Multicenter randomized study of anticoagulation guided by remote rhythm monitoring in patients with implantable cardioverter-defibrillator and CRT-D devices: Rationale, design, and clinical characteristics of the initially enrolled cohort The IMPACT study. Probing oral anticoagulation in patients with atrial high rate episodes: Rationale and design of the Non–vitamin K antagonist Oral anticoagulants in patients with Atrial High rate episodes (NOAH–AFNET 6) trial Patient knowledge and perceptions of atrial fibrillation and anticoagulant therapy: effects of an educational intervention programme. The West Birmingham Atrial Fibrillation Project. Focused 2012 update of the Canadian Cardiovascular Society atrial fibrillation guidelines: recommendations for stroke prevention and rate/rhythm control. Prevalence of atrial fibrillation and eligibility for anticoagulants in the community Factors affecting bleeding risk during anticoagulant therapy in patients with atrial fibrillation: observations from the Atrial Fibrillation Follow-up Investigation of Rhythm Management (AFFIRM) study. Prevalence, clinical profile, and cardiovascular outcomes of atrial fibrillation patients with atherothrombosis. Rationale and design of the Apixaban for the Reduction of Thrombo‐Embolism in Patients With Device‐Detected Sub‐Clinical Atrial Fibrillation (ARTESiA) trial Transesophageal echocardiographic correlates of thromboembolism in high-risk patients with nonvalvular atrial fibrillation. The Stroke Prevention in Atrial Fibrillation Investigators Committee on Echocardiography. Does left atrial appendage closure with a cardiac plug system reduce the stroke risk in nonvalvular atrial fibrillation patients? A single-center case series. Acute stroke with atrial fibrillation. The Copenhagen Stroke Study. Anemia is associated with bleeding and mortality, but not stroke, in patients with atrial fibrillation: Insights from the Apixaban for Reduction in Stroke and Other Thromboembolic Events in Atrial Fibrillation (ARISTOTLE) trial Major progress in anticoagulant uptake for atrial fibrillation at last: does it translate into stroke prevention? Is screening for AF worthwhile? Stroke risk in a screened population from the SAFE study. Antithrombotic therapy in elderly patients with atrial fibrillation: effects and bleeding complications: a stratified analysis of the NASPEAF randomized trial. [Study of combined anticoagulant (fluindione)-aspirin therapy in patients with atrial fibrillation at high risk for thromboembolic complications. A randomized trial (FFAACS)]. Effect of Age on Stroke Prevention Therapy in Patients With Atrial Fibrillation: The Atrial Fibrillation Investigators
Atrial fibrillation and atrial flutter are common cardiac arrhythmias associated with an increased risk of stroke in patients with additional risk factors .  Anticoagulation ameliorates stroke risk , but because these arrhythmias may occur intermittently without symptoms , initiation of prophylactic therapy is often delayed until electrocardiographic documentation is obtained . The IMPACT study is a multicenter , r and omized trial of remote surveillance technology in patients with implanted dual-chamber cardiac resynchronization therapy defibrillator ( CRT-D ) devices design ed to test the hypothesis that initiation and withdrawal of oral anticoagulant therapy guided by continuous ambulatory monitoring of the atrial electrogram improve clinical outcomes by reducing the combined rate of stroke , systemic embolism , and major bleeding compared with conventional clinical management . For those in the intervention group , early detection of atrial high-rate episodes ( AHRE ) generates an automatic alert to initiate anticoagulation based on patient-specific stroke risk stratification . Subsequently , freedom from AHRE for predefined periods prompts withdrawal of anticoagulation to avoid bleeding . Patients in the control arm are managed conventionally , the anticoagulation decision prompted by incidental detection of atrial fibrillation or atrial flutter during routine clinical follow-up . The results will help define the clinical utility of wireless remote cardiac rhythm surveillance and help establish the critical threshold of AHRE burden warranting anticoagulant therapy in patients at risk of stroke . In this report , we describe the study design and baseline demographic and clinical features of the initial cohort ( 227 patients ) Background Oral anticoagulation prevents ischemic strokes in patients with atrial fibrillation ( AF ) . Early detection of AF and subsequent initiation of oral anticoagulation help to prevent strokes in AF patients . Implanted cardiac pacemakers and defibrillators allow seamless detection of atrial high rate episodes ( AHRE ) , but the best antithrombotic therapy in patients with AHRE is not known . Rationale Stroke risk is higher in pacemaker patients with AHRE than in those without , but the available data also show that stroke risk in patients with AHRE is lower than in patients with AF . Furthermore , only a minority of patients with AHRE will develop AF , many strokes occur without a temporal relation to AHRE , and AHRE can reflect other arrhythmias than AF or artifacts . An adequately powered controlled trial of oral anticoagulation in patients with AHRE is needed . Design The Non – vitamin K antagonist Oral anticoagulants in patients with Atrial High rate episodes ( NOAH – AFNET 6 ) trial tests whether oral anticoagulation with edoxaban is superior to prevent the primary efficacy outcome of stroke or cardiovascular death compared with aspirin or no antithrombotic therapy based on evidence ‐based indications . The primary