) six months after ablation (p = 0.03). In patients with an AF burden < 0.5%, there was a statistical trend towards better results in the RAVLT test (median + 3 [IQR 0–+4]; p = 0.08) and the ROC test (median + 3 [IQR −1–+5; p = 0.07) compared to patients with an AF burden ≥ 0.5% (median −1 [IQR −3–+2] words and median −1 [IQR −5–+2] points, respectively). Therefore, AF burden had no significant impact on cognitive performance within six months after ablation.Clinical Trial Registration: clinicaltrials.gov NCT01061931.

Prestroke statins use reduces oxidized low density lipoprotein levels and improves clinical outcomes in patients with atrial fibrillation related acute ischemic stroke

BackgroundAtrial fibrillation (AF) is a common cause of cerebral infarction, which could lead to endothelial dysfunction, increased reactive oxygen species (ROS) and oxidized low density lipoprotein (Ox-LDL).AF is associated with higher mortality and more severe neurologic disability. Statins may exert neuroprotective effects that are independent of LDL-C lowering. The purpose of our study was to investigate whether prestroke statins use could reduce plasma Ox-LDL levels and improve clinical outcomes in patients with AF-related acute ischemic stroke (AIS).MethodsThis was a multicenter prospective study that involved four medical centers, 242 AIS patients with AF were identified, who underwent a comprehensive clinical investigation and a 72 h-Holter electrocardiogram monitoring. All patients were divided into two groups: prestroke statins use and no prestroke statins use groups, who were followed up for 3 months. Plasma Ox-LDL levels were measured using enzyme-linked immunosorbent assay (ELISA) on admission and at 3 months. The outcome was death, major disability (modified Rankin Scale score ≥ 3), and composite outcome (death/major disability) at 3 months after AIS.ResultsOne hundred thirty-six patients were in no prestroke statins use group, and 106 in prestroke statins use group. Plasma Ox-LDL levels were significantly lower in prestroke statins use than in no prestroke statins use on admission and at 3 months (P < 0.001). Plasma Ox-LDL levels on admission were associated with 3-month mortality [adjusted odds ratio (OR), 1.05; 95% confidence interval (CI), 0.99–1.12; P = 0.047]. In fully adjusted models, prestroke statins use was associated with reduced 3-month mortality [adjusted OR, 0.38; 95% CI, 0.16–0.91; P = 0.031)], major disability (adjusted OR, 0.38; 95% CI, 0.15–0.99; P = 0.047), and composite outcome (adjusted OR, 0.31; 95% CI, 0.17–0.74; P = 0.009).ConclusionsPrestroke statins use can reduce plasma Ox-LDL levels and improve clinical outcomes in patients with AF-related AIS.