Factors associated with ischemic stroke during aspirin therapy in atrial fibrillation: analysis of 2012 participants in the SPAF I-III clinical trials. The Stroke Prevention in Atrial Fibrillation (SPAF) Investigators. Increased risk of first-ever stroke in younger patients with atrial fibrillation not recommended for antithrombotic therapy by current guidelines: a population-based study in an East Asian cohort of 22 million people. Tissue Doppler index, E/E', and ischemic stroke in patients with atrial fibrillation and preserved left ventricular ejection fraction Hyperuricemia and the risk of ischemic stroke in patients with atrial fibrillation--could it refine clinical risk stratification in AF? Prevalence of atrial fibrillation and eligibility for anticoagulants in the community Is screening for AF worthwhile? Stroke risk in a screened population from the SAFE study. Cost-Effectiveness of Dabigatran for Stroke Prophylaxis in Atrial Fibrillation A randomised controlled trial and cost effectiveness study of systematic screening (targeted and total population screening) versus routine practice for the detection of atrial fibrillation in the over 65s: (SAFE) [ISRCTN19633732] Evaluation of risk stratification schemes for ischaemic stroke and bleeding in 182 678 patients with atrial fibrillation: the Swedish Atrial Fibrillation cohort study. Focused 2012 update of the Canadian Cardiovascular Society atrial fibrillation guidelines: recommendations for stroke prevention and rate/rhythm control. The ORBIT bleeding score: a simple bedside score to assess bleeding risk in atrial fibrillation Stroke due to atrial fibrillation in a population-based stroke registry (Ludwigshafen Stroke Study) CHADS(2) , CHA(2) DS(2) -VASc score, underuse of oral anticoagulation, and implications for preventive measures. Predictors of thromboembolism in atrial fibrillation: II. Echocardiographic features of patients at risk. The Stroke Prevention in Atrial Fibrillation Investigators. Epidemiology of ischemic stroke from atrial fibrillation in Dijon, France, from 1985 to 2006 Atrial Fibrillation Is a Major Risk Factor for Stroke, Especially in Women: The Jichi Medical School Cohort Study Stroke with intermittent atrial fibrillation: incidence and predictors during aspirin therapy. Stroke Prevention in Atrial Fibrillation Investigators. Comparative validation of a novel risk score for predicting bleeding risk in anticoagulated patients with atrial fibrillation: the HAS-BLED (Hypertension, Abnormal Renal/Liver Function, Stroke, Bleeding History or Predisposition, Labile INR, Elderly, Drugs/Alcohol Concomitantly) score. Gender Differences in the Risk of Ischemic Stroke and Peripheral Embolism in Atrial Fibrillation: The AnTicoagulation and Risk factors In Atrial fibrillation (ATRIA) Study Screening for atrial fibrillation in the community: a multicenter validation trial. The Relationship Between Daily Atrial Tachyarrhythmia Burden From Implantable Device Diagnostics and Stroke Risk: The TRENDS Study Cardioembolic vs. Noncardioembolic Strokes in Atrial Fibrillation: Frequency and Effect of Antithrombotic Agents in the Stroke Prevention in Atrial Fibrillation Studies A risk score for predicting stroke or death in individuals with new-onset atrial fibrillation in the community: the Framingham Heart Study. Impact of vascular disease in predicting stroke and death in patients with atrial fibrillation: the Danish Diet, Cancer and Health cohort study.
BACKGROUND AND PURPOSE Nonvalvular atrial fibrillation ( AF ) is a strong , independent risk factor for stroke , but the absolute rate of stroke varies widely among AF patients , importantly influencing the potential benefit of antithrombotic prophylaxis . We explore factors associated with ischemic stroke in AF patients taking aspirin .  METHODS We performed multivariate logistic regression analysis of 2012 participants given aspirin alone or in combination with low , inefficacious doses of warfarin in the Stroke Prevention in Atrial Fibrillation I-III trials followed for a mean of 2.0 years , during which 130 ischemic strokes were observed . RESULTS Age ( relative risk [RR]=1.8 per decade , P<0.001 ) , female sex ( RR=1.6 , P=0.01 ) , history of hypertension ( RR=2.0 , P<0.001 ) , systolic blood pressure > 160 mm Hg ( RR=2.3 , P<0.001 ) , and prior stroke or transient ischemic attack ( RR=2.9 , P<0.001 ) were independently associated with increased stroke risk . Regular consumption of > /=14 alcohol-containing drinks per week was associated with reduced stroke risk ( adjusted RR=0.4 , P=0.04 ) . Among SPAF III participants , estrogen hormone replacement therapy was associated with a higher risk of ischemic stroke ( adjusted RR=3.2 , P=0.007 ) . With the use of these variables , a risk stratification scheme for primary prevention separated participants into those with high ( 7.1%/y , 22 % of the cohort ) , moderate ( 2.6%/y , 37 % of the cohort ) , and low ( 0.9%/y , 41 % of the cohort ) rates of stroke . Ischemic strokes in low-risk participants were less often disabling ( P<0.001 ) . CONCLUSIONS Patients with AF who have high and low rates of stroke during treatment with  aspirin can be identified . However , validation of our risk stratification scheme is necessary before it can be applied with confidence to clinical management . Postmenopausal estrogen replacement therapy and moderate alcohol consumption may additionally modify the risk of stroke in AF , but these findings require confirmation OBJECTIVE To assess the risk of first-ever ischemic stroke in younger patients with atrial fibrillation ( AF ) who have none of the