Risk factors for stroke in patients with nonrheumatic atrial fibrillation: a case-control study. Assessment of three schemes for stratifying stroke risk in patients with nonvalvular atrial fibrillation. An analysis of the lowest effective intensity of prophylactic anticoagulation for patients with nonrheumatic atrial fibrillation. Acute stroke with atrial fibrillation. The Copenhagen Stroke Study. RISK OF STROKE IN NON-RHEUMATIC ATRIAL FIBRILLATION 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. Prognostic implications of left atrial spontaneous echo contrast in nonvalvular atrial fibrillation. Antithrombotic Treatment Patterns in Patients with Newly Diagnosed Nonvalvular Atrial Fibrillation: The GLORIA-AF Registry, Phase II. Epidemiology of ischemic stroke from atrial fibrillation in Dijon, France, from 1985 to 2006 Transesophageal echocardiographic correlates of thromboembolism in high-risk patients with nonvalvular atrial fibrillation. The Stroke Prevention in Atrial Fibrillation Investigators Committee on Echocardiography. Patients with nonvalvular atrial fibrillation at low risk of stroke during treatment with aspirin: Stroke Prevention in Atrial Fibrillation III Study. The SPAF III Writing Committee for the Stroke Prevention in Atrial Fibrillation Investigators. Prevalence, clinical profile, and cardiovascular outcomes of atrial fibrillation patients with atherothrombosis. Effect of Age on Stroke Prevention Therapy in Patients With Atrial Fibrillation: The Atrial Fibrillation Investigators Impact of a patient decision aid on care among patients with nonvalvular atrial fibrillation: a cluster randomized trial Focused 2012 update of the Canadian Cardiovascular Society atrial fibrillation guidelines: recommendations for stroke prevention and rate/rhythm control. Stroke event rates in anticoagulated patients with paroxysmal atrial fibrillation. Factors relevant to preventing embolic stroke in patients with non-rheumatic atrial fibrillation.
PURPOSE R and omized controlled trials have demonstrated that anticoagulant therapy is very effective at preventing stroke among patients with nonrheumatic atrial fibrillation . However , these trials have reported too few strokes for powerful risk factor analysis . Observational studies may provide additional information . The purpose of this study was to identify risk factors in a larger number of patients with stroke and nonrheumatic atrial fibrillation , using case-control methodology . PATIENTS AND METHODS We identified all patients discharged from one hospital over an 8-year period who met our case definition of nonrheumatic atrial fibrillation and ischemic stroke ( n = 134 ) , and compared them with contemporaneous control subjects who were discharged with nonrheumatic atrial fibrillation without stroke ( n = 131 ) . RESULTS Cases and controls were similar in terms of duration of atrial fibrillation ; proportion with paroxysmal atrial fibrillation ; percentage with a past medical history of angina , myocardial infa rct ion , congestive heart failure , diabetes , or smoking ; and mean left atrial size . In contrast , cases were significantly older than controls ( 78.5 versus 74.8 years , p = 0.002 ) and more likely to have a history of hypertension ( 55 % versus 38 % , p = 0.0093 ) . The relative odds for stroke was 1.91 for patients with hypertension , 1.73 for patients older than 75 years , and 3.26 for patients with both factors . CONCLUSIONS Our analysis suggests that age and hypertension should be considered when deciding upon long-term anticoagulant therapy to prevent stroke in patients with nonrheumatic atrial fibrillation PURPOSE The risk of ischemic stroke varies widely among patients with nonvalvular atrial fibrillation , influencing the choice of prophylactic antithrombotic therapy . We assessed three schemes for stroke risk stratification in these patients who were treated with aspirin and who did not have prior cerebral ischemia . SUBJECTS AND METHODS Criteria from three schemes of risk stratification were applied to a longitudinally observed cohort of patients with atrial fibrillation who did not have prior cerebral ischemia and who were treated with aspirin alone or aspirin combined with low , ineffective doses of warfarin in a multicenter clinical trial . The ability of the schemes to identify patients at high ( > /=6 % ) , low ( < /=2 % ) , and intermediate annual risks of ischemic stroke was assessed . RESULTS During a mean follow-up of 1.8 years , 48 ischemic strokes occurred among 1,073 patients with atrial fibrillation who were taking aspirin ( rate = 2.5 per 100 person-years ) . Each of the three schemes predicted stroke and disabling stroke , and successfully identified patients at low risk ( observed stroke rates of 0.3 to 1.1 per 100 person-years ) , although the fractions of the cohort that were categorized as low risk varied from 14 % to 45 % . The observed rates of ischemic stroke among patients categorized as high risk ranged from 3.5 to 7.2 per 100 person-years among the stratification schemes . Two schemes considered all patients > 75 years old as high risk ( observed stroke rate 4.2 per 100 person-years ) , while the remaining scheme classified one third of patients in this age group as low risk ( observed stroke rate 0.6 per 100 person-years ) . CONCLUSIONS When tested in a large cohort of patients with atrial fibrillation who were treated with aspirin  , available risk-stratification schemes successfully identified patients with low rates of ischemic stroke , but less consistently identified high-risk patients BACKGROUND To avert major hemorrhage , physicians need to know the lowest intensity of anticoagulation that is effective in preventing stroke in patients with atrial fibrillation . Since the low rate of stroke has made it difficult to perform prospect i ve studies to resolve this issue , we conducted a case-control study . METHODS We studied 74 consecutive patients with atrial fibrillation who were admitted to our hospital from 1989 through 1994 after having an ischemic stroke while taking warfarin .  For each patient with stroke , three controls with nonrheumatic atrial fibrillation who were treated as out patients were r and omly selected from the 1994 registry of the anticoagulant-therapy unit ( 222 controls ) . We used the  international normalized ratio ( INR )  to measure the intensity of anticoagulation .  For the patients with stroke , we used INR at admission ; for the controls , we selected the INR that was measured closest to the month and day of the matched case patient 's hospital admission . RESULTS The risk of stroke rose steeply at INRs below 2.0 . At an INR of 1.7 , the adjusted odds ratio for stroke , as compared with the risk at an INR of 2.0 , was 2.0 ( 95 percent confidence interval , 1.6 to 2.4 ) ; at an INR of 1.5 , it was 3.3 ( 95 percent confidence interval , 2.4 to 4.6 ) ; and at an INR of 1.3 , it was 6.0 ( 95 percent confidence interval , 3.6 to 9.8 ) . Other independent risk factors were previous stroke ( odds ratio , 10.4 ; 95 percent confidence interval , 4.4 to 24.5 ) , diabetes mellitus ( odds ratio , 2.95 ; 95 percent confidence interval , 1.3 to 6.5 ) , hypertension ( odds ratio , 2.5 ; 95 percent confidence interval , 1.1 to 5.7 ) , and current smoking ( odds ratio , 5.7 ; 95 percent confidence interval , 1.4 to 24.0 ) . CONCLUSIONS Among patients with atrial fibrillation , anticoagulant prophylaxis is effective at INRs of 2.0 or greater . Since previous studies have indicated that the risk of hemorrhage rises rapidly at INRs greater than 4.0 to 5.0 , tight control of anticoagulant therapy to maintain the INR between 2.0 and 3.0 is a better strategy than targeting lower , less effective levels of anticoagulation 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 Estimates of the risk of stroke for men with non-rheumatic atrial fibrillation were obtained from two large cohort studies --the Whitehall Study of London Civil Servants and the British  Regional Heart Study . The first cohort provided an estimated relative risk of stroke of 6.9 compared with controls . This increased risk confirms that of the other prospect i ve estimate , 5.6 , found in the Framingham study . In the second cohort only one of the men at risk had a stroke , and the risk estimate did not differ significantly from unity . The absolute rates of stroke in both cohorts were lower than those reported in the Framingham study , implying a lesser potential benefit from preventive measures . These lower rates should be considered in the planning of trials . The risk of stroke was significantly associated with raised systolic or diastolic blood pressure but not with age or coronary heart disease 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 ) OBJECTIVES This study examined the influence of left atrial spontaneous echo contrast on the subsequent stroke or embolic event rate and on survival in patients with nonvalvular atrial fibrillation . BACKGROUND Left atrial spontaneous echo contrast is associated with atrial fibrillation and a history of previous stroke or other embolic events . However , the prognostic implication s of spontaneous contrast in patients with nonvalvular atrial fibrillation are unknown . METHOD The study group comprised 272 consecutive patients with nonvalvular atrial fibrillation undergoing transesophageal echocardiography .  