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: Stroke associated with atrial fibrillation ( AF ) is mainly due to embolism of thrombus formed during stasis of blood in the left atrial appendage ( LAA ) . Pathophysiologic correlates of appendage flow velocity as assessed by transesophageal echocardiography ( TEE ) in patients with AF have not been defined . To evaluate the hypothesis that reduced velocity is associated with spontaneous echocardiographic contrast and thrombus in the LAA and with clinical embolic events , we measured LAA flow velocity by TEE in 721 patients with nonvalvular AF entering the Stroke Prevention in Atrial Fibrillation ( SPAF-III ) study . Patient features , TEE findings , and subsequent cardioembolic events were correlated with velocity by multivariate analysis . Patients in AF during TEE displayed lower peak ante grade ( emptying ) flow velocity ( Anu(p ) ) than those with intermittent AF in sinus rhythm during TEE ( 33 cm/s vs 61 cm/s , respectively , P < .0001 ) . Anu(p ) < 20 cm/s was associated with dense spontaneous echocardiographic contrast ( P < .001 ) , appendage thrombus ( P < .01 ) , and subsequent cardioembolic events ( P < .01 ) . Independent predictors of Anu(p ) < 20 cm/s included age ( P = .009 ) , systolic blood pressure ( P < .001 ) , sustained AF ( P = .01 ) , ischemic heart disease ( P = .01 ) , and left atrial area ( P = .04 ) . Multivariate analysis found both Anu(p ) < 20 cm/s ( relative risk 2.6 , P = .02 ) and clinical risk factors ( relative risk 3.3 , P = .002 ) independently associated with LAA thrombus . LAA Anu(p ) is reduced in AF and associated with spontaneous echocardiographic contrast , appendage thrombus , and cardioembolic stroke . Systolic hypertension and aortic atherosclerosis , independent clinical predictors of stroke in patients with AF , also correlated with LAA Anu(p ) . Our results support the role of reduced LAA Anu(p ) in the generation of stasis , thrombus formation , and embolism in patients with AF , although other mechanisms also contribute to stroke Stroke incidence in Copenhagen , Denmark was recorded in a r and om population sample of 19,327 persons invited for two health examinations with 5 years ' interval from 1976 to 1983 . Stroke incidence increased exponentially with age . After adjustment to the age and sex distribution of the Danish population in 1980 , the estimated incidence of first stroke was 1.41/1000 women and 2.48/1000 men ; the total incidence was 1.94/1000 population . Risk factor analysis was based on the initial examination of 13,088 persons greater than 35 years old without previous stroke who responded to the first invitation , in whom 295 first strokes were subsequently observed . We used the regression model of Cox . However , our use of this model differs from the somewhat automatic procedures normally used to develop prognostic models . Evaluation of the causative effect of a particular risk factor requires that the direction of mutual influences between the factor in question and other risk factors is established/postulated . Among the 16 potential risk factors for stroke we examined , significant effects were found for age , sex , household income , smoking habits , systolic blood pressure , diabetes , plasma cholesterol concentration , ischemic heart disease , and atrial fibrillation . No significant effect could be demonstrated for a positive family history of stroke , years of school education , marital status , alcohol consumption , daily use of tranquilizers , body mass index , or postmenopausal hormone treatment 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 Background and Purpose — Long-term anticoagulation is routinely used for secondary stroke prevention in atrial fibrillation , often regardless of stroke subtype . Although the role of warfarin in cardioembolic stroke is established , it may not prevent recurrence in other stroke subtypes , even in the presence of atrial fibrillation . Methods — This was a 2-year , prospect i ve , intervention study conducted in a district general hospital . Participants included 386 acute stroke patients with atrial fibrillation . Subjects were characterized for stroke subtype on clinical , neuroimaging , carotid ultrasonographic , and echocardiographic criteria . Eligible patients were treated with adjusted-dose warfarin ( international normalized ratio , 2.0 to 3.0 ) . Aspirin ( 75 to 300 mg/d ) was used in patients with contraindications or those who refused anticoagulation . The main outcome measures were rate of recurrent stroke by subtype and major and minor bleeding complications . Results — The  aspirin group ( n=172 ) was comparable to the  warfarin group ( n=214 ) in terms of age , sex , risk factors , and initial stroke subtype . The rate of recurrent stroke was higher ( 9.5 % versus 4.9 % , P < 0.02 ) but that of major bleeding was lower ( 0.6 % versus 2.5 % , P < 0.05 ) with aspirin . The increased stroke rate with aspirin was due predominantly to cardioembolic recurrence in patients presenting initially with cardioembolic stroke ( 8.4 % versus 1.9 % , P < 0.01 ) . The recurrence rate in aspirin-treated patients who presented with lacunar stroke and atrial fibrillation was similar to that seen in patients receiving warfarin ( 8.8 % versus 8.9 % ) . Conclusions — In this cohort of stroke patients with atrial fibrillation , anticoagulation was superior to aspirin in preventing cardioembolic but not lacunar recurrence . Determination of stroke subtype may be important in anticoagulation decisions for secondary prevention , and further studies are required Background Atrial fibrillation in the absence of rheumatic valvular disease is associated with a fivefold to sevenfold increased risk of ischemic stroke . Methods and Main Results . The Stroke Prevention in Atrial Fibrillation Study , a multicenter , r and omized trial , compared 325 mg/day aspirin ( double-blind ) or warfarin with placebo for prevention of ischemic stroke and systemic embolism ( primary events ) , and included 1,330 in patients and out patients with constant or intermittent atrial fibrillation . During a mean follow-up of 1.3 years , the rate of primary events in patients assigned to placebo was 6.3 % per year and was reduced by 42 % in those assigned to aspirin ( 3.6 % per year , p = 0.02 ; 95 % confidence interval , 9–63 % ) . In the subgroup of  warfarin-eligible patients ( most less than 76 years old ) , warfarin dose-adjusted to prolong prothrombin time to 1.3-fold to 1.8-fold that of control reduced the risk of primary events by 67 % ( warfarin versus placebo , 2.3 % versus 7.4 % per year , p = 0.01 ; 95 % confidence interval , 27–85 % ) . Primary events or death were reduced 58 % ( p = 0.01 ) by warfarin and 32 % ( p = 0.02 ) by aspirin . The risk of significant bleeding was 1.5 % , 1.4 % , and 1.6%o per year in patients assigned to warfarin , aspirin , and placebo , respectively . Conclusions Aspirin and warfarin are both effective in reducing ischemic stroke and systemic embolism in patients with atrial fibrillation . Because warfarin-eligible patients composed a subset of all aspirin-eligible patients , the magnitude of reduction in events by warfarin versus aspirin can not be compared . Too few events occurred in warfarin-eligible patients to directly assess the relative benefit of aspirin compared with warfarin , and the trial is continuing to address this issue . Patients with nonrheumatic atrial fibrillation who can safely take either aspirin or warfarin should receive prophylactic antithrombotic therapy to reduce the risk of stroke BACKGROUND Atherosclerotic intracranial arterial stenosis is an important cause of stroke . Warfarin is commonly used in preference to aspirin for this disorder , but these therapies have not been compared in a r and omized trial . METHODS We r and omly assigned patients with transient ischemic attack or stroke caused by angiographically verified 50 to 99 percent stenosis of a major intracranial artery to receive warfarin ( target international normalized ratio , 2.0 to 3.0 ) or aspirin ( 1300 mg per day ) in a double-blind , multicenter clinical trial . The primary end point was ischemic stroke , brain hemorrhage , or death from vascular causes other than stroke . RESULTS After 569 patients had undergone r and omization , enrollment was stopped because of concerns about the safety of the patients who had been assigned to receive warfarin .  