safety outcome will be major bleeding . NOAH – AFNET 6 will r and omize 3,400 patients with AHRE , but without documented AF , aged ≥65 years with at least 1 other stroke risk factor , to oral anticoagulation therapy ( edoxaban ) or no anticoagulation . All patients will be followed until the end of this investigator‐driven , prospect i ve , parallel‐group , r and omized , event‐driven , double‐blind , multicenter phase IIIb trial . Patients will be censored when they develop AF and offered open‐label anticoagulation . The sponsor is the Atrial Fibrillation NETwork ( AFNET ) . The trial is supported by the DZHK ( German Centre for Cardiovascular Research ) , the BMBF ( German Ministry of Education and Research ) , and Daiichi Sankyo Europe . Conclusion NOAH – AFNET 6 will provide robust information on the effect of oral anticoagulation in patients with atrial high rate episodes detected by implanted devices . Graphical abstract Figure . No Caption available OBJECTIVE Previous research has demonstrated that patients with atrial fibrillation ( AF ) possess very little knowledge of their disease , the consequences of AF and the benefits /risks of anti-coagulant therapy . The aim of this pilot study was to examine patient 's knowledge and perceptions of AF and their anticoagulant treatment before and after a brief educational intervention . MATERIAL S AND METHODS Ninety-three patients ( 47 male ; mean ( S.D. ) age 67.3 ( 11.6 ) years ) completed the baseline interview to assess their knowledge and perceptions of AF . All patients were given an information booklet which explained what AF was , associated symptoms , the possible causes and consequences of AF , treatment options and their benefits /risks , what the INR is and what factors may effect it . The booklet was explained to each patient by the research er and given to the patient to take away for reference . Thirty-three ( 35.5 % ) patients ( 12 men ; mean ( S.D. ) age 68.0 ( 13.6 ) years ) completed the follow-up assessment to re-assess their knowledge and perceptions of AF . RESULTS Only 49 % of patients could name their cardiac condition at baseline , although the majority were aware that AF was an arrhythmia ( 80 % baseline vs. 91 % follow-up ) . Only about half the patients perceived AF as a serious condition or were aware that AF predisposes to thromboembolism at baseline . Following the educational intervention there was a non-significant increase in patient knowledge of the risks associated with AF . Of those who completed both question naires , 52 % were aware that anticoagulants prevented blood clots , which increased to 70 % post-intervention . However , few patients were aware of the benefit of stroke prevention associated with anticoagulants at baseline ( 21 % ) or after the educational intervention ( 27 % ) . The intervention had little effect on increasing awareness of the bleeding risks associated with anticoagulants , although three in five people appeared to appreciate these risks . However , the educational intervention significantly improved patient 's knowledge of the target INR range and factors that may affect INR levels ( p=0.001 and p=0.014 , respectively ) for those who completed both question naires . CONCLUSIONS Most patients with AF possess very limited knowledge about their cardiac condition , its consequences , and how anticoagulant treatment can benefit them . This pilot study has demonstrated that a brief educational intervention with an information booklet can help to somewhat improve their knowledge about anticoagulation therapy for AF The Canadian Cardiovascular Society ( CCS ) published the complete set of 2010 Atrial Fibrillation ( AF ) Guidelines in the January , 2011 issue of the Canadian Journal of Cardiology . During its deliberations , the CCS Guidelines Committee engaged to a timely review of future evidence , with periodic composition of focused up date s to address clinical ly important advances . In 2011 , results were published from 3 pivotal AF trials : the Rivaroxaban Once Daily Oral Direct Factor Xa Inhibition Compared with Vitamin K Antagonist for Prevention of Stroke and Embolism Trial in Atrial Fibrillation ( ROCKET-AF ) , the Apixaban for Reduction in Stroke and Other Thromboembolic Events in Atrial Fibrillation ( ARISTOTLE ) study , and the Permanent Atrial Fibrillation Outcome Study Using Dronedarone on Top of St and ard Therapy ( PALLAS ) , comparing dronedarone with placebo in patients with permanent AF and additional cardiovascular disease risk-factor burden . Each of these large r and omized trials provided clear results with major implication s for AF management . Other important evidence that has emerged since the 2010 Guidelines includes findings about prediction instruments for AF-associated stroke and bleeding risk , stroke risk in paroxysmal-AF patients , risk-benefit considerations related to oral anticoagulation in patients with chronic kidney disease , and risk/benefit considerations in the use of antiplatelet agents , alone and in combination with each other or with oral anticoagulants , in AF patients . The Guidelines Committee judged that this extensive and important new evidence required focused updating of the 2010 Guidelines with respect to stroke prevention and rate/rhythm control . This report presents the details of the new recommendations , along with the background and rationale BACKGROUND Anticoagulants are effective in the prevention of stroke in atrial fibrillation and flutter ( AF ) . We aim ed to find out the prevalence of AF in the UK and to estimate the proportion of patients with AF who might benefit from anticoagulation . METHODS We screened with electrocardiography a r and om sample of 4843 people from the community aged 65 years and older for AF . Participants with AF had further investigations to identify risk factors for stroke and contraindications to anticoagulants . We used three sets of criteria to assess risk and eligibility for anticoagulation . FINDINGS 228 ( 4.7 % ) participants had AF . According to analyses derived from risk stratifications based on the Stroke Prevention in Atrial Fibrillation ( SPAF ) study 61 % of these patients would have benefited from anticoagulation , 49 % according to pooled analysis of trial results , and 41 % according to the inclusion criteria for the SPAF 3 study .  