title: Bleeding during warfarin and aspirin therapy in patients with atrial fibrillation: the AFASAK 2 study. Atrial Fibrillation Aspirin and Anticoagulation. Stroke with intermittent atrial fibrillation: incidence and predictors during aspirin therapy. Stroke Prevention in Atrial Fibrillation Investigators. Stroke Incidence in Copenhagen, 1976–1988 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. Prospective cohort study to determine if trial efficacy of anticoagulation for stroke prevention in atrial fibrillation translates into clinical effectiveness Bleeding during antithrombotic therapy in patients with atrial fibrillation. The Stroke Prevention in Atrial Fibrillation Investigators. Age and the risk of warfarin-associated hemorrhage: the anticoagulation and risk factors in atrial fibrillation study. Predictors of major vascular events in patients with a transient ischemic attack or minor ischemic stroke and with nonrheumatic atrial fibrillation. European Atrial Fibrillation Trial (EAFT) Study Group. 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. Oral anticoagulant therapy in patients with nonrheumatic atrial fibrillation and risk of bleeding. A Multicenter Inception Cohort Study. Advanced Age, Anticoagulation Intensity, and Risk for Intracranial Hemorrhage among Patients Taking Warfarin for 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 people aged 65 and over. The SAFE study. Results of an open-label, prospective study of anticoagulant therapy for atrial fibrillation in an outpatient anticoagulation clinic.
abstract: BACKGROUND Treatment with warfarin sodium is effective for stroke prevention in atrial fibrillation but many physicians hesitate to prescribe it to elderly patients presumably because of the associated risk for bleeding and the inconvenience of frequent blood tests for the patients . METHODS In the Second Copenhagen Atrial Fibrillation , Aspirin , and Anticoagulation ( AFASAK 2 ) Study , we studied the rate of bleeding events associated with the incidence of thromboembolic events in patients receiving warfarin sodium , 1.25 mg/d ; warfarin sodium , 1.25 mg/d , plus aspirin , 300 mg/d ; aspirin , 300 mg/d ; or adjusted-dose warfarin therapy aim ing at an international normalized ratio of the prothrombin time ratio ( INR ) of 2.0 to 3.0 . The study was scheduled for 6 years from May 1 , 1993 , but owing to evidence of inefficiency of low-intensity therapy plus aspirin from another study it was prematurely terminated on October 2 , 1996 . Minor and major bleeding events were recorded prospect ively . The rate of bleeding was calculated using the Kaplan-Meier method and risk factors were identified by the Cox proportional hazards model . RESULTS Of 677 included patients , 130 ( median age , 77 years ; range , 67 - 89 years ) experienced bleeding . One woman and 12 men experienced major bleeding . Four had intracranial bleeding : 2 cases were fatal and 2 were nonfatal . During treatment with mini-dose warfarin , warfarin plus aspirin , aspirin , and adjusted-dose warfarin , the annual rate of major bleeding was 0.8 % , 0.3 % , 1.4 % , and 1.1 % , respectively ( P = .20 ) . After 3 years of treatment the cumulative rate of any bleeding was 24.7 % , 24.4 % , 30.0 % , and 41.1 % ( P = .003 ) , respectively . Increasing INRvalue ( P<.001 ) and prior myocardial infa rct ion ( P = .001 ) were independent risk factors for bleeding , whereas increasing age was not . CONCLUSIONS Fixed mini-dose warfarin and aspirin alone or in combination were associated with both minor and major bleeding . The small number of major bleeding events in patients receiving adjusted-dose warfarin therapy as compared with those receiving less intensive antithrombotic treatments and the finding of no significant influence of age on the risk for bleeding indicate that even elderly patients with atrial fibrillation tolerate adjusted-dose warfarin therapy ( INR , 2.0 - 3.0 ) 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 Background and Purpose Temporal trends in stroke incidence in Denmark have not been previously reported . The Copenhagen City Heart Study is a prospect i ve study based on a r and omly selected sample of an urban population of , initially , 19,698 participants followed since 1976 . Over a period of 12 years , we studied three important aspects of stroke incidence in 848 identified cases : temporal trends , dependence on age and sex , and comparison of responders and nonresponders . Methods The participants were invited to two health examinations at 5-year intervals . The participants who attended at least one of