During a mean follow-up period of 1.8 years , adverse events in the two groups included death ( 4.3 percent in the aspirin group vs. 9.7 percent in the warfarin group ; hazard ratio for aspirin relative to warfarin , 0.46 ; 95 percent confidence interval , 0.23 to 0.90 ; P=0.02 ) , major hemorrhage ( 3.2 percent vs. 8.3 percent , respectively ; hazard ratio , 0.39 ; 95 percent confidence interval , 0.18 to 0.84 ; P=0.01 ) , and myocardial infa rct ion or sudden death ( 2.9 percent vs. 7.3 percent , respectively ; hazard ratio , 0.40 ; 95 percent confidence interval , 0.18 to 0.91 ; P=0.02 ) . The rate of death from vascular causes was 3.2 percent in the aspirin group and 5.9 percent in the warfarin group ( P=0.16 ) ; the rate of death from nonvascular causes was 1.1 percent and 3.8 percent , respectively ( P=0.05 ) . The primary end point occurred in 22.1 percent of the patients in the aspirin group and 21.8 percent of those in the warfarin group ( hazard ratio , 1.04 ; 95 percent confidence interval , 0.73 to 1.48 ; P=0.83 ) . CONCLUSIONS Warfarin was associated with significantly higher rates of adverse events and provided no benefit over aspirin in this trial . Aspirin should be used in preference to warfarin for patients with intracranial arterial stenosis BACKGROUND AND PURPOSE Despite large r and omised trials that demonstrated the efficacy of oral anticoagulants in the primary and secondary prevention of stroke in patients with non-valvular atrial fibrillation ( AF ) , anticoagulation therapy remains largely under-used in older patients , who are at risk of first ever or recurrent stroke . The aim of the present study was to assess the influence of anticoagulation therapy on long-term prognosis in the oldest old stroke patients with AF after adjusting for baseline risk factors . METHODS We evaluated prospect ively a consecutive series of 207 older people ( > 75 years ) with AF and first ever ischaemic stroke . During the follow-up period ( mean 88.4 months , range 3 - 120 ) , the study population was under either oral 
    Output:
    
agent
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 .
***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: Stroke associated with atrial fibrillation ( AF ) is mainly due to embolism of thrombus formed during stasis of blood in the left atrial appendage ( LAA ) . Pathophysiologic correlates of appendage flow velocity as assessed by transesophageal echocardiography ( TEE ) in patients with AF have not been defined . To evaluate the hypothesis that reduced velocity is associated with spontaneous echocardiographic contrast and thrombus in the LAA and with clinical embolic events , we measured LAA flow velocity by TEE in 721 patients with nonvalvular AF entering the Stroke Prevention in Atrial Fibrillation ( SPAF-III ) study . Patient features , TEE findings , and subsequent cardioembolic events were correlated with velocity by multivariate analysis . Patients in AF during TEE displayed lower peak ante grade ( emptying ) flow velocity ( Anu(p ) ) than those with intermittent AF in sinus rhythm during TEE ( 33 cm/s vs 61 cm/s , respectively , P < .0001 ) . Anu(p ) < 20 cm/s was associated with dense spontaneous echocardiographic contrast ( P < .001 ) , appendage thrombus ( P < .01 ) , and subsequent cardioembolic events ( P < .01 ) . Independent predictors of Anu(p ) < 20 cm/s included age ( P = .009 ) , systolic blood pressure ( P < .001 ) , sustained AF ( P = .01 ) , ischemic heart disease ( P = .01 ) , and left atrial area ( P = .04 ) . Multivariate analysis found both Anu(p ) < 20 cm/s ( relative risk 2.6 , P = .02 ) and clinical risk factors ( relative risk 3.3 , P = .002 ) independently associated with LAA thrombus . LAA Anu(p ) is reduced in AF and associated with spontaneous echocardiographic contrast , appendage thrombus , and cardioembolic stroke . Systolic hypertension and aortic atherosclerosis , independent clinical predictors of stroke in patients with AF , also correlated with LAA Anu(p ) . Our results support the role of reduced LAA Anu(p ) in the generation of stasis , thrombus formation , and embolism in patients with AF , although other mechanisms also contribute to stroke Stroke incidence