Anticoagulants  were used by 1114 ( 23 % ) of all patients and were least used among elderly women , who may be the most likely to benefit . Echocardiography would be useful to assess the need for anticoagulation only in patients younger than 75 years with no contraindications to treatment and no clinical risk factors for stroke . INTERPRETATION Anticoagulants seem to be underused and misdirected in treatment of AF , according to various criteria . Efforts to promote and support wider and more appropriate use of anticoagulants would seem to be justified , and should decrease the incidence of stroke amongst elderly patients BACKGROUND Stroke and systemic thromboembolism are serious problems for patients with atrial fibrillation ( AF ) , but their incidence can be substantially reduced by appropriate anticoagulation . Bleeding is the major complication of anticoagulant treatment , and the relative risks for bleeding vs stroke must be considered when starting anticoagulation . METHODS The AFFIRM trial included patients with AF and at least one risk factor for stroke , r and omly assigning them to either a rate-control or rhythm-control strategy . All patients were initially treated with warfarin . The incidence of protocol -defined major and minor bleeding was documented during follow-up . Variables associated with bleeding were determined using a Cox proportional hazards model , using baseline and time-dependent covariates . RESULTS The 4060 patients in the AFFIRM trial were followed for an average of 3.5 years . Major bleeding occurred in 260 patients , an annual incidence of approximately 2 % per year , with no significant difference between the rate-control and rhythm-control groups . Increased age , heart failure , hepatic or renal disease , diabetes , first AF episode , warfarin use , and aspirin use were significantly associated with major bleeding . Minor bleeding was common in both treatment arms , with 738 patients reporting this problem in one or more visits . CONCLUSIONS Bleeding is a significant problem that complicates management of patients with AF . Risk factors for bleeding can be identified , and knowledge of these risk factors can be used to plan therapy BACKGROUND Atrial fibrillation ( AF ) is a major risk factor ( RF ) for ischemic stroke . Its prevalence and prognostic impact in patients with atherothrombosis are unclear . METHODS Risk factors , drug usage , and 1-year cardiovascular ( CV ) outcomes ( CV death , myocardial infa rct ion [ MI ] , and stroke ) were compared in  AF and non-AF patients from the REduction of Atherothrombosis for Continued Health ( REACH ) Registry , an international , prospect i ve cohort of 68,236 stable out patients with established atherothrombosis or > or=3 atherothrombotic RFs . RESULTS Atrial fibrillation and 1-year follow-up data are available for 63,589 patients . The prevalence of AF was , 12.5 % , 13.7 % , 11.5 % , and 6.2 % among coronary artery disease , CV disease , peripheral artery disease , and RF-only patients , respectively . Of the 6,814 patients with AF , 6.7 % experienced CV death , nonfatal MI , or nonfatal stroke within a year . The annual incidence of nonfatal stroke ( 2.4 % vs 1.6 % , P<.0001 ) and unstable angina ( 6.0 % vs 4.0 % , P<.00001 ) was higher , and CV death was more than double ( 3.2 % vs 1.4 % , P<.0001 ) , in AF versus non-AF patients . In these patients with or at high risk of atherothrombosis , most patients with AF received antiplatelet agents , but only 53.1 % were treated with oral anticoagulants . Even with high CHADS2 ( congestive heart failure , hypertension , aging , diabetes mellitus , and stroke ) scores , anticoagulant use did not exceed ( 59 % ) . The rate of bleeding requiring hospitalization was higher in AF versus non-AF patients ( 1.5 % vs 0.8 % , P<.0001 ) , possibly related to the more frequent use of anticoagulants ( 53.1 % vs 7.1 % ) . CONCLUSIONS Atrial fibrillation is common in patients with atherothrombosis , associated with more frequent fatal and nonfatal CV outcomes , and underuse of oral anticoagulants Background Device‐detected sub clinical atrial fibrillation ( AF ) refers to infrequent , short‐lasting , asymptomatic AF that is detected only with long‐term continuous monitoring . Sub clinical AF is common and associated with an increased risk of stroke ; however , the risk of stroke with sub clinical AF is lower than for clinical AF , and very few patients with sub clinical AF alone have been included in large AF anticoagulation trials . The net benefit of anticoagulation in patients with sub clinical AF is unknown . Design ARTESiA is a prospect i ve , multicenter , double‐blind , r and omized controlled trial , recruiting patients with sub clinical AF detected by an implanted pacemaker , defibrillator , or cardiac monitor , and who have additional risk factors for stroke . Patients with clinical AF documented by surface electrocardiogram will be excluded from the study . Participants will be r and omized to receive either