CHA2DS2-VASc ( congestive heart failure , hypertension , age ≥75 years , diabetes mellitus , previous stroke/transient ischemic attack , vascular disease , age 65 - 74 years , sex category [ female sex ] ) risk factors ( excluding female sex ) by using the National Health Insurance research data base in Taiwan . PATIENTS AND METHODS From 22,842,778 insured people , we identified 24,612 hospitalized patients with newly diagnosed AF between January 1 , 2002 , and December 31 , 2004 , as the AF group and r and omly selected 98,448 age- and sex-matched persons without AF as the non-AF group . Both groups were followed up until December 31 , 2010 , to estimate ischemic stroke incidences in relation to other stroke risk factors . RESULTS During a follow-up period of 89,468 person-years , the stroke rate was higher in patients with AF than in those without AF ( 5.79 per 100 person-years vs 2.25 per 100 person-years ) . The higher prevalence of CHA2DS2-VASc comorbidities ( heart failure , hypertension , diabetes , coronary artery disease , and peripheral artery disease ) in patients with AF further increased the stroke risk . In 790 patients with AF aged 30 to 55 years who had none of the CHA2DS2-VASc comorbidities at baseline and retained a " low risk , " that is , those with a CHA2DS2-VASc score of 0 in men and 1 in women during follow-up , the stroke rate remained considerably higher than that in their non-AF counterparts ( 1.00 per 100 person-years vs 0.25 per 100 person-years ) , with a sex-adjusted hazard ratio of 4.09 ( 95 % CI , 2.97 - 5.62 ) . CONCLUSION This study finds an increased risk of stroke in younger patients with AF who are not recommended for prevention of thromboembolism by current guidelines . Better stroke risk stratification tools are needed to prioritize younger patients with AF for thromboprophylactic therapy in this population BACKGROUND Although several risk factors for stroke have been reported in patients with atrial fibrillation ( AF ) , the relation of LV diastolic dysfunction to stroke is still uncertain in these patients . We evaluated the relationship between tissue Doppler-derived index , E/E ' , as well as other clinical and echocardiographic parameters and ischemic stroke by this cross-sectional study . METHODS Three hundred thirty patients with persistent AF who had preserved LV ejection fraction were included from 6 centers . Clinical data were obtained and st and ard transthoracic echocardiography was performed . Patients without a history of ischemic stroke ( n=280 ) were compared with patients with this complication ( n=50 ) . Potential determinants of ischemic stroke were identified by logistic regression analyses . RESULTS In univariate analyses , age , history of hypertension , diabetes mellitus , hyperlipidemia and symptomatic heart failure , plasma brain natriuretic peptide ( BNP ) level , early mitral inflow velocity ( E ) , diastolic mitral annular velocity ( E ' ) , and E/E ' ratio were significantly correlated to ischemic stroke . Multivariate regression analyses identified two significant variables that were independently associated with ischemic stroke : hypertension ( odds ratio=6.03 , p=0.008 ) , and E/E ' ( odds ratio=1.21 , p=0.002 ) . CONCLUSIONS These findings may have clinical implication s that LV diastolic dysfunction , reflected by E/E ' , is a significant determinant of ischemic stroke in AF . A larger prospect i ve data is needed to confirm the value of E/E ' in risk stratification for ischemic stroke in this population BACKGROUND Although hyperuricemia has been reported to be a risk factor of stroke , the relationship between hyperuricemia and stroke in patients with atrial fibrillation ( AF ) remains uncertain . The goal of the present study was to investigate whether hyperuricemia could potentially refine clinical risk stratification in AF . METHODS This study used the " National Health Insurance Research Data base " in Taiwan . A total of 7601 AF patients who did not receive antiplatelet agents or oral anticoagulants were identified as the study population . Hyperuricemia was defined as having at least one episode of gout attack necessitating long-term treatment with uric acid-lowering agents . The association between hyperuricemia and ischemic stroke was analyzed . RESULTS During the follow up of 3.0±2.7 years , 1116 patients ( 14.7 % ) experienced ischemic stroke with an annual rate of around 4.9 % . Hyperuricemia significantly predicts stroke , with a hazard ratio ( HR ) of 1.280 after adjusting for CHA2DS2-VASc score and other comorbidities . Among the 376 patients with a CHA2DS2VASc score of 0 , hyperuricemia can further stratify them into 2 groups with different stroke rates ( 7.1 % versus 1.3 % , p=0.020 ) . The adjusted HR of hyperuricemia in predicting ischemic stroke diminished from 7.491 for patients with a CHA2DS2-VASc score of 0 to 1.659 for those with a score of 3 , and became insignificant for patients with a score ≥4 . CONCLUSIONS Hyperuricemia was a significant risk factor of stroke which could potentially refine the clinical risk stratification in AF . It deserves a prospect i ve trial to investigate whether it would change the current strategy for stroke preventions using oral anticoagulants 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 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 Background — Recent studies have investigated alternatives to warfarin for stroke prophylaxis in patients with atrial fibrillation ( AF ) , but whether these alternatives are cost-effective is unknown . Methods and Results — On the basis of the results from R and