in Copenhagen , Denmark was recorded in a r and om population sample of 19,327 persons invited for two health examinations with 5 years ' interval from 1976 to 1983 . Stroke incidence increased exponentially with age . After adjustment to the age and sex distribution of the Danish population in 1980 , the estimated incidence of first stroke was 1.41/1000 women and 2.48/1000 men ; the total incidence was 1.94/1000 population . Risk factor analysis was based on the initial examination of 13,088 persons greater than 35 years old without previous stroke who responded to the first invitation , in whom 295 first strokes were subsequently observed . We used the regression model of Cox . However , our use of this model differs from the somewhat automatic procedures normally used to develop prognostic models . Evaluation of the causative effect of a particular risk factor requires that the direction of mutual influences between the factor in question and other risk factors is established/postulated . Among the 16 potential risk factors for stroke we examined , significant effects were found for age , sex , household income , smoking habits , systolic blood pressure , diabetes , plasma cholesterol concentration , ischemic heart disease , and atrial fibrillation . No significant effect could be demonstrated for a positive family history of stroke , years of school education , marital status , alcohol consumption , daily use of tranquilizers , body mass index , or postmenopausal hormone treatment 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 Background and Purpose — Long-term anticoagulation is routinely used for secondary stroke prevention in atrial fibrillation , often regardless of stroke subtype . Although the role of warfarin in cardioembolic stroke is established , it may not prevent recurrence in other stroke subtypes , even in the presence of atrial fibrillation . Methods — This was a 2-year , prospect i ve , intervention study conducted in a district general hospital . Participants included 386 acute stroke patients with atrial fibrillation . Subjects were characterized for stroke subtype on clinical , neuroimaging , carotid ultrasonographic , and echocardiographic criteria . Eligible patients were treated with adjusted-dose warfarin ( international normalized ratio , 2.0 to 3.0 ) . Aspirin ( 75 to 300 mg/d ) was used in patients with contraindications or those who refused anticoagulation . The main outcome measures were rate of recurrent stroke by subtype and major and minor bleeding complications . Results — The  aspirin group ( n=172 ) was comparable to the  warfarin group ( n=214 ) in terms of age , sex , risk factors , and initial stroke subtype . The rate of recurrent stroke was higher ( 9.5 % versus 4.9 % , P < 0.02 ) but that of major bleeding was lower ( 0.6 % versus 2.5 % , P < 0.05 ) with aspirin . The increased stroke rate with aspirin was due predominantly to cardioembolic recurrence in patients presenting initially with cardioembolic stroke ( 8.4 % versus 1.9 % , P < 0.01 ) . The recurrence rate in aspirin-treated patients who presented with lacunar stroke and atrial fibrillation was similar to that seen in patients receiving warfarin ( 8.8 % versus 8.9 % ) . Conclusions — In this cohort of stroke patients with atrial fibrillation , anticoagulation was superior to aspirin in preventing cardioembolic but not lacunar recurrence . Determination of stroke subtype may be important in anticoagulation decisions for secondary prevention , and further studies are required Background Atrial fibrillation in the absence of rheumatic valvular disease is associated with a fivefold to sevenfold increased risk of ischemic stroke . Methods and Main Results . The Stroke Prevention in Atrial Fibrillation Study , a multicenter , r and omized trial , compared 325 mg/day aspirin ( double-blind ) or warfarin with placebo for prevention of ischemic stroke and systemic embolism ( primary events ) , and included 1,330 in patients and out patients with constant or intermittent atrial fibrillation . During a mean follow-up of 1.3 years , the rate of primary events in patients assigned to placebo was 6.3 % per year and was reduced by 42 % in those assigned to aspirin ( 