apixaban ( according to st and ard AF dosing ) or aspirin 81 mg daily . The primary outcome is the composite of stroke , transient ischemic attack with diffusion‐weighted magnetic resonance imaging evidence of cerebral infa rct ion , and systemic embolism . Approximately 4,000 patients will be enrolled from around 230 clinical sites , with an anticipated mean follow‐up of 36 months until 248 adjudicated primary outcome events have occurred . Summary ARTESiA will determine whether oral anticoagulation therapy with apixaban compared with aspirin reduces the risk of stroke or systemic embolism in patients with sub clinical AF and additional risk factors The risk for ischemic stroke in patients with atrial fibrillation is related to underlying structural heart disease [ 1 - 3 ] . Although most strokes are believed to arise from embolism of left atrial thrombi [ 4 , 5 ] , other mechanisms may contribute . Transesophageal echocardiography ( TEE ) provides a unique diagnostic window for evaluating the left atrium , left atrial appendage , and thoracic aorta , but the manner in which specific TEE findings in patients with atrial fibrillation correlate with thromboembolic risk and response to therapy has not been fully established [ 6 - 13 ] . We performed TEE in patients with nonvalvular atrial fibrillation who were at high intrinsic risk for thromboembolism and were participating in the Stroke Prevention in Atrial Fibrillation ( SPAF-III ) study , a r and omized clinical trial . In that study , adjusted-dose warfarin ( target international normalized ratio [ INR ] , 2 to 3 ) was compared with combination therapy consisting of low-intensity warfarin ( INR , 1.2 to 1.5 ) plus aspirin , 325 mg/d . The trial was stopped after an interim analysis indicated that the efficacy of adjusted-dose warfarin therapy was superior to that of combination therapy . Low anticoagulation intensity in the combination therapy group yielded high stroke rates that were similar to those expected during treatment with aspirin alone [ 14 , 15 ] . In the current analysis , we 1 ) correlate TEE observations among patients with atrial fibrillation at high risk for thromboembolism with rate of subsequent stroke and 2 ) compare treatment responses . Methods Patients Patients were recruited from the SPAF-III multicenter trial , which was design ed to compare two antithrombotic medication regimens for prevention of ischemic stroke and systemic embolism ( primary events ) . The study , whose design is described else-where in detail [ 14 ] , involved patients with nonvalvular atrial fibrillation who were stratified for risk on the basis of clinical and transthoracic echocardiographic criteria derived from previous analyses [ 15 ] . Women older than 75 years of age and patients of any age and either sex with systolic hypertension ( systolic blood pressure > 160 mm Hg ) , previous thromboembolism , or impaired left ventricular function ( M-mode echocardiographic fractional shortening of 0.25 or recent clinical congestive heart failure ) were r and omly assigned to receive adjusted-dose warfarin ( target INR , 2.0 to 3.0 ) or a combination of low-intensity warfarin ( 0.5 to 3.0 mg/d ; dose was initially adjusted to cause deviation of the INR to 1.2 to 1.5 and was then fixed ) and aspirin . Seventy-three percent of the patients were receiving warfarin at various dose intensities before trial entry ; these patients were equally distributed between assigned treatment groups . Antithrombotic treatment was assigned before performance of TEE and was not influenced by TEE findings . Patients were followed monthly by telephone and in clinic every 3 months , and a st and ard question naire on stroke symptoms was administered annually . All patients whose responses to the question naire suggested the occurrence of stroke were referred for clinical examination by a local affiliated neurologist who was blinded to treatment , and all events were adjudicated by a blinded event verification committee [ 14 ] . This project was design ed to supplement the SPAF-III clinical trial on the basis of the hypothesis that spontaneous echocardiographic contrast detected by TEE identifies patients at high risk for thromboembolism for whom adjusted-dose warfarin  would prove superior to  combination therapy . All participants in the parent study were encouraged , but not required , to provide separate , written informed consent for TEE after r and om assignment to antithrombotic treatment . This was done to prevent the results of TEE from influencing recruitment of patients into the trial or from altering treatment . The intended sample size of 412 TEE examinations was selected to detect an absolute difference in event rates of 3.9 % per year ( based on projected event rates of 5.4 % per year in patients with spontaneous echocardiographic contrast and 1.5 % per year in patients without contrast ) over a mean observation period of 2.5 years . Secondary objectives were to correlate clinical thromboembolic events with function of the left atrial appendage , thrombus of the left atrium and left atrial appendage , and atherosclerotic lesions in the thoracic aorta imaged by TEE . Transesophageal Echocardiography Transesophageal echocardiography was performed within 3 months of enrollment with patients under light sedation and topical anesthesia , according to specific protocol s for acquisition and interpretation [ 16 ] . Commercially available ultrasonography equipment incorporated biplane or multiplane transducers with at least 48 crystals operating at a st and ard frequency of 5 MHz with gray-scale imaging . Signal processing , log compression , and persistence values