omized Evaluation of Long Term Anticoagulation Therapy ( RE-LY ) and other trials , we developed a decision- analysis model to compare the cost and quality -adjusted survival of various antithrombotic therapies . We ran our Markov model in a hypothetical cohort of 70-year-old patients with AF using a cost-effectiveness threshold of $ 50 000/ quality -adjusted life-year . We estimated the cost of dabigatran as US $ 9 a day . For a patient with an average risk of major hemorrhage ( ≈3%/y ) , the most cost-effective therapy depended on stroke risk . For patients with the lowest stroke rate ( CHADS2 stroke score of 0 ) , only aspirin was cost-effective . For patients with a moderate stroke rate ( CHADS2 score of 1 or 2 ) , warfarin was cost-effective unless the risk of hemorrhage was high or quality of international normalized ratio control was poor ( time in the therapeutic range < 57.1 % ) . For patients with a high stroke risk ( CHADS2 stroke score ≥3 ) , dabigatran 150 mg ( twice daily ) was cost-effective unless international normalized ratio control was excellent ( time in the therapeutic range > 72.6 % ) . Neither dabigatran 110 mg nor dual therapy ( aspirin and clopidogrel ) was cost-effective . Conclusions — Dabigatran 150 mg ( twice daily ) was cost-effective in AF population s at high risk of hemorrhage or high risk of stroke unless international normalized ratio control with warfarin was excellent . Warfarin was cost-effective in moderate-risk AF population s unless international normalized ratio control was poor Background Atrial fibrillation ( AF ) has been recognised as an important independent risk factor for thromboembolic disease , particularly stroke for which it provides a five-fold increase in risk . This study aim ed to determine the baseline prevalence and the incidence of AF based on a variety of screening strategies and in doing so to evaluate the incremental cost-effectiveness of different screening strategies , including targeted or whole population screening , compared with routine clinical practice , for detection of AF in people aged 65 and over . The value of clinical assessment and echocardiography as additional methods of risk stratification for thromboembolic disease in patients with AF were also evaluated . Methods The study design was a multi-centre r and omised controlled trial with a study population of patients aged 65 and over from 50 General Practice s in the West Midl and s. These purpose fully selected general practice s were r and omly allocated to 25 intervention practice s and 25 control practice s. GPs and practice nurses within the intervention practice s received education on the importance of AF detection and ECG interpretation . Patients in the intervention practice s were r and omly allocated to systematic ( n = 5000 ) or opportunistic screening ( n = 5000 ) . Prospect i ve identification of pre-existing risk factors for AF within the screened population enabled comparison between high risk targeted screening and total population screening . AF detection rates in systematic ally screened and opportunistically screened population s in the intervention practice s were compared to AF detection rate in 5,000 patients in the control practice AIMS The impact of some risk factors for stroke and bleeding , and the value of stroke and bleeding risk scores , in atrial fibrillation ( AF ) , has been debated , as clinical trial cohorts have not adequately tested these . Our objective was to investigate risk factors for stroke and bleeding in AF , and application of the new CHA(2)DS(2)-VASc and HAS-BLED schemes for stroke and bleeding risk assessment s , respectively . METHODS AND RESULTS We used the Swedish Atrial Fibrillation cohort study , a nationwide cohort study of 182 678 subjects with a diagnosis of AF at any Swedish hospital between 1 July 2005 and 31 December 2008 , who were prospect ively followed for an average of 1.5 years ( 260 000 years at risk ) . With the use of the National Swedish Drug Registry , all patients who used an oral anticoagulant  anytime during follow-up were identified . Most of the analyses were made on a subset of 90 490 patients who never used anticoagulants .  Risk factors for stroke , the composite thromboembolism endpoint ( stroke , TIA , or systemic embolism ) , and bleeding , and the performance of published stroke and bleeding risk stratification schemes were investigated . On multivariable analysis , significant associations were found between the following ' new ' risk factors and thromboembolic events ; peripheral artery disease [ hazard ratio ( HR ) 1.22 ( 95 % CI 1.12 - 1.32 ) ] , ' vascular disease ' [ HR 1.14 ( 1.06 - 1.23 ) ] , prior myocardial infa rct ion [ HR 1.09 ( 1.03 - 1.15 ) ] , and female gender [ HR 1.17 ( 1.11 - 1.22 ) ] . Previous embolic events , intracranial haemorrhage ( ICH ) , hypertension , diabetes , and renal failure were other independent predictors of the composite thromboembolism endpoint , while thyroid disease ( or hyperthyroidism ) was not an independent stroke risk factor . C-statistics for the composite thromboembolic endpoint with the CHADS(2 ) and CHA(2)DS(2)-VASc schemes were 0.66 ( 0.65 - 0.66 ) and 0.67 ( 0.67 - 0.68 ) , respectively . On multivariable analysis , age , prior ischaemic stroke or thromboembolism , prior major bleeding events , and hypertension were significant predictors of ICH and major bleeding . Heart failure , diabetes , renal failure , liver disease , anaemia or platelet/coagulation defect , alcohol abuse , and cancer were other significant predictors for major bleeding , but not ICH . The ability for