the two examinations are termed responders and those who attended none nonresponders . The cases of first-ever stroke were collected from responders , the National Patient Register , and the National Register of Deaths and were verified by study of hospital records and death certificates . Results For responders aged 35–64 years and ≥65 years , there were no significant changes in the weighted rates in four consecutive 3-year periods . There was a tendency toward decreasing rates among younger women , but not in older women or men . The age- and sex-adjusted rates per 1,000 ( based on the Danish population in 1982 ) in responders in the entire 12-year follow-up period were 1.61 in women , 2.67 in men , and 2.14 in both sexes combined . Stroke incidence rates increased exponentially with age in both sexes , with rates in men generally twice those in women , even in the ≥75 years of age group . Age-adjusted rates were higher in nonresponders than in responders . For women , this ratio was 1.7 ; for men , 1.1 . Conclusions The stroke incidence in Copenhagen is relatively high and has shown no decreasing tendency over the period 1976–1988 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 Abstract Objective : To determine whether trial efficacy of prophylaxis with warfarin for patients with atrial fibrillation at high risk of stroke translates into effectiveness in clinical practice . Design : Two year prospect i ve cohort study . Setting : District general hospital . Participants : 167 patients with atrial fibrillation and at high stroke risk who were eligible for anticoagulation Interventions : Long term anticoagulation with warfarin at adjusted doses to maintain an international normalised ratio of 2.0 - 3.0 Main outcome measures : Comparison of patient characteristics , comorbidity , anticoagulation control , stroke rate , and haemorrhagic complications with pooled data from five r and omised controlled trials . Results : Patients in the study group were seven years older ( 95 % confidence interval 4 to 10 ) and comprised 33 % more women than patients in the pooled trials . The international normalised ratio was in the target range for 61 % of the time ( range 37%-85 % ) , below for 26 % of the time ( range 8%-32 % ) , and above for 13 % of the time ( range 6%-26 % ) . The time that patients in the study group spent in the target range was significantly less than in the pooled analysis . The incidence of stroke in the study group ( 2.0 % per year , 0.7 % to 4.4 % ) was comparable to that of patients receiving warfarin in pooled studies ( 1.4 % , 0.8 % to 2.3 % ) . Per year the incidence of major ( 1.7 % v 1.6 % ) and minor ( 5.4 % v 9.2 % ) bleeding complications was also similar . Conclusion : Rates of stroke and major haemorrhage after anticoagulation in clinical practice were comparable to those obtained from pooled data from r and omised controlled studies for patients with atrial fibrillation at high risk of BACKGROUND The Stroke Prevention in Atrial Fibrillation II study compared warfarin vs aspirin for stroke prevention in atrial fibrillation . Bleeding complications importantly detracted from warfarin 's net effectiveness , particularly among older patients . OBJECTIVES To analyze bleeding complications according to assigned therapy . To identify risk factors for bleeding during anticoagulation . METHODS Eleven hundred patients ( mean age , 70 years ) were r and omized to 325 mg of aspirin daily ( enteric coated ) vs warfarin ( target prothrombin time ratio , 1.3 to 1.8 ; approximate international normalized ratio , 2.0 to 4.5 ) . Major hemorrhages were defined prospect ively . RESULTS The rate of major bleeding while receiving warfarin was 2.3 % per year ( 95 % confidence interval [ CI ] , 1.7 to 3.2 ) vs 1.1 % per year ( 95 % CI , 0.7 to 1.8 ) while receiving aspirin ( relative risk , 2.1 ; 95 % CI , 1.1 to 3.1 ; P = .02 ) . Intracranial hemorrhage occurred at 0.9 % per year ( 95 % CI , 0.5 to 1.5 ) with warfarin and 0.3 % per year ( 95 % CI , 0.1 to 0.8 ) with aspirin ( relative risk , 2.4 ; P = .08 ) . Age ( P = .006 ) , increasing number of prescribed medications ( P = .007 ) , and intensity of anticoagulation ( P = .02 ) were independent risks for bleeding at any site during anticoagulation . The rate of major hemorrhage was 1.7 % per year in patients aged 75 years or younger who received anticoagulation vs 4.2 % per year in older patients ( relative risk , 2.6 , P = .009 ) ; rates by age for intracranial bleeding were 0.6 % per year and 1.8 % per year , respectively ( P = .05 ) . CONCLUSION Advancing age and more intense