3.6 % per year , p = 0.02 ; 95 % confidence interval , 9–63 % ) . In the subgroup of  warfarin-eligible patients ( most less than 76 years old ) , warfarin dose-adjusted to prolong prothrombin time to 1.3-fold to 1.8-fold that of control reduced the risk of primary events by 67 % ( warfarin versus placebo , 2.3 % versus 7.4 % per year , p = 0.01 ; 95 % confidence interval , 27–85 % ) . Primary events or death were reduced 58 % ( p = 0.01 ) by warfarin and 32 % ( p = 0.02 ) by aspirin . The risk of significant bleeding was 1.5 % , 1.4 % , and 1.6%o per year in patients assigned to warfarin , aspirin , and placebo , respectively . Conclusions Aspirin and warfarin are both effective in reducing ischemic stroke and systemic embolism in patients with atrial fibrillation . Because warfarin-eligible patients composed a subset of all aspirin-eligible patients , the magnitude of reduction in events by warfarin versus aspirin can not be compared . Too few events occurred in warfarin-eligible patients to directly assess the relative benefit of aspirin compared with warfarin , and the trial is continuing to address this issue . Patients with nonrheumatic atrial fibrillation who can safely take either aspirin or warfarin should receive prophylactic antithrombotic therapy to reduce the risk of stroke BACKGROUND Atherosclerotic intracranial arterial stenosis is an important cause of stroke . Warfarin is commonly used in preference to aspirin for this disorder , but these therapies have not been compared in a r and omized trial . METHODS We r and omly assigned patients with transient ischemic attack or stroke caused by angiographically verified 50 to 99 percent stenosis of a major intracranial artery to receive warfarin ( target international normalized ratio , 2.0 to 3.0 ) or aspirin ( 1300 mg per day ) in a double-blind , multicenter clinical trial . The primary end point was ischemic stroke , brain hemorrhage , or death from vascular causes other than stroke . RESULTS After 569 patients had undergone r and omization , enrollment was stopped because of concerns about the safety of the patients who had been assigned to receive warfarin .  During a mean follow-up period of 1.8 years , adverse events in the two groups included death ( 4.3 percent in the aspirin group vs. 9.7 percent in the warfarin group ; hazard ratio for aspirin relative to warfarin , 0.46 ; 95 percent confidence interval , 0.23 to 0.90 ; P=0.02 ) , major hemorrhage ( 3.2 percent vs. 8.3 percent , respectively ; hazard ratio , 0.39 ; 95 percent confidence interval , 0.18 to 0.84 ; P=0.01 ) , and myocardial infa rct ion or sudden death ( 2.9 percent vs. 7.3 percent , respectively ; hazard ratio , 0.40 ; 95 percent confidence interval , 0.18 to 0.91 ; P=0.02 ) . The rate of death from vascular causes was 3.2 percent in the aspirin group and 5.9 percent in the warfarin group ( P=0.16 ) ; the rate of death from nonvascular causes was 1.1 percent and 3.8 percent , respectively ( P=0.05 ) . The primary end point occurred in 22.1 percent of the patients in the aspirin group and 21.8 percent of those in the warfarin group ( hazard ratio , 1.04 ; 95 percent confidence interval , 0.73 to 1.48 ; P=0.83 ) . CONCLUSIONS Warfarin was associated with significantly higher rates of adverse events and provided no benefit over aspirin in this trial . Aspirin should be used in preference to warfarin for patients with intracranial arterial stenosis BACKGROUND AND PURPOSE Despite large r and omised trials that demonstrated the efficacy of oral anticoagulants in the primary and secondary prevention of stroke in patients with non-valvular atrial fibrillation ( AF ) , anticoagulation therapy remains largely under-used in older patients , who are at risk of first ever or recurrent stroke . The aim of the present study was to assess the influence of anticoagulation therapy on long-term prognosis in the oldest old stroke patients with AF after adjusting for baseline risk factors . METHODS We evaluated prospect ively a consecutive series of 207 older people ( > 75 years ) with AF and first ever ischaemic stroke . During the follow-up period ( mean 88.4 months , range 3 - 120 ) , the study population was under either oral 
    Output:
    