were established for each manufacturer . Images were interpreted locally , and data were entered into st and ardized forms by echocardiographers who were blinded to antithrombotic treatment assignment but not to patient demographic or clinical features . Original videotaped recordings were collected in a central echocardiographic registry for validation and quality control . To assure generalizability of the results to laboratories used in clinical practice , the analyses reported here are based on image interpretation at the local laboratories . The following features were specifically assessed : left atrial appendage size , peak ante grade ( emptying ) velocity of blood flow in the left atrial appendage , spontaneous echocardiographic contrast in the left atrium or left atrial appendage , thrombus of the left atrium or left atrial appendage , and atherosclerotic disease of the thoracic aorta . Spontaneous echocardiographic contrast was defined as a pattern of slowly swirling intracavitary echodensities imaged with gain setting s adjusted to distinguish background noise . Contrast was classified as faint when visualized intermittently during the cardiac cycle or when enhanced gain setting s were required for detection and was classified as dense when continuously present at st and ard gain . Aortic plaque was classified by location and as either simple or complex according to mobility , ulceration , pedunculation , or thickness greater than 4 mm [ 16 ] . We postulated that reduced emptying velocity from the left atrial appendage , which reflects stasis , would be associated with dense spontaneous echocardiographic contrast and thrombus formation , whereas complex aortic plaque would be a consequence of atherosclerotic vascular abnormality . We also postulated that these findings would predispose patients to ischemic stroke through separate pathogenic mechanisms . Statistical Analysis The analyses reported here were limited to variables accessible only by TEE and were hypothesized a priori to have potential predictive relations to clinical thromboembolism . Baseline comparisons between groups were done by using the chi-square test for categorical data and the Student t-test for continuous variables . The Cox proportional-hazards regression model was used to estimate the univariate relative risk associated with TEE characteristics . The primary analysis compared rates of cerebral ischemic events and systemic embolism among patients who had dense spontaneous echocardiographic contrast detected in the left atrium or left atrial appendage with rates in patients who did not have dense contrast ; the log-rank statistic was used to compare the times to events between these groups . Secondary analyses , conducted similarly , compared event rates in groups that were identified by left atrial appendage size , flow velocity , thrombus , and aortic plaque . For these comparisons , the area of the left atrial appendage was dichotomized at the upper quartile ; flow velocity was dichotomized at the lower quartile . When interaction was seen between treatment and TEE characteristics , analysis of the relation of TEE findings to events was confined to the combination therapy group and treatment effect was described separately ; when no interaction was seen , the analysis was stratified by therapy . The relative reduction in event rate associated with adjusted-dose warfarin therapy was computed as the difference between unity and the rate ratio determined by a Poisson regression model [ 17 ] . A Cox proportional-hazards regression model was fit to confirm the independence of TEE characteristics identified as univariate thromboembolic risk factors . Confidence intervals for event rates were calculated by using a Poisson regression model ; tests of significance were two-sided and were not adjusted for multiple comparisons . All analyses were done according to the intention-to-treat principle . Results Of 1044 high-risk patients with atrial fibrillation enrolled in the r and omized trial , 382 ( 37 % ) volunteered for TEE ( range , 10 % to 80 % of SPAF-III participants recruited at 18 clinical centers offering TEE ) . Salient features of these 382 patients were similar to those of the 662 participants who did not undergo transesophageal imaging ( Table 1 ) . The mean patient age was 71 years , 36 % of patients had clinical ischemic heart disease , and almost half had a history of congestive heart failure . Balanced proportions of patients were assigned to therapy with adjusted-dose warfarin ( n = 190 ) or fixed-dose warfarin and aspirin ( n = 192 ) . Time from r and om assignment of treatment to TEE was similar in the two groups ( mean , 23 days ) . The trial was stopped after a mean observation period of 1.1 years because an interim analysis indicated the lack of efficacy of the combination regimen [ 18 ] . Up to that point , 23 primary events ( all of which were ischemic strokes ) occurred in the subset of participants who had undergone TEE ( event rate , 3.1 % per year in patients assigned to adjusted-dose warfarin compared with 7.8 % per year in those assigned to combination therapy ; P = 0.04 ) . BACKGROUND Atrial fibrillation ( AF ) is the most common sustained cardiac arrhythmia and it is associated with an increased stroke risk , due mainly to cardiac embolism from the left atrial appendage ( LAA ) . Percutaneous LAA closure is a method to reduce stroke risk in AF without using anticoagulant agents . In this study we report data from an Italian experience with the LAA occluder Amplatzer Cardiac Plug ( ACP ) device ( Aga Medical Corporation , Plymouth , MN , USA ) . METHODS The study was design ed to evaluate