anticoagulation increase the risk of major hemorrhage in patients given warfarin for stroke prevention OBJECTIVES To assess whether older age is independently associated with hemorrhage risk in patients with atrial fibrillation , whether or not they are taking warfarin therapy . DESIGN Cohort study . SETTING Integrated healthcare delivery system . Thirteen thous and five hundred fifty-nine adults with nonvalvular atrial fibrillation . MEASUREMENTS Patient data were collected from automated clinical and administrative data bases using previously vali date d search algorithms . Medical charts were review ed from patients hospitalized were for major hemorrhage ( intracranial , fatal , requiring > or=2 units of transfused blood , or involving a critical anatomic site ) . Age was categorized into four categories ( < 60 , 60 - 69 , 70 - 79 , and > or=80 ) , and multivariable Poisson regression was used to assess whether major hemorrhage rates increased with age , stratified by warfarin use and adjusted for other clinical risk factors for hemorrhage . RESULTS A total of 170 major hemorrhages were identified during 15,300 person-years of warfarin therapy and 162 major hemorrhages during 15,530 person-years off warfarin therapy . Hemorrhage rates rose with older age , with an average increase in hemorrhage rate of 1.2 ( 95 % confidence interval ( CI ) 1.0 - 1.4 ) per older age category in patients taking warfarin and 1.5 ( 95 % CI=1.3 - 1.8 ) in those not taking warfarin .  Intracranial hemorrhage rates were significantly higher in those aged 80 and older ( adjusted rate ratio=1.8 , 95 % CI=1.1 - 3.1 for those taking warfarin , adjusted rate ratio=4.7 , 95 % CI=2.4 - 9.2 for those not taking warfarin ) than in those younger than 80 . CONCLUSION Older age increases the risk of major hemorrhage , particularly intracranial hemorrhage , in patients with atrial fibrillation , whether or not they are taking warfarin .  Hemorrhage rates were generally comparable with those reported in previous r and omized trials , indicating that carefully monitored warfarin therapy can be used with reasonable safety in older patients BACKGROUND AND PURPOSE The risk of major vascular events after an initial episode of cerebral ischemia in patients with nonrheumatic atrial fibrillation ( NRAF ) varies from 2 % to 15 % in the first year and is approximately 5 % yearly thereafter . Few studies have reported on risk factors that can be used to identify high-risk subgroups within this patient population . METHODS We studied the predictive value of several easily obtainable clinical characteristics in a group of 375 placebo-treated patients with NRAF and a recent episode of transient or nondisabling cerebral ischemia who were entered in a multicenter clinical trial . The mean follow-up was 1.6 years . RESULTS By means of multivariate modeling , six independent variables were identified : history of previous thromboembolism , ischemic heart disease , enlarged cardiothoracic ratio on chest roentgenogram , systolic blood pressure greater than 160 mm Hg at study entry , NRAF for more than 1 year , and presence of an ischemic lesion on CT scan . These variables could also be used to stratify patients in low- , medium- , and high-risk subgroups for the other two arms of the trial , those treated with anticoagulation and aspirin .  Patients older than 75 years with three or more risk factors seemingly benefited less from both aspirin and anticoagulant treatment . CONCLUSIONS Easily obtainable patient characteristics are helpful in estimating the potential effect of adequate secondary prevention in patients with NRAF who recently suffered a transient ischemic attack or minor ischemic stroke 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 Oral anticoagulants ( OA ) are the drug of choice for stroke prevention in patients with non-rheumatic atrial fibrillation ( NRAF ) . This clear benefit/risk ratio comes from several r and omized clinical trials ( RCT ) in which highly selected patients were strictly monitored . The aim of this study was to ascertain whether the safety of OA was also obtained outside the setting of clinical trials in consecutive patients starting treatment and routinely followed at Italian anticoagulation clinics . A total of 433 patients with NRAF were enrolled in the ISCOAT study and followed up for a mean of 1.4 years . Two patients ( 0.3 % per year ) suffered from a complete non-fatal ischemic stroke , 8 patients ( 1.3 % per year ) died of thrombosis-related vascular death , and 11 patients ( 11 events , 1.8 % per year ) suffered from major bleedings ( 