predicting ICH and major bleeding with both bleeding risk schemes ( HEMORR(2)HAGES , HAS-BLED ) were similar , with c-statistics of ~0.6 . CONCLUSION Several independent risk factors ( prior ICH , myocardial infa rct ion , vascular disease , and renal failure ) predict ischaemic stroke and /or the composite thromboembolism endpoint in AF , but thyroid disease ( or hyperthyroidism ) was not an independent risk factor for stroke . There is a better performance for CHA(2)DS(2)-VASc over CHADS(2 ) schemes for the composite thromboembolism endpoint . While both tested bleeding risk schemes have similar predictive value , the HAS-BLED score has the advantage of simplicity 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 Therapeutic decisions in atrial fibrillation ( AF ) are often influenced by assessment of bleeding risk . However , existing bleeding risk scores have limitations . Objectives We sought to develop and vali date a novel bleeding risk score using routinely available clinical information to predict major bleeding in a large , community-based AF population . Methods We analysed data from Outcomes Registry for Better Informed Treatment of Atrial Fibrillation ( ORBIT-AF ) , a prospect i ve registry that enrolled incident and prevalent AF patients at 176 US sites . Using Cox proportional hazards regression , we identified factors independently associated with major bleeding among patients taking oral anticoagulation ( OAC ) over a median follow-up of 2 years ( interquartile range = 1.6–2.5 ) . We also created a numerical bedside risk score that included the five most predictive risk factors weighted according to their strength of association with major bleeding . The predictive performance of the full model , the simple five-item score , and two existing risk scores ( hypertension , abnormal renal/liver function , stroke , bleeding history or predisposition , labile INR , elderly , drugs/alcohol concomitantly , HAS-BLED , and anticoagulation and risk factors in atrial fibrillation , ATRIA ) were then assessed in both the ORBIT-AF cohort and a separate clinical trial population , Rivaroxaban Once-daily oral direct factor Xa inhibition compared with vitamin K antagonism for prevention of stroke and embolism trial in atrial fibrillation ( ROCKET-AF ) . Results Among 7411 ORBIT-AF patients taking OAC , the rate of major bleeding was 4.0/100 person-years . The full continuous model ( 12 variables ) and five-factor ORBIT risk score ( older age [ 75 + years ] , reduced haemoglobin/haematocrit/history of anaemia , bleeding history , insufficient kidney function , and treatment with antiplatelet ) both had good ability to identify those who bled vs. not ( C-index 0.69 and 0.67 , respectively ) . These scores both had similar discrimination , but markedly better calibration when compared with the HAS-BLED and ATRIA scores in an external validation population from the ROCKET-AF trial . Conclusions The five-element ORBIT bleeding risk score had better ability to predict major bleeding in AF patients when compared with HAS-BLED and ATRIA risk scores . The ORBIT risk score can provide a simple , easily remembered tool to support clinical decision making BACKGROUND AND PURPOSE Atrial fibrillation ( AF ) is amongst the most important etiologies of ischaemic stroke . In a population -based stroke registry , we tested the hypothesis of low adherence to current guidelines as a main cause of high rates of AF-associated stroke . METHODS Within the Ludwigshafen Stroke Study ( LuSSt ) , a prospect i ve ongoing population -based stroke register , we analyzed all patients with a first-ever ischaemic stroke ( FEIS ) owing to AF in 2006 and 2007 . We determined whether AF was diagnosed before stroke and assessed pre-stroke CHADS(2 ) and CHA(2 ) DS(2 ) -VASc scores . RESULTS In total , 187 of 626 patients with FEIS suffered from cardioembolic stroke owing to AF , which was newly diagnosed in 57 ( 31 % ) patients . Retrospective pre-stroke risk stratification according to CHADS(2 ) score indicated low/intermediate risk in 34 patients ( 18 % ) and high risk ( CHADS(2 ) ≥ 2 ) in 153 patients ( 82 % ) . Application of CHA(2 ) DS(2 ) -VASc score reduced number of patients at low/intermediate risk ( CHA(2 ) DS(2 ) -VASc score 0 - 1 ) to five patients ( 2.7 % ) . In patients with a CHADS(2 ) score ≥ 2 and known AF ( n = 106 ) before stroke , 38 ( 36 % ) were on treatment with vitamin K antagonists on admission whilst only in 16 patients ( 15 % ) treatment was in therapeutic range . CONCLUSIONS Our study strongly supports the hypothesis that underuse of oral anticoagulants in high-risk patients importantly contributes to AF-associated stroke . CHA(2 ) DS(2 ) -VASc score appears to be a more valuable risk stratification tool than CHADS(2 ) score . Preventive measures should focus on optimizing pre-stroke detection of AF and better implementation of present AF- guidelines with respect to anticoagulation therapy OBJECTIVE To identify echocardiographic predictors of arterial thromboembolism in patients with nonrheumatic atrial fibrillation and to determine whether these add to clinical variables for risk stratification . DESIGN Cohort study of patients assigned to placebo in a r and omized clinical trial . SETTING Five hundred sixty-eight in patients and out patients with nonrheumatic atrial fibrillation assigned to placebo therapy at 15 U.S. medical centers from 1987 to 1989 in the Stroke Prevention in Atrial Fibrillation study . Patients were followed for a mean of 1.3 years . MEASUREMENTS M-mode and two-dimensional ( 2-D ) echocardiograms performed at study entry and