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: Aim Anticoagulation prophylaxis for stroke is recommended for at-risk patients with either persistent or paroxysmal atrial fibrillation ( AF ) . We compared outcomes in patients with persistent vs. paroxysmal AF receiving oral anticoagulation . Methods and results Patients r and omized in the Rivaroxaban Once Daily Oral Direct Factor Xa Inhibition Compared With Vitamin K Antagonism for Prevention of Stroke and Embolism Trial in Atrial Fibrillation ( ROCKET-AF ) trial ( n = 14 264 ) were grouped by baseline AF category : paroxysmal or persistent . Multivariable adjustment was performed to compare thrombo-embolic events , bleeding , and death between groups , in high-risk subgroups , and across treatment assignment ( rivaroxaban or warfarin ) . Of 14 062 patients , 11 548 ( 82 % ) had persistent AF and 2514 ( 18 % ) had paroxysmal AF . Patients with persistent AF were marginally older ( 73 vs. 72 , P = 0.03 ) , less likely female ( 39 vs. 45 % , P < 0.0001 ) , and more likely to have previously used vitamin K antagonists ( 64 vs. 56 % , P < 0.0001 ) compared with patients with paroxysmal AF . In patients r and omized to warfarin , time in therapeutic range was similar ( 58 vs. 57 % , P = 0.94 ) . Patients with persistent AF had higher adjusted rates of stroke or systemic embolism ( 2.18 vs. 1.73 events per 100-patient-years , P = 0.048 ) and all-cause mortality ( 4.78 vs. 3.52 , P = 0.006 ) . Rates of major bleeding were similar ( 3.55 vs. 3.31 , P = 0.77 ) . Rates of stroke or systemic embolism in both types of AF did not differ by treatment assignment ( rivaroxaban vs. warfarin , Pinteraction = 0.6 ) . Conclusion In patients with AF at moderate-to-high risk of stroke receiving anticoagulation , those with persistent AF have a higher risk of thrombo-embolic events and worse survival compared with paroxysmal AF Background and Purpose — We sought to investigate the apparently high risk of early death after an ischemic stroke among patients with atrial fibrillation ( AF ) , identify the main factors associated with early death , and assess the effect of treatment with different doses of subcutaneous unfractionated heparin ( UFH ) given within 48 hours . Methods — We studied the occurrence of major clinical events within 14 days among 18 451 patients from the International Stroke Trial , first for all treatment groups combined . Then , among patients with AF , we examined the effects of treatment with subcutaneous UFH started within 48 hours and continued until 14 days after stroke onset . Results — A total of 3169 patients ( 17 % ) had AF . Seven hundred eighty-four patients were allocated to UFH 12 500 IU SC BID , 773 to UFH 5000 IU SC BID , and 1612 to no heparin . Within each of these groups , half of the patients were r and omly assigned to aspirin 300 mg once daily . Compared with patients without AF , patients with AF were more likely to be female ( 56 % versus 45 % ) , to be old ( mean age , 78 versus 71 years ) , to have an infa rct on prer and omization CT ( 57 % versus 47 % ) , and to have impaired consciousness ( 37 % versus 20 % ) . The initial ischemic stroke type was more often a large-artery infa rct ( 36 % versus 21 % ) . A lacunar stroke syndrome was less common ( 13 % versus 26 % ) . Death within 14 days was more common in patients with AF ( 17 % versus 8 % ) and more often attributed to neurological damage from the initial stroke ( 10 % versus 4 % ) . The frequency of recurrent ischemic or undefined stroke was not significantly different ( 3.9 % versus 3.3 % ) . The proportion of AF patients with further events within 14 days allocated to UFH 12 500 IU ( n=784 ) , UFH 5000 IU ( n=773 ) , and to no-heparin ( n=1612 ) groups were as follows : ischemic stroke , 2.3 % , 3.4 % , 4.9 % ( P = 0.001 ) ; hemorrhagic stroke , 2.8 % , 1.3 % , 0.4 % ( P < 0.0001 ) ; and any stroke or death , 18.8 % , 19.4 % and 20.7 % ( P = 0.3 ) , respectively . No effect of heparin on the proportion of patients dead or dependent at 6 months was apparent . Conclusions — Acute ischemic stroke patients with AF have a higher risk of early death , which can be explained by older age and larger infa rcts but not by a higher risk of early recurrent ischemic stroke , although slightly more patients with AF died from a fatal recurrent stroke of ischemic or unknown type ( 1.3 % versus 0.9 % ) . In patients with AF the absolute risk of early recurrent