Clinical and echocardiographic data were collected at baseline , and patients were prospect ively followed up , and all strokes , other embolic events and deaths were documented . The relation between spontaneous contrast at baseline and subsequent stroke , other embolic events and survival was analyzed . RESULTS Left atrial spontaneous echo contrast was detected at baseline in 161 patients ( 59 % ) . The mean follow-up was 17.5 months . The stroke or other embolic event rate was 12%/year ( 15 strokes , 3 transient ischemic attacks , 2 peripheral embolisms ) in patients with , compared with 3%/year ( 5 strokes ) in patients without , baseline spontaneous contrast ( p = 0.002 ) . In 149 patients without previous thromboembolism , the event rate was 9.5%/year in patients with and 2.2%/year in patients without spontaneous contrast ( p = 0.003 ) . There were 25 deaths in patients with and 11 deaths in patients without spontaneous contrast . Patients with spontaneous contrast had significantly reduced survival ( p = 0.025 ) . On multivariate analysis , spontaneous contrast was the only positive predictor ( odds ratio 3.5 , p = 0.03 ) and warfarin therapy on follow-up the only negative predictor ( odds ratio 0.23 , p = 0.02 ) of subsequent stroke or other embolic events . CONCLUSIONS Transesophageal echocardiography can risk stratify patients with nonvalvular atrial fibrillation by identifying left atrial spontaneous echo contrast . These patients have both a significantly higher risk of developing stroke or other embolic events and a reduced survival , and they may represent a subgroup in whom the risk/benefit ratio of anticoagulation may be most favorable BACKGROUND The Global Registry on Long-Term Oral Antithrombotic Treatment in Patients with Atrial Fibrillation ( GLORIA-AF ) was design ed to provide prospect ively collected information on patients with newly diagnosed nonvalvular atrial fibrillation at risk of stroke , with the aim of addressing treatment patterns and questions of effectiveness and safety . METHODS AND RESULTS In this predefined analysis from GLORIA-AF , the baseline characteristics and initial antithrombotic management of the first 10,000 patients in Phase II of this large Registry Program are presented . Overall , 32.3 % of patients received vitamin K antagonists ( VKAs ) and 47.7 % received non-VKA oral anticoagulants ( NOACs ) , while 12.3 % received antiplatelet treatment and 7.6 % did not receive any antithrombotic treatment . Among patients with CHA2DS2-VASc score ≥2 , 6.7 % received no antithrombotic treatment and 10.0 % received aspirin . In Europe , treatment with dabigatran was as common as treatment with VKAs ( 38.8 % and 37.8 % , respectively ) . More than half of the patients were treated with NOACs ( 52.4 % ) , while antiplatelet treatment was given to 5.7 % , and 4.1 % did not receive any antithrombotic treatment . In North America , treatment with dabigatran  ( 25.0 % ) was as common as with VKAs ( 26.1 % ) , but overall NOAC use was more common ( 52.1 % ) than with VKAs ( 26.1 % ) ; however , 14.1 % received antiplatelet treatment , while 7.6 % received no antithrombotic treatment . In Asia , treatment with VKAs ( 31.9 % ) was more prevalent than NOACs ( 25.5 % ) , but antiplatelet treatment was given to 25.8 % , and 16.9 % did not receive any antithrombotic treatment . In Asia , only 60.7 % of patients with high stroke risk received oral anticoagulants ( OACs ) . Paroxysmal atrial fibrillation and minimally symptomatic ( or asymptomatic ) patients were often undertreated with OACs . CONCLUSION In this analysis , OAC use was high in Europe and North America , with overall NOAC use higher than VKA use . A considerable percentage of high-risk patients in North America still received antiplatelet treatment or were untreated , while Asian patients had a high proportion of aspirin use and nontreatment 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 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 ) . CONTEXT Nonvalvular atrial fibrillation ( AF ) carries an increased risk for stroke , but absolute rates of stroke vary widely within the broad spectrum of AF patients . OBJECTIVE To prospect ively vali date a risk stratification scheme identifying patients with AF with low rates of stroke when given aspirin .  