interpreted by local cardiologists . The predictive value of 14 echocardiographic variables for later ischemic stroke or systemic embolism was assessed by multivariate analysis . MAIN RESULTS Left ventricular dysfunction from 2-D echocardiograms ( P = 0.003 ) and the size of the left atrium from M-mode echocardiograms ( P = 0.02 ) were the strongest independent predictors of later thromboembolism . Multivariate analysis of these two independent echocardiographic predictors with the three independent clinical predictors of thromboembolism ( history of hypertension , recent congestive heart failure , previous thromboembolism ) identified 26 % of the cohort with a low risk for thromboembolism ( 1.0 % per year ; 95 % Cl , 0.2 % to 4.0 % ) . Compared with risk stratification using clinical variables alone , echocardiographic results altered thromboembolic risk stratification in 18 % of the entire cohort and in 38 % of those without clinical risk factors . CONCLUSIONS Both left ventricular and left atrial variables are significant predictors of thromboembolism in patients with nonvalvular atrial fibrillation . Our results challenge traditional views of the pathogenesis of ischemic stroke in patients with atrial fibrillation and suggest that st and ard echocardiography contributes to risk stratification , differentiating the one third of patients without clinical risk factors who are at increased risk for stroke from the remainder who may not need antithrombotic prophylaxis Background : Atrial fibrillation ( AF ) is strongly associated with age , and epidemiologic studies are needed to evaluate the impact of both aging of the population and the use of anticoagulant therapy in patients with AF on the incidence of cardioembolic stroke with AF ( CE/AF stroke ) . Methods : We evaluated trends in incidence rates , risk factors , prestroke therapy , and survival in CE/AF stroke from a prospect i ve population -based registry , from 1985 to 2006 . Results : A total of 3,064 ischemic  strokes , including 572 ( 18.7 % ) CE/AF strokes , were recorded . Over the 22 years , a decrease in the incidence of overall CE/AF stroke was noted ( incidence rate ratio 0.9858 , 95 % confidence interval [ CI ] 0.9731–0.9986 ; p = 0.03 ) . We observed a higher prevalence of previous AF , previous myocardial infa rct ion , and patients aged > 70 years in CE/AF stroke ( p < 0.0001 ) whereas hypercholesterolemia was more prevalent in other ischemic strokes ( p = 0.003 ) . A significant increase in the use of anticoagulants and antiplatelet agents  was noted , and was particularly pronounced for CE/AF stroke with previous AF . For CE/AF stroke , survival rates were 72 % at 1 month ( 95 % CI 0.68–0.76 ) , 52 % at 1 year ( 95 % CI 0.48–0.56 ) , and 43 % at 2 years ( 95 % CI 0.39–0.48 ) , and remained lower than those of other ischemic stroke . Conclusions : The decrease in the incidence of cardioembolic/atrial fibrillation stroke in our study was probably due to a slight increase in the utilization of antithrombotic therapy in patients with atrial fibrillation , but the use of such therapies will have to increase further because of the expected aging of the population in coming years . AF = atrial fibrillation ; CE = cardioembolic ; CI = confidence interval ; IRR = incidence rate ratios Background Only a few population -based cohort studies have investigated the impact of  atrial fibrillation ( AF ) on stroke in Japan . Methods A total of 10 929 participants ( 4147 men and 6782 women ) were included in this population -based prospect i ve cohort study . Baseline data , including  electrocardiograms ( ECGs )  to ascertain AF status , were obtained from April 1992 through July 1995 in 12 areas in Japan . Cox proportional hazards models were used to analyze the association of AF with stroke . Results A total of 54 participants had AF ( 0.49 % ) . The mean follow-up period was 10.7 years , during which 405 strokes were identified ; 12 of these occurred in participants with AF . The crude incidence of stroke in participants with and without AF was 14.9 and 4.5 per 1000 person-years in men , respectively , and 39.3 and 2.7 per 1000 person-years in women . After adjusting for geographical area , sex , age , smoking status , drinking status , obesity , hypertension , dyslipidemia , and diabetes mellitus , the hazard ratios ( 95 % confidence interval ) of AF in all participants and in male and female participants were 4.11 ( 2.28–7.41 ) , 2.12 ( 0.77–5.84 ) , and 10.6 ( 5.01–22.4 ) , respectively . The population attributable fraction ( PAF ) of stroke caused by AF was 2.2 % ; the PAFs were 1.0 % and 3.6 % in men and women , respectively . Conclusions The present Japanese population -based prospect i ve cohort study showed that AF is a major risk factor for stroke , especially in women OBJECTIVE This study was performed to characterize the risk of stroke in elderly patients with recurrent intermittent atrial fibrillation ( AF ) . BACKGROUND Although intermittent AF is common , relatively little is known about the attendant risk of stroke . METHODS A longitudinal cohort study was performed comparing 460 participants with intermittent AF with 1,552 with sustained AF treated with aspirin in the Stroke Prevention in Atrial Fibrillation studies and followed for a mean of two years . Independent risk factors for ischemic stroke were identified by multivariate analysis . RESULTS Patients with intermittent AF were , on average , younger ( 66 vs. 70 years , p < 0.001 ) , were more often women ( 37 % vs. 26 % p < 0.001 ) and less often had heart failure ( 11 % vs. 21 % , p < 0.001 ) than those