stroke is low , and there is no net advantage to treatment with heparin . These data do not support the widespread use of intensive heparin regimens in the acute phase of ischemic stroke associated with AF BACKGROUND Few epidemiologic cohort studies have evaluated atrial flutter ( flutter ) as an arrhythmia distinct from atrial fibrillation ( AF ) . OBJECTIVE The purpose of this study was to examine the clinical correlates of flutter and its associated outcomes to distinguish them from those associated with AF in the Framingham Heart Study . METHODS We review ed  and adjudicated electrocardiograms ( ECGs ) previously classified as flutter or AF/flutter and another 100 ECGs r and omly selected from AF cases . We examined the clinical correlates of flutter by matching up to 5 AF and 5 referents to each flutter case using a nested case referent design . We determined the 10-year outcomes associated with flutter with Cox models . RESULTS During mean follow-up of 33.0 ± 12.2 years , 112 participants ( mean age 72 ± 10 years , 30 % women ) developed flutter . In multivariable analyses , smoking ( odds ratio [ OR ] 2.84 , 95 % confidence interval [ CI ] 1.54 - 5.23 ) , increased PR interval ( OR 1.28 per SD , 95 % CI 1.03 - 1.60 ) , myocardial infa rct ion ( OR 2.25 , 95 % CI 1.05 - 4.80 ) and heart failure ( OR 5.22 , 95 % CI 1.26 - 21.64 ) were associated with incident flutter . In age- and sex-adjusted models , flutter ( vs referents ) was associated with 10-year increased risk of AF ( hazard ratio [ HR ] 5.01 , 95 % CI 3.14 - 7.99 ) , myocardial infa rct ion ( HR 3.05 , 95 % CI 1.42 - 6.59 ) , heart failure ( HR 4.14 , 95 % CI 1.90 - 8.99 ) , stroke ( HR 2.17 , 95 % CI 1.13 - 4.17 ) , and mortality ( HR 2.00 , 95 % CI 1.44 - 2.79 ) . CONCLUSION We identified the clinical correlates associated with flutter and observed that flutter was associated with multiple adverse outcomes Background — Atrial fibrillation is associated with increased mortality , but the specific causes of death and their predictors have not been described among patients on effective anticoagulant therapy . Methods and Results — The R and omized Evaluation of Long-Term Anticoagulant Therapy ( RE-LY ) trial r and omized 18 113 patients ( age , 71.5±9 years ; male , 64 % ; CHADS2 score , 2.1±1 ) to receive dabigatran or warfarin .  Median follow-up was 2 years , and complete follow-up was achieved in 99.9 % of patients . All deaths were categorized by the investigators using prespecified definitions followed by central adjudication . Overall , 1371 deaths occurred ( annual mortality rate , 3.84 % ; 95 % confidence interval [ CI ] , 3.64–4.05 ) . Cardiac deaths ( sudden cardiac death and progressive heart failure ) accounted for 37.4 % of all deaths , whereas stroke- and hemorrhage-related deaths represented 9.8 % of the total mortality . An examination of the causes of death according to dabigatran or warfarin showed that dabigatran significantly reduced vascular ( embolism and hemorrhage-related ) mortality ( relative risk , 0.63 ; 95 % CI , 0.45–0.88 ; P=0.007 ) , whereas other causes of death were similar between treatments , including cardiac mortality ( relative risk , 0.96 ; 95 % CI , 0.80–1.15 ; P=0.638 ) . The two strongest independent predictors of cardiac death in this population were heart failure ( hazard ratio , 3.02 ; 95 % CI , 2.45–3.73 ; P<0.0001 ) , and prior myocardial infa rct ion ( hazard ratio , 2.05 ; 95 % CI , 1.61–2.62 ; P<0.0001 ) . Conclusions — The majority of deaths are not related to stroke in a contemporary anticoagulated atrial fibrillation population . These results emphasize the need to identify interventions beyond effective anticoagulation to further reduce mortality in atrial fibrillation . Clinical Trial Registration — URL : http://www . clinical trials.gov . Unique identifier : NCT00262600 Background — There is a modest risk of myocardial infa rct ion ( MI )  and myocardial ischemic events in patients with atrial fibrillation . Methods and Results — Data from the RE-LY study ( R and omized Evaluation of Long-Term Anticoagulation Therapy ) were used to report rates of MI , unstable angina , cardiac arrest , and cardiac death and the prespecified net clinical benefit and treatment effects of dabigatran versus warfarin .  MI occurred at annual rates of 0.82 % and 0.81 % with dabigatran 110 or 150 mg BID compared with 0.64 % with warfarin ( hazard ratio [ HR ] 1.29 , 95 % confidence