the safety of LAA closure using ACP and the efficacy of the procedure in preventing strokes during a 1-year follow-up . Patients with permanent or paroxysmal AF , high stroke risk , and contraindication to warfarin therapy were selected for the procedure . RESULTS The LAA closure was attempted in 37 patients and succeeded in 34 cases ( 91.9 % ) . Four patients experienced serious complications ( one cardiac tamponade requiring pericardiocentesis , two device embolizations , one low-rate response AF requiring artificial pacing ) . During a 1-year follow-up , ischemic stroke occurred in one of 34 patients , result ing in a stroke rate of 2.94 % ; thus there was a stroke rate reduction of 50.2 % and 26.5 % compared to the expected stroke rate , according to CHADS2 and CHA2 DS2 VASc score . None of the patients who received ACP experienced major bleeding during the follow-up . CONCLUSION LAA closure using ACP is a relatively feasible procedure which can be performed by highly experienced operators to reduce stroke rate in patients with AF , high stroke risk , and contraindication to oral anticoagulants BACKGROUND Atrial fibrillation ( AF ) is a common arrhythmia and a major risk factor for stroke . Many physicians remain reluctant to provide stroke prevention by anticoagulant therapy especially for elderly individuals with AF . Using multivariate regression analyses , we studied the characteristics and the prognosis of stroke in patients with AF . METHODS The study is part of the Copenhagen Stroke Study , a prospect i ve , community-based study of 1197 patients with acute stroke treated on a stroke unit from the time of acute admission to the end of rehabilitation .  Initial stroke severity was measured by the Sc and inavian Neurological Stroke Scale ( SSS ) . Neurological and functional outcomes were evaluated by the SSS and the Barthel Index . RESULTS AF was diagnosed in 18 % of the patients . AF increased steeply with age in the stroke population , from 2 % in patients < 50 years old , 15 % in patients in their 70s , and 28 % in patients in their 80s , to 40 % in patients > or = 90 years of age . In a multivariate analysis AF was associated with age ( odds ratio [ OR ] , 2.0 per 10-year increase ; 95 % confidence ratio [ CI ] , 1.6 to 2.6 ) , ischemic heart disease ( OR , 3.4 ; 95 % CI , 2.4 to 4.8 ) , previous stroke ( OR , 1.8 ; 95 % CI , 1.2 to 2.6 ) , and systolic blood pressure ( OR , 0.93 per 10-mm Hg increases ; 95 % CI , 0.88 to 0.99 ) , but not with sex , diabetes , hypertension , previous transient ischemic attack , or silent infa rct ion on computed tomography . Patients with AF had a higher mortality rate ( OR , 1.7 ; 95 % CI , 1.2 to 2.5 ) , longer hospital stays ( 50 days versus 40 days , P < .001 ) , and a lower discharge rate to their own homes ( OR , 0.60 ; 95 % CI , 0.44 to 0.85 ) . Neurological and functional outcomes were markedly poorer in patients with AF . Poorer outcome was exclusively explained by initially more-severe strokes . CONCLUSIONS Stroke in patients with AF is generally more severe and outcome markedly poorer than in patients with sinus rhythm . This accentuates the importance of anticoagulant treatment of individuals with AF . A lower blood pressure in the acute stage of stroke may contribute to the increased stroke severity in patients with AF Background Patients with atrial fibrillation ( AF ) are prone to cardiovascular events and anticoagulation‐related bleeding complications . We hypothesized that patients with anemia are at increased risk for these outcomes . Methods We performed a post hoc analysis of the ARISTOTLE trial , which included > 18,000 patients with AF r and omized to warfarin ( target international normalized ratio , 2.0‐3.0 ) or apixaban 5 mg twice daily .  Multivariable Cox regression analysis was used to determine if anemia ( defined as hemoglobin < 13.0 in men and < 12.0 g/dL in women ) was associated with future stroke , major bleeding , or mortality . Results Anemia was present at baseline in 12.6 % of the ARISTOTLE population . Patients with anemia were older , had higher mean CHADS2 and HAS‐BLED scores , and were more likely to have experienced previous bleeding events . Anemia was associated with major bleeding ( adjusted hazard ratio [ HR ] , 1.92 ; 95 % CI , 1.62‐2.28 ; P < .0001 ) and all‐cause mortality ( adjusted HR , 1.68 ; 95 % CI , 1.46‐1.93 ; P < .0001 ) but not stroke or systemic embolism ( adjusted HR , 0.92 ; 95 % CI , 0.70‐1.21 ) . The benefits of apixaban compared with warfarin  on the rates of stroke , mortality , and bleeding events were consistent in patients with and without anemia . Conclusions Chronic anemia is associated with a higher incidence of bleeding complications and mortality , but not of stroke , in anticoagulated patients with AF .  Apixaban is an attractive anticoagulant for stroke prevention in patients with AF with or without anemia A number of r and omized controlled trials in atrial fibrillation ( AF ) conducted in the last century showed that vitamin K antagonists , ( VKAs ) , principally warfarin , were remarkably effective in stroke prevention , reducing stroke by 64 % and all-cause mortality by 26 % , figures rarely matched in treatments of other diseases . With the introduction of the non-VKA anticoagulants ( NOACs ) in the last 8 years , stroke reduction in the r and omized trials was similar to VKAs , but with less intracranial haemorrhage and a further 1 % absolute risk reduction in total mortality ; results confirmed in many ‘ real-life ’ studies using administrative or registry data . Many guidelines , including the first joint AHA/ACC/ESC guideline in 2001 , recommended oral