DESIGN Prospect i ve cohort study with mean duration of follow-up of 2.0 years , conducted between 1993 and 1997 . SETTING Outpatient clinics affiliated with academic medical centers . PATIENTS Patients with AF categorized as " low risk " based on the absence of 4 prespecified thromboembolic risk factors : recent congestive heart failure or left ventricular fractional shortening of 25 % or less , previous thromboembolism , systolic blood pressure greater than 160 mm Hg , or female sex at age older than 75 years . INTERVENTION All participants given aspirin , 325 mg/d . MAIN OUTCOME MEASURES Ischemic stroke ( considered disabling when Rankin score was II or worse 1 - 3 months later ) and systemic embolism ( primary events ) . RESULTS Among 892 participants , the mean ( SD ) age was 67 ( 10 ) years , 78 % were men , and histories of hypertension , diabetes , and ischemic heart disease were present in 46 % , 13 % , and 16 % , respectively . The rate of primary events was 2.2 % per year ( 95 % confidence interval [ CI ] , 1.6%-3.0 % ) , of ischemic stroke was 2.0 % per year ( 95 % CI , 1.5%-2.8 % ) , and of disabling ischemic strokes was 0.8 % per year ( 95 % CI , 0.5%-1.3 % ) . Those with a history of hypertension had a higher rate of primary events ( 3.6 % per year ) than those with no history of hypertension ( 1.1 % per year ) ( P<.001 ) . The rate of disabling ischemic stroke was low in those with and without a history of hypertension ( 1.4 % per year and 0.5 % per year , respectively ) . The rate of major bleeding during aspirin therapy was 0.5 % per year . CONCLUSION Patients with AF who have relatively low rates of ischemic stroke , particularly disabling stroke , during treatment with aspirin can be reliably identified 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 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 Background : Too few patients with nonvalvular atrial fibrillation ( NVAF ) receive appropriate antithrombotic therapy . We tested the short-term ( primary outcome ) and long-term ( secondary outcome ) effect of a patient decision aid on the appropriateness of antithrombotic therapy among patients with NVAF . Methods : We conducted a cluster r and omized trial with blinded outcome assessment involving 434 NVAF patients from 102 community-based primary care practice s. Patients in the intervention group received a self-administered booklet and audiotape decision aid tailored to their personal stroke risk profile . Patients in the control group received usual care . The primary outcome measure was change in antithrombotic therapy at 3 months . Appropriateness of therapy was defined using the American College of Chest Physicians ( ACCP ) recommendations . Results : The mean patient age was 72 years , and the median duration of NVAF was 5 years . In the control group , there was a 3 % decrease over 3 months in the number of patients receiving therapy appropriate to their risk of stroke ( 40 % [ 85/215 ] at baseline v. 37 % [ 79/215 ] at 3 months ) . In the intervention group , the number of patients receiving therapy appropriate to their stroke risk increased by 9 % ( 32 % [ 69/219 ] at baseline v. 41 % [ 89/219 ] at 3 months ) . Although the proportion of patients whose therapy met the ACCP treatment recommendations did not differ between study arms at baseline ( p = 0.11 ) or 3 months ( p = 0.44 ) , there was a 12 % absolute improvement in the number of patients receiving appropriate care in the intervention group compared with the control group at 3 months ( p = 0.03 ) . The beneficial effect of the decision aid did not persist ( p = 0.44 for differences between study arms after 12 months ) . Interpretation : There was short-term improvement in the appropriateness of antithrombotic care among patients with NVAF who were exposed to a decision aid , but the improvement did not persist 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 AIMS To test the hypothesis that stroke and systemic embolic events ( SEE ) in the stroke prevention using an oral