2 fatal ) . Major bleeding occurred more frequently in patients > 75 years of age ( 6 events , 5.1 % per year ) than in younger patients ( 5 events , 1.0 % per year ) . The cumulative incidence of major bleeding in patients over 75 years of age ( 10.8 % ; 95 % CI , 1.8 - 19.8 ) was significantly higher than in younger patients ( 2.8 % ; 95 % CI , 0.3 - 5.3 , p = 0.006 ) . Major primary bleeding unrelated to organic lesions ( 7 patients , 1 male and 6 females ) occurred in 5 elderly patients ( > 75 years old ) with a cumulative incidence ( 9.6 % ; 95 % CI 0.8 - 18.4 ) significantly higher than in younger patients ( 1.2 % ; 95 % CI , 0 - 3.0 , p = 0.0003 ) . Univariate analysis revealed a higher frequency of major primary bleeding in females , in diabetic patients and in in those who had suffered a previous thromboembolic event . Multivariate analysis revealed that only age grater than 75 years was independently related to major primary bleedings ( RR 6.6 ; 95 % CI 1.2 - 37 , p = 0.032 ) . Minor bleedings ( n = 27 ) were not more frequent in elderly patients ( 6 % vs 4 % per year , p = ns ) . Patients were kept at optimal intensity of treatment for 63 % of the time . These data confirm the efficacy of OA but identify elderly patients as a high risk group of major bleeding Context The appropriate level of warfarin anticoagulation in elderly patients with atrial fibrillation has been debated because of an age-associated increase in intracerebral hemorrhage . Contribution Patients with atrial fibrillation and intracerebral hemorrhage who were receiving anticoagulation were matched with similar patients who did not develop intracerebral hemorrhage . Although intracerebral hemorrhage was associated with increasing age ( especially > 85 years ) and increasing international normalized ratios ( INRs ) ( especially > 3.5 ) , the incidence of intracerebral hemorrhage was not statistically different in patients with INRs less than 2.0 and those with INRs between 2.0 and 3.0 . This was true even among those older than 75 years of age . Implication s Risk for intracerebral hemorrhage is not diminished in elderly patients with atrial fibrillation when anticoagulation is maintained below an INR of 2.0 . The Editors Intracranial hemorrhage is the most dangerous complication of warfarin anticoagulant therapy because of its high short-term risk for death and severe neurologic deficit ( 1 - 5 ) . Warfarin is extremely effective in reducing the risk for ischemic stroke associated with atrial fibrillation ( 6 , 7 ) . However , fear of hemorrhage may prompt some physicians to avoid prescribing anticoagulation ( 8) , especially in elderly patients , who appear to have a higher risk for hemorrhage ( 8 - 13 ) . Prominent recent guidelines recommend using lower-intensity anticoagulation for the primary prevention of stroke in patients older than 75 years of age who have atrial fibrillation ( 14 ) and suggest a target international normalized ratio ( INR ) range of 1.6 to 2.5 , despite evidence that the risk for ischemic stroke increases sharply at INRs less than 2.0 ( 15 , 16 ) . Previous studies have not thoroughly addressed the relationship of age and anticoagulation intensity to the risk for intracranial hemorrhage among patients with atrial fibrillation ( 1 , 2 ) . A study of 121 patients with warfarin-associated intracranial hemorrhage used the now-out date d prothrombin time ratio as a measure of anticoagulation intensity and did not specifically address risk in patients with atrial fibrillation ( 1 ) . Earlier studies also included patients receiving anticoagulation for mechanical valves , whose risk-to-benefit ratio is different from that of patients with atrial fibrillation ( 1 , 2 , 17 ) . As the number of individuals with atrial fibrillation increases ( 18 - 21 ) and as a greater proportion of older adults receive anticoagulant therapy ( 22 ) , more precise data are needed about the association of age , INR , and risk for intracranial hemorrhage . Intracranial hemorrhage , although critically important , is an uncommon complication among patients with atrial fibrillation who are receiving anticoagulation . As a result , r and omized trials and cohort studies have difficulty accumulating enough hemorrhage events to powerfully assess risk factors . To address these limitations , we performed a large casecontrol study to evaluate the relationship of increasing age and INR to the risk for intracranial hemorrhage among patients with nonvalvular atrial fibrillation . Methods Case- Patients We performed a casecontrol study comparing 2 groups : 1 ) case- patients