anticoagulant ( OAC ) therapy for those with AF at elevated risk of stroke , as have subsequent joint and ESC guidelines and up date s in 2006 , 2010 , 2012 , and 2016 . But OAC uptake has been less than ideal for some time , hovering in the UK at 50 % of those for whom OAC was guideline recommended , in the 10 years from 2001 to 2011 . The data from the Swedish RIKS registry of > 94 000 strokes help identify the two major gaps in prevention of AF-related strokes , which represent 33 % of all ischaemic strokes ( Take home figure ) . In 9 % of all strokes , AF was not known prior to stroke : prevention would require screening to detect and treat unknown AF . In another 20 % , AF was known but patients were either on no antithrombotic therapy ( 8 % ) or on antiplatelet therapy alone ( 12 % ) , which is largely ineffective for AF thrombo-prophylaxis . Thus , up to 20 % of ischaemic strokes might be prevented if the evidence – practice gap of OAC prescription was eliminated . It is therefore very pleasing to see in this issue of the European Heart Journal that in the UK ,  OAC use in patients with elevated stroke risk  has increased from < 50 % to almost 80 % in the 10 years from 2006 to 2016 , mostly in the latter 5 years , while  antiplatelet therapy  has reduced from 43 % to 16 % . This is a great success story , observed to some degree in many countries , but by no means uniformly , even within the same country . Trying to pinpoint the reason for this improvement is not easy . Success has many fathers , while failure is an orphan . Cowan and colleagues postulate that successive ESC and NICE guidelines , quality improvement incentivization programmes such as GRASP and QOF , or licensing and marketing of NOACs , accentuating their ease of use , could all have played a role , but it is difficult to determine which is the major one . ESC guidelines and their up date s were recommending OAC in 2001 , 2006 , and 2010 , and the GRASP quality initiative from 2009 , with little change in OAC uptake , while QOF did not commence until 2012 . It is instructive to look at our own UK data using a higher resolution temporal trend of OAC initiation within 90 days of incident AF ( Figure 1 ) . The graph plots total OAC initiations for patients with CHA2DS2-VASc > _ 2 . A rise in VKA OAC prescription was observed from early 2011 , when limited marketing preceded the availability of NOAC drugs , followed by an accentuated increase due to NOAC prescription accompanied by a plateau in VKA prescription . It is quite likely that at this time point , the availability and marketing of NOACs played a dominant role , with this influence increasing as additional NOACs became available . The final increase from 2013 to 2106 is probably a combination of all three factors : an effective national QOF quality framework , gradual percolation of guidelines and up date s , and continued marketing of NOACs . Ensuring that a high proportion of patients with AF are taking effective doses of OAC rather than aspirin requires first that OAC is offered by the physician and accepted by the patient , secondly that patients are adherent to taking the drugs as prescribed , achieving > 70 % time in the therapeutic international normalized ratio ( INR ) range for VKAs , and finally , that patients persist with taking  OAC therapy long-term . There is a high non-persistence rate for OAC in the first 2 years after initiation , significantly greater for VKAs than INTRODUCTION Atrial fibrillation ( AF ) is an important independent risk factor for stroke and oral anticoagulation therapy provides a highly effective treatment to reduce this risk . Active screening strategies improve detection of AF in comparison with routine care ; however , whether screen-detected patients have stroke risk profiles favouring anticoagulation is unclear . Using data derived from the screening for AF in the elderly ( SAFE ) study , the aim of this article was to determine if patients with AF detected via active screening  have stroke risk profiles that warrant prophylactic anticoagulation . METHODS Secondary analysis of data derived from 25 general practice s within which cohorts of 200 patients were r and omly allocated to opportunistic [ pulse and electrocardiogram ( ECG ) ] or systematic screening ( postal invitation for ECG ) .  Stroke risk assessment was undertaken using baseline data extracted from medical records and CHADS2 criteria . CHADS2 scores were compared between the screening groups . RESULTS One hundred and forty-nine new cases of AF were detected , 75 via opportunistic screening and 74 via systematic screening . CHADS2 scores were ≥1 in 83 % [ 95 % confidence interval ( CI ) 72.6 - 89.6 ] of patients detected via opportunistic screening and 78 % ( 95 % CI 67.7 - 86.2 ) detected via systematic screening . There were no significant differences in stroke risk profiles of patients detected via opportunistic and systematic screenings . CONCLUSION Stroke risk profiles of patients detected via opportunistic and systematic screenings were similar . Data derived from the SAFE study suggest that active screening for AF in patients aged ≥65 years in primary care is a useful screening programme with 78 - 83 % of patients identified eligible for anticoagulation treatment according to the CHADS2 criteria AIMS Atrial fibrillation patients with prior embolism have a high risk of vascular events in spite of anticoagulant therapy and elderly patients carry an additional risk . We analysed and compared vascular events-rate between older and younger than 75 years atrial fibrillation patients r and omized to anticoagulant-alone or combined antiplatelet plus moderate-level