human
***TASK*** the task is to summarize an input biomedical literature in six sentences 
    ***INPUT*** the input is a biomedical literature 
    ***OUTPUT*** the output is the summary of an input biomedical literature in six sentences 
    ***DOCUMENTATION*** 
    ***EXAMPLES*** 
    Input: 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  
    Output:
    
agent
Some of the risk factors for anticoagulation-related bleeding are also indications for the use of anticoagulants in AF patients .
***TASK*** the task is to summarize an input biomedical literature in six sentences 
    ***INPUT*** the input is a biomedical literature 
    ***OUTPUT*** the output is the summary of an input biomedical literature in six sentences 
    ***DOCUMENTATION*** 
    ***EXAMPLES*** 
    Input: 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  
    Output:
    