with nonvalvular atrial fibrillation who developed intracranial hemorrhage while taking warfarin and 2 ) controls who were receiving anticoagulation for nonvalvular atrial fibrillation but did not develop intracranial hemorrhage . We found potential case- patients using the Partners HealthCare System Research Patient Data Registry , which can identify patients with specific International Classification of Diseases , Ninth Revision , Clinical Modification ( ICD-9-CM ) diagnoses by search ing the Massachusetts General Hospital billing system . We search ed for patients 18 years of age or older who had diagnoses of atrial fibrillation ( ICD-9-CM code 427.31 ) and intracranial hemorrhage ( ICD-9-CM codes 430 , 431 , 432.0 , 432.1 , 432.9 ) at any time from October 1993 to June 2002 . By 1993 , nearly all prothrombin time ratios at the hospital were reported as INRs . We review ed medical records to confirm whether patients were eligible , that is , whether they had intracranial hemorrhage documented by computed tomography or magnetic resonance imaging and documentation of warfarin therapy for atrial fibrillation at the time of the event . We excluded patients who were not taking warfarin at the time of hemorrhage ; those who were receiving anticoagulation for rheumatic heart disease , mitral stenosis , or mechanical valve placement ; those whose event was an ischemic stroke with hemorrhagic conversion ; or those in whom clinical factors may have led to hemorrhage independent of warfarin therapy . These factors included underlying anatomic brain abnormalities ( such as tumors or aneurysms ) , antecedent major head trauma ( skull fracture , trauma with loss of consciousness , motor vehicle injury , or neurosurgical procedures ) , or platelet count less than 50 109 cells/L. Starting in July 1994 , consecutive patients with intracerebral hemorrhage have been enrolled through the Massachusetts General Hospital emergency department as part of a longitudinal cohort study ( 23 ) . To vali date our automated search strategy , we compared our case-patient list with the list of patients identified through the cohort study and found that our search strategy missed only 4 patients with intracerebral hemorrhage . We obtained data on patient date of birth , sex , and ethnicity from computerized records . The type of hemorrhage ( intracerebral , subdural , subarachnoid , intraventricular , or epidural ) was determined through review of radiology reports . Data on presenting symptoms , history of minor head trauma , concomitant aspirin use , and disposition status were obtained from review of the admission medical record and were recorded on a st and ardized data collection form . We recorded the INR measurement obtained closest to the onset of symptoms . If an INR was not available or fresh frozen plasma or vitamin K was administered before the measurement , we considered INR data missing . We review ed medical charts for documentation of the following comorbid conditions : history of cerebrovascular disease ( defined as previous ischemic stroke or carotid artery disease ) , hypertension , congestive heart failure , coronary artery disease , diabetes mellitus , and cancer ( excluding nonmelanoma skin cancer ) . Controls Controls were sample d from patients managed by the Massachusetts General Hospital Anticoagulation Management Services clinic , which followed approximately 1000 patients receiving anticoagulation for atrial fibrillation at any given time during the study period . All patients who were followed in the anticoagulation clinic , received anticoagulation for atrial fibrillation , and had an INR measurement obtained in the same month and year as the given case date were assigned a r and om number . Six controls per case-patient were then r and omly selected . We matched case- patients to controls by INR date to account for any technical changes in INR testing that may have occurred over time . Because of this sampling method , an individual patient could potentially serve as a control for more than 1 case-patient ( 24 ) . Like case- patients , controls were 18 years of age or older ; were receiving anticoagulation for atrial fibrillation ; and had no documented rheumatic heart disease , mitral stenosis , or valve replacement . We sought data on potential confounders of the association of age , INR , and risk for intracranial hemorrhage , focusing on relevant comorbid conditions and combined use of aspirin with warfarin . We review ed available computerized discharge summaries , outpatient clinic notes , and medication lists from up to 2 years