with sustained AF . The annualized rate of ischemic stroke was similar for those with intermittent ( 3.2 % ) and sustained AF ( 3.3 % ) . In patients with intermittent AF , independent predictors of ischemic stroke were advancing age ( relative risk [ RR ] = 2.1 per decade , p < 0.001 ) , hypertension ( RR = 3.4 , p = 0.003 ) and prior stroke ( RR = 4.1 , p = 0.01 ) . Of those with intermittent AF predicted to be high risk ( 24 % ) , the observed stroke rate was 7.8 % per year ( 95 % confidence interval 4.5 to 14 ) . CONCLUSIONS In this large cohort of AF patients given aspirin , those with intermittent AF had stroke rates similar to patients with sustained AF and similar stroke risk factors . Many elderly patients with recurrent intermittent AF have substantial rates of stroke and likely benefit from anticoagulation . High-risk patients with intermittent AF can be identified using the same clinical criteria that apply to patients with sustained AF OBJECTIVES The purpose of this study was to investigate predictors of bleeding in a cohort of anticoagulated patients and to evaluate the predictive value of several bleeding risk stratification schemas . BACKGROUND The risk of bleeding during antithrombotic therapy in patients with atrial fibrillation ( AF ) is not homogeneous , and several clinical risk factors have been incorporated into clinical bleeding risk stratification schemas . Current risk stratification schemas for bleeding during anticoagulation therapy have been based on complex scoring systems that are difficult to apply in clinical practice , and few have been derived and vali date d in AF cohorts . METHODS We investigated predictors of bleeding in a cohort of 7,329 patients with AF participating in the SPORTIF ( Stroke Prevention Using an ORal Thrombin Inhibitor in Atrial Fibrillation ) III and V clinical trials and evaluated the predictive value of several risk stratification schemas by multivariate analysis . Patients were anticoagulated orally with either adjusted-dose warfarin ( target international normalized ratio 2 to 3 ) or fixed-dose ximelagatran 36 mg twice daily . Major bleeding was central ly adjudicated , and concurrent aspirin therapy was allowed in patients with clinical atherosclerosis . RESULTS By multivariate analyses , significant predictors of bleeding were concurrent aspirin use ( hazard ratio [ HR ] : 2.10 ; 95 % confidence interval [ CI ] : 1.59 to 2.77 ; p < 0.001 ) ; renal impairment ( HR : 1.98 ; 95 % CI : 1.42 to 2.76 ; p < 0.001 ) ; age 75 years or older ( HR : 1.63 ; 95 % CI : 1.23 to 2.17 ; p = 0.0008 ) ; diabetes ( HR : 1.47 ; 95 % CI : 1.10 to 1.97 ; p = 0.009 ) , and heart failure or left ventricular dysfunction ( HR : 1.32 ; 95 % CI : 1.01 to 1.73 ; p = 0.041 ) . Of the tested schemas , the new HAS-BLED ( Hypertension , Abnormal Renal/Liver Function , Stroke , Bleeding History or Predisposition , Labile INR , Elderly , Drugs/Alcohol Concomitantly ) score performed best , with a stepwise increase in rates of major bleeding with increasing HAS-BLED score ( p(trend ) < 0.0001 ) . The c statistic for bleeding varied between 0.50 and 0.67 in the overall entire cohort and 0.68 among patients naive to warfarin at baseline ( n = 769 ) . CONCLUSIONS This analysis identifies diabetes and heart failure or left ventricular dysfunction as potential risk factors for bleeding in AF beyond those previously recognized . Of the contemporary bleeding risk stratification schemas , the new HAS-BLED scheme offers useful predictive capacity for bleeding over previously published schemas and may be simpler to apply Background —Previous studies provide conflicting results about whether women are at higher risk than men for thromboembolism in the setting of atrial fibrillation ( AF ) . We examined data from a large contemporary cohort of AF patients to address this question . Methods and Results —We prospect ively studied 13 559 adults with AF and recorded data on patients ’ clinical characteristics and the occurrence of incident hospitalizations for ischemic stroke , peripheral embolism , and major hemorrhagic events through search ing vali date d computerized data bases and medical record review . We compared event rates by patient sex using multivariable log-linear regression , adjusting for clinical risk factors for stroke , and stratifying by warfarin use . We identified 394  ischemic stroke and peripheral embolic events during 15 494 person-years of follow-up off warfarin . After multivariable analysis , women had higher annual rates of thromboembolism off warfarin than did men ( 3.5 % versus 1.8 % ; adjusted rate ratio [ RR ] , 1.6 ; 95 % CI , 1.3 to 1.9 ) . There was no significant difference by sex in 30-day mortality after thromboembolism ( 23 % for both ) . Warfarin use was associated with significantly lower adjusted thromboembolism rates for both women and men ( RR , 0.4 ; 95 % CI , 0.3 to 0.5 ; and RR , 0.6 ; 95 % CI , 0.5 to 0.8 , respectively ) , with similar annual rates of major hemorrhage ( 1.0 % and 1.1 % , respectively ) . Conclusions —Women are at higher risk than men for AF-related thromboembolism off warfarin . Warfarin therapy appears be as effective in women , if not more so , than in men , with similar rates of major hemorrhage . Female sex is an independent risk factor for thromboembolism and should influence the decision to use anticoagulant therapy in persons with AF BACKGROUND Atrial fibrillation ( AF ) is an important public health problem . This arrhythmia is common and associated with a high risk of stroke . Further , appropriate interventions in AF can reduce the risk of stroke by