thrombin inhibitor in atrial fibrillation ( SPORTIF ) III and V trials are different between paroxysmal and persistent atrial fibrillation ( AF ) . METHODS Data analysis from two cohorts of patients enrolled in the prospect i ve SPORTIF III and V clinical trials ( n = 7329 ) ; 836 subjects ( 11.4 % ) with paroxysmal AF [ mean age 70.1 years ( SD = 9.5 ) ] were compared with 6493 subjects with persistent AF for this ancillary study . RESULTS The annual event rates for stroke/SEE are 1.73 % for persistent AF and 0.93 % for paroxysmal AF . In a multivariate analysis , after adjusting for stroke risk factors , gender and aspirin usage , the differences remained statistically significant with a higher hazard ratio ( HR ) for stroke/SEE in persistent AF [ vs. paroxysmal AF , HR 1.87 , 95 % confidence interval ( CI ) 1.04 - 3.36 ; P = 0.037 ] . In ' high risk ' patients ( with > or=2 stroke risk factors ) annual event rates for stroke/SEE were 2.08 % for persistent AF and 1.27 % for paroxysmal AF ( adjusted HR = 1.68 , 95 % CI 0.91 - 3.1 , P = 0.098 ) . Elderly patients had annual event rates for stroke/SEE of 2.38 % for persistent AF and 1.13 % for paroxysmal AF ( adjusted HR = 2.27 , 95 % CI 0.92 - 5.59 , P = 0.075 ) . Vitamin K antagonist (VKA)-naive paroxysmal AF patients had a 1.89%/year stroke/SEE rate , compared with 0.61 % for previous VKA takers ( HR = 0.33 , 95 % CI 0.11 - 1.01 , P = 0.052 ) . CONCLUSION In this large clinical trial cohort of anticoagulated AF patients , those with paroxysmal AF had stroke rates which were lower than for patients with persistent AF , although both groups had broadly similar stroke risk factors . Subjects with paroxysmal AF at ' high risk ' had stroke/SEE rates that were not significantly different to persistent AF subjects Whether or not to treat patients with non-rheumatic atrial fibrillation with anticoagulants to prevent embolic stroke is a dilemma for physicians . If r and omized trials , currently underway , demonstrate a beneficial effect , the dilemma will not be solved because not all of the relevant factors can be addressed by trials . We used current knowledge about non-rheumatic atrial fibrillation and a method of obtaining patient-derived weights for avoiding stroke from eight medically trained subjects , to determine the overall benefit of anticoagulants and to see what factors were relevant and what effect each might have in deciding whether to use anticoagulant therapy . Using st and ard assumptions , anticoagulants gave an expected benefit for all subjects . The expected benefit ( expressed in terms of lives per 1000 saved due to anticoagulants ) varied between 5.4 and 46.7 . This benefit remained for all subjects when we did a sensitivity analysis for different rates of stroke prevented by anticoagulants and different rates of intracranial hemorrhage caused by anticoagulants . When we used different baseline rates of stroke and different impacts of major hemorrhagic complications the benefit disappeared for 3 and 4 subjects respectively . We found the factors that were most crucial to the decision will not be included in r and omized trials ; the weight that an individual would place on avoiding embolic stroke vs the risk of intracranial bleeding from anticoagulant therapy ; and the rate of embolic stroke that could be expected for the subject at risk . Factors which will be measured in r and omized trials , will change results less substantially : the increased risk of major hemorrhages ; the proportion of strokes that could be prevented by treatment ; the increase in risk of intracranial hemorrhage . This method of analysis suggests that for most patients anticoagulants are beneficial and that the most important factor in determining this result is the value that subjects put on different outcomes
Female sex was inconsistently associated with stroke risk , whereas the evidence was inconclusive that either heart failure or coronary artery disease is independently predictive of stroke .
Conclusions : Four clinical features ( prior stroke/TIA , advancing age , hypertension , diabetes ) are consistent independent risk factors for stroke in atrial fibrillation patients .
Background : Absolute stroke rates vary widely among patients with nonvalvular atrial fibrillation .
To balance the benefits and risks of chronic antithrombotic prophylaxis , it is important to estimate the absolute risk of stroke for individual patients .