anticoagulant therapy . METHODS AND RESULTS A total of 967 patients stratified by age and the history of prior embolism were r and omized to therapeutic doses of anticoagulant-alone or combined antithrombotic therapy . Primary events were fatal and non-fatal ischaemic or haemorrhagic stroke/transient ischaemic attack , systemic embolism and myocardial infa rct ion , sudden death and death from bleeding . The elderly , compared with the younger patients , had higher event-rate [ hazard ratio 2.31 ( 95 % confidence interval 1.37 - 3.90 ) , P < 0.003 ] . The elderly suffered higher severe bleeding event-rate during anticoagulant therapy . The combined , compared with the anticoagulant therapy , reduced the vascular events-rate in the elderly ( P = 0.012 ) and caused less intracranial haemorrhages and less bleeding mortality , although more non-fatal gastric bleeding . CONCLUSION The elderly with AF had a higher event-rate than the younger patients . A higher severe bleeding event-rate was also registered in elderly patients receiving anticoagulant therapy .  Combined , compared with anticoagulant therapy , significantly reduced vascular events and bleeding mortality in elderly patients BACKGROUND A combination of low-dose aspirin ( A ) and anticoagulation ( AC ) may provide better protection against thromboembolic events compared with AC alone in high-risk patients with atrial fibrillation ( AF ) . METHODS We performed a multicentric placebo-controlled double blind-trial to test the preventive efficacy against thromboembolic events of the addition of aspirin ( A ) ( 100 mg ) or placebo ( P ) to anticoagulant treatment in patients with high-risk atrial fibrillation . A total of 157 patients were included , with atrial fibrillation and previous thromboembolic event or older than 65 years with either a history of hypertension , a recent episode of heart failure or a left ventricular dysfunction . All patients received fluindione ( F ) and P or F and A , with an INR target between 2 and 2.6 . The primary endpoint was a combined endpoint of stroke ( ischaemic or haemorrhagic ) , myocardial infa rct ion , systemic arterial emboli or vascular death . RESULTS The study had to be stopped prematurely owing to a too low recruitment rate . During follow-up ( 0.84 years ) 3 non-fatal thromboembolic events were recorded ( 1P , 2A ) and 6 patients died ( 3P , 3A ) , none of them from a thromboembolic complication . However , 3 deaths were secondary to severe haemorrhagic complications ( 1P , 2A ) . Non-fatal haemorrhagic complications occurred more often in group A ( n = 10 , 13.1 pour cent ) compared with group P ( n = 1 , 1.2 pour cent ) , p = 0.003 . CONCLUSION The FFAACS study was not able to show any therapeutic benefit from the addition of aspirin to anticoagulant in patients with high-risk AF . Such a combination increased the incidence rate of bleeding complications , which therefore greatly reduces its potential overall benefit Background and Purpose — Stroke risk increases with age in patients who have nonvalvular atrial fibrillation . It is uncertain whether the efficacy of stroke prevention therapies in atrial fibrillation changes as patients age . The objective of this study was to determine the effect of age on the relative efficacy of oral anticoagulants ( OAC ) and antiplatelet ( AP ) therapy ( including acetylsalicylic acid and triflusal ) on ischemic stroke , serious bleeding , and vascular events in patients with atrial fibrillation . Methods — This is an analysis of the Atrial Fibrillation Investigators data base , which contains patient level- data from r and omized trials of stroke prevention in atrial fibrillation . We used Cox regression models with age as a continuous variable that controlled for sex , year of r and omization , and history of cerebrovascular disease , diabetes , hypertension , and congestive heart failure . Outcomes included ischemic stroke , serious bleeding ( intracranial hemorrhage or systemic bleeding requiring hospitalization , transfusion , or surgery ) , and cardiovascular events ( ischemic stroke , myocardial infa rct ion , systemic embolism , or vascular death ) . Results — The analysis included 8932 patients and 17 685 years of observation from 12 trials . Patient age increased risk of ischemic stroke ( adjusted hazard ratio per decade increase 1.45 ; 95 % CI , 1.26 to 1.66 ) , serious bleeding ( 1.61 ; 1.47 to 1.77 ) , and cardiovascular events ( 1.43 ; 1.33 to 1.53 ) . Compared with placebo , OAC and AP significantly reduced the risk of ischemic stroke ( OAC , 0.36 ; 0.29 to 0.45 ; AP , 0.81 ; 0.72 to 0.90 ) and cardiovascular outcomes ( OAC , 0.59 ; 0.52 to 0.66 ; AP , 0.81 ; 0.75 to 0.88 ) , whereas OAC increased risk of serious bleeding ( 1.56 ; 1.03 to 2.37 ) . The relative benefit of OAC versus placebo or AP did not vary by patient age for any outcome . Compared with placebo , the relative benefit of AP  for preventing ischemic stroke decreased significantly as patients aged ( P=0.01 ) . Conclusions — As patients with atrial fibrillation age , the relative efficacy of AP to prevent ischemic stroke appears to decrease , whereas it does not change for OAC . Because stroke risk increases with age , the absolute benefit of OAC increases as patients get older
Some of the risk factors for anticoagulation-related bleeding are also indications for the use of anticoagulants in AF patients .
Atrial fibrillation ( AF ) is associated with an increased stroke risk that may be reduced by therapeutic anticoagulation .
However , anticoagulation is associated with an increased risk of bleeding that in some patients may outweigh the benefits in reducing the risk of stroke .