before the admission date . If combination warfarin and aspirin use was not documented , patients were considered to not be taking aspirin . Statistical Analysis Case- patients were categorized by type of hemorrhage : intracerebral , subdural , and other ( subarachnoid , intraventricular , or epidural ) . Clinical differences between types of hemorrhage were compared by using the KruskalWallis test for continuous variables ( age and INR ) and chi-square tests for categorical variables . We compared case- patients with controls by using multivariable conditional logistic regression , matching on INR date . Patient age was divided into 5-year intervals that were coded as indicator variables , and the odds of intracranial hemorrhage for each interval were compared with the odds of hemorrhage at a referent age of 70 to 74 years . The INR was divided into a set of ordered intervals that were coded as indicator variables . The relative odds for intracranial hemorrhage at each interval were calculated by using an INR of 2.0 to 3.0 as the referent category . In addition to age , INR , sex , and ethnicity , the following variables were included in the multivariable models to control for potential confounding effects of clinical factors and aspirin use : cerebrovascular disease , hypertension , congestive heart failure , coronary artery disease , diabetes mellitus , cancer , and concomitant aspirin use . If no records were available for review , comorbid conditions and aspirin use were coded as missing . We used multiple imputations for missing data on ethnicity , comorbid conditions , and aspirin use ( 25 ) . We tested for interactions between age and INR and comorbid conditions using 2-way interactions . None of the interaction terms were included in the model if they were not statistically significant when tested collectively . We tested the model 's goodness of fit using the HosmerLemeshow method ( 26 ) . Because the hospital 's anticoagulation clinic did not follow some case- patients before the event , and since factors relating to differences in outpatient care and monitoring could have confounded our analyses , we repeated these analyses in the subgroup of case- patients managed by the anticoagulation clinic . These restricted analyses OBJECTIVES To determine the most cost-effective method of screening for  atrial fibrillation ( AF ) in the population aged 65 years and over , as well as its prevalence and incidence in this age group . Also to evaluate the relative cost-effectiveness of different methods of recording and interpreting the electrocardiogram ( ECG ) within a screening programme . DESIGN Multicentred r and omised controlled trial . Purpose fully selected general practice s were r and omly allocated to 25 intervention practice s and 25 control practice s. SETTING Fifty primary care centres across the West Midl and s , UK . PARTICIPANTS Patients aged 65 years and over . INTERVENTIONS GPs and practice nurses in 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 targeted screening of people at higher risk of AF and total population screening . MAIN OUTCOME MEASURES AF detection rates in systematic ally screened and opportunistically screened population s in the intervention practice s were compared with AF detection rate in 5000 patients in the control practice s. The screening period was 12 months . RESULTS Baseline prevalence of AF was 7.2 % , with a higher prevalence in males ( 7.8 % ) and patients aged 75 years and over ( 10.3 % ) . The control population demonstrated higher baseline prevalence ( 7.9 % ) than either the systematic ( 6.9 % ) or opportunistic ( 6.9 % ) intervention population . In the control population 47 new cases were detected ( incidence 1.04 % per year ) . In the opportunistic arm 243 patients without a baseline diagnosis of AF were found to have an irregular pulse , with 177 having an ECG , yielding 31 new cases ( incidence 0.69 % per year ) . A further 44 cases were detected outside the screening programme ( overall incidence 1.64 % per year ) . In the systematic arm 2357 patients had an ECG yielding 52 new cases ( incidence 1.1 % per year ) . Of these , 31 were detected by targeted screening and a further 21 by total population screening . A further 22 cases were detected outside the screening programme ( overall incidence 1.62 % per year ) . In terms of ECG interpretation , computerised decision support software ( CDSS ) gave a sensitivity of 87.3 % , a specificity of 99.1 % and a positive predictive value ( PPV ) of 89.5 % compared with the gold st and ard ( cardiologist reporting ) . GPs and practice