approximately 68 % . Population studies show that a large group of patients have intermittent or chronic AF that remains unrecognized . If a simple screening test for this arrhythmia could be developed and vali date d , application of the technique across population s might identify AF patients for early treatment , potentially reducing the incidence of stroke . In this study , we sought to determine whether individuals taken from the general community could be taught to find and classify the pulse of another as very irregular , implying AF , or regular , implying normal sinus rhythm ( NSR ) . The aim was to establish that pulse examination for potential AF could be performed by individuals with sufficient sensitivity and specificity to be effectively used as a screening procedure for this medically important arrhythmia . METHODS We enrolled 178 subjects selected from the general community from four centers . Subjects received st and ardized education on the medical importance of AF and its signature , a very irregular pulse . A technique for palpating and characterizing the rhythm of the radial pulse was also taught . Without further coaching , subjects were then asked to find their pulse and then to find and classify the pulse of two models r and omly presented who may or may not have had AF . RESULTS Of the 178 subjects tested , 92 % were able to find their own pulse ; 17 ( 9.6 % ) were unable to find the pulse of one or both patient models and were , therefore , excluded from the study . Of the remaining 161 subjects , 76 % ( 122 of 161 ) correctly identified the pulse in an AF model , and 86 % ( 139 of 161 ) correctly identified the pulse in an NSR model . Results did not statistically differ as a function of age , educational status , or location . DISCUSSION This multicenter trial established that given minimal st and ardized instructions , subjects from the general community can reliably and consistently find both their pulse as well as the pulse of another and to differentiate a regular pulse from a very irregular pulse . If similar educational programs were widely applied across large population s , periodic screening for AF might lead to earlier diagnosis and appropriate treatment for patients who have this major risk factor for stroke . These screening programs should be focused on the population over the age of 55 where the risk of stroke in AF increases with each decade Background —It is unknown if brief episodes of device-detected atrial fibrillation ( AF ) increase thromboembolic event ( TE ) risk . Methods and Results —TRENDS was a prospect i ve , observational study enrolling patients with ≥1 stroke risk factor ( heart failure , hypertension , age ≥65 years , diabetes , or prior TE ) receiving pacemakers or defibrillators that monitor atrial tachycardia (AT)/AF burden ( defined as the longest total AT/AF duration on any given day during the prior 30-day period ) . This time-varying exposure was up date d daily during follow-up and related to TE risk . Annualized TE rates were determined according to AT/AF burden subsets : zero , low ( < 5.5 hours [ median duration of subsets with nonzero burden ] ) , and high ( ≥5.5 hours ) . A multivariate Cox model provided hazard ratios including terms for stroke risk factors and time-varying AT/AF burden and antithrombotic therapy . Patients ( n=2486 ) had at least 30 days of device data for analysis . During a mean follow-up of 1.4 years , annualized TE risk ( including transient ischemic attacks ) was 1.1 % for zero , 1.1 % for low , and 2.4 % for high burden subsets of 30-day windows . Compared with zero burden , adjusted hazard ratios ( 95 % CIs ) in the low and high burden subsets were 0.98 ( 0.34 to 2.82 , P=0.97 ) and 2.20 ( 0.96 to 5.05 , P=0.06 ) , respectively . Conclusions —The TE rate was low compared with patients with traditional AF with similar risk profiles . The data suggest that TE risk is a quantitative function of AT/AF burden . AT/AF burden ≥5.5 hours on any of 30 prior days appeared to double TE risk . Additional studies are needed to more precisely investigate the relationship between stroke risk and AT/AF burden Background : While atrial fibrillation ( AF ) increases the risk of cardioembolic stroke , some ischemic strokes in AF patients are noncardioembolic . Objectives : To assess ischemic stroke mechanisms in AF and to compare their responses to antithrombotic therapies . Methods : On-therapy analyses of ischemic strokes occurring in 3,950 participants in the Stroke Prevention in Atrial Fibrillation I – III clinical trials . Strokes were classified by presumed mechanism according to specified neurologic features by neurologists unaware of antithrombotic therapy . Results : Of 217 ischemic strokes , 52 % were classified as probably cardioembolic , 24 % as noncardioembolic , and 24 % as of uncertain cause ( i.e. , 68 % of classifiable infa rcts were deemed cardioembolic ) . Compared to those receiving placebo or no antithrombotic therapy , the proportion of cardioembolic stroke was lower in patients taking adjusted-dose warfarin ( p = 0.02 ) , while the proportion of noncardioembolic stroke was lower in those taking aspirin ( p = 0.06 ) . Most ( 56 % ) ischemic strokes occurring in AF patients taking adjusted-dose warfarin were noncardioembolic vs. 16 % of strokes in those taking aspirin . Adjusted-dose warfarin  reduced cardioembolic strokes by 83 % ( p < 0.001 ) relative to aspirin . Cardioembolic strokes were particularly disabling ( p = 0.05 ) . Conclusions : Most ischemic strokes in AF patients are probably cardioembolic , and these are sharply reduced by adjusted-dose warfarin . Aspirin in AF patients appears to primarily reduce noncardioembolic strokes .  AF patients at highest risk for stroke have the highest rates of cardioembolic stroke and have the greatest reduction in stroke by warfarin CONTEXT Prior risk stratification schemes for atrial fibrillation ( AF ) have been based on r and omized trial cohorts or Medicare administrative data bases , have included patients with established AF , and have focused on stroke as the principal outcome . OBJECTIVE To derive risk scores for stroke alone and stroke or death in community-based individuals with new-onset AF . DESIGN , SETTING , AND PARTICIPANTS Prospect i ve , community-based , observational cohort in Framingham , Mass. We identified 868 participants with new-onset AF , 705 of whom were not treated with warfarin at baseline . Risk scores for stroke ( ischemic or hemorrhagic ) and stroke or death were developed with censoring when warfarin initiation occurred during follow-up . Event rates were examined in low-risk individuals , as defined by the risk score and 4 previously published risk schemes . MAIN OUTCOME MEASURES Stroke and the combination of stroke or death . RESULTS During a mean follow-up of 4.0 years free of warfarin use , stroke alone occurred in 83 participants and stroke or death occurred in 382 participants . A risk score for stroke was derived that included the following risk predictors : advancing age , female sex , increasing systolic blood pressure , prior stroke or transient ischemic attack , and diabetes . With the risk score , 14.3 % of the cohort had a predicted 5-year stroke rate < or = 7.5 % ( average annual rate < or = 1.5 % ) , and 30.6 % of the cohort had a predicted 5-year stroke rate < or = 10 % ( average annual rate < or = 2 % ) . Actual stroke rates in these low-risk groups were 1.1 and 1.5 per 100 person-years , respectively . Previous risk schemes classified 6.4 % to 17.3 % of subjects as low risk , with actual stroke rates of 0.9 to 2.3 per 100 person-years . A risk score for stroke or death is also presented . CONCLUSION These risk scores can be used to estimate the absolute risk of an adverse event in individuals with AF , which may be helpful in counseling patients and making treatment decisions BACKGROUND The presence of vascular disease ( peripheral artery disease [ PAD ] and /or myocardial infa rct ion [ MI ] ) may impact on the risk of stroke and death among patients with incident atrial fibrillation ( AF ) . To test this hypothesis , we analyzed data from a large Danish prospect i ve cohort , the Danish Diet , Cancer and Health ( DCH ) study , to assess the risk of stroke or death among those who developed AF according to concomitant presence of vascular disease . METHODS A prospect i ve cohort study of 57 , 053 persons ( 27 , 178 men and 29 , 876 women , respectively ) , aged between 50 and 64 years . The risk of stroke or death for patients with vascular disease was assessed amongst 3315 patients with incident AF ( mean age , 67.1years ; 2130 men , 1185 women ) using Cox proportional hazard models , after a median follow-up of 4.8 years . RESULTS Of the subjects with AF , 417 ( 12.6 % ) had ' vascular disease ' ( PAD and /or prior MI ) . The risk of the primary endpoint ( stroke or death ) was significantly higher in patients with vascular disease at 1-year follow-up ( crude hazard ratio [ HR ] 2.51 [ 1.91 - 3.29 ] ) , with corresponding crude HRs for PAD and MI being 3.51 ( 2.40 - 5.13 ) , and 1.99 ( 1.46 - 2.72 ) , respectively . For the secondary endpoints of death or stroke individually , these risk estimates were similar ( crude HR 2.48 [ 1.89 - 3.26 ] and 1.77 [ 1.18 - 2.66 ] , respectively ) . After adjustment for risk factors within the CHADS(2 ) score , the adjusted HR for the primary endpoint ( stroke or death ) in patients with vascular disease was 1.91 ( 1.44 - 2.54 ) , which was also significant for death ( 1.97 [ 1.48 - 2.62 ] ) . CONCLUSION Vascular disease ( prior MI and PAD ) is an independent risk factor for the primary endpoint of ' stroke or death ' in patients with AF , even after adjustment for the CHADS(2 ) risk score , although this is driven by the impact on mortality . This reaffirms that patients with vascular disease represent a ' high-risk ' population , which necessitates proactive management of all cardiovascular risk factors and effective thromboprophylaxis ( i.e. oral anticoagulation ) , which has been shown to significantly reduce the risk of stroke and death in AF
Few models had addressed the cumulative nature of risk factors where a combination of risk factors would confer a greater risk than either factor alone .
In patients at high risk of stroke , anticoagulation is cost effective , but not for those with a low risk of stroke .
The risk of stroke in atrial fibrillation ( AF ) needs to be assessed in each patient to determine the clinical and cost-effectiveness of thromboprophylaxis , with the aim of appropriate use of antithrombotic therapy .
To achieve this , stroke risk factors in AF population s need to be identified and stroke risk stratification models have been devised on the basis of these risk factors .
In this article , we firstly provide a systematic review of studies examining the attributable stroke risk of various clinical , demographic and echocardiographic patient characteristics in AF population s. Secondly , we performed a systematic review of published stroke risk stratification models , in terms of the results of the review of stroke risk factors and their ability to accurately discriminate between different levels of stroke risk .