nurses performed less well . The only difference in performance between intervention population s and controls was that practice nurses from the control arm performed less well than with intervention practice nurses on interpretation of limb-lead ( PPV 38.8 % versus 20.8 % ) and single-lead ( PPV 37.7 % versus 24.0 % ) ECGs . The within-trial economic evaluation results showed the lowest incremental cost to be for the opportunistic arm , with an incremental cost-effectiveness ratio of 337 pounds Sterling for each additional case detected compared to the control arm . Opportunistic screening dominated both more intensive screening strategies . Model-based analyses showed small differences in cost and quality -adjusted life-years for different methods and intensities of screening , but annual opportunistic screening result ed in the lowest number of ischaemic strokes and greatest proportion of cases of AF diagnosed . Probabilistic sensitivity results indicated that there was a probability of approximately 60 % that screening from the age of 65 years was cost-effective in both men and women . CONCLUSIONS The results of the study indicated that in terms of a screening programme for atrial fibrillation in patients 65 and over , the only strategy that improved on routine practice was opportunistic screening , model-based analyses indicated that there was a probability of approximately 60 % of annual opportunistic screening being cost effective . It is suggested that the following topics are worthy of further investigation : the effect of the implementation of a screening programme for AF on the uptake and maintenance of anticoagulation in patients aged 65 years and over ; an evaluation of the role of CDSS in the diagnosis of cardiac arrythmias ; the best method for routinely detecting paroxysmal AF ; ways of improving healthcare professionals ' performance in ECG interpretation ; development of a robust economic model to incorporate data on new therapeutic agents for use as thromboprophylactic agents for patients with AF , and an evaluation of the relative risk of stroke for patients with incident as opposed to prevalent AF OBJECTIVE The goal of this study was to investigate the complications and control of warfarin treatment in patients with nonvalvular atrial fibrillation ( NVAF ) newly referred to an outpatient anticoagulation clinic . METHODS This study included new patients with NVAF who were referred to an anticoagulation clinic for warfarin therapy over a recruitment period of 21 months . To reflect real-world clinical practice , patient selection for anticoagulation and patient management were left to the referring physicians , who were blinded to their patients ' participation in the study . Patients were interviewed in person at the first clinic visit and then by telephone every 4 to 6 weeks . They were question ed about any bleeding or thromboembolic events . RESULTS A total of 402 patients were included ( 100 % of all new referrals over 21 months ) . The mean ( SD ) age was 72.3 ( 10.3 ) years , and 224 ( 56 % ) patients were men . The mean ( SD ) international normalized ratio ( INR ) was 2.4 ( 0.31 ) . Patients were followed up for a mean ( SD ) of 19 ( 8.1 ) months ( range , 1.0 - 31.0 months ) . They spent a mean ( SD ) 66 % ( 18.3 ) of time in the target range of INR ( ie , 2.0 - 3.0 ) . Annual event rates were 1.7 % ( 95 % CI , 0.4%-3.0 % ) for major bleeding , 16.6 % ( 95 % CI , 13.0%-20.2 % ) for minor bleeding , 1.2 % ( 95 % CI , 0.1%-2.3 % ) for ischemic stroke , and 0.3 % ( 95 % CI , 0.2%-0.8 % ) for transient ischemic attacks . There were no cases of hemorrhagic stroke or fatal bleeding . Variability of INR and number of medications were identified as risk factors for bleeding ( P = 0.03 and P = 0.001 , respectively ) . There was no significant association between age and bleeding . CONCLUSIONS Based on this analysis , the risks of long-term oral anticoagulation therapy in an outpatient anticoagulation clinic appear to reflect the results of clinical trials . Rates of ischemic stroke , major bleeding , and anticoagulation control were comparable . There was no age-related risk of complications
target: Some of the risk factors for anticoagulation-related bleeding are also indications for the use of anticoagulants in AF patients .
background: Atrial fibrillation ( AF ) is associated with an increased stroke risk that may be reduced by therapeutic anticoagulation .
  However , anticoagulation is associated with an increased risk of bleeding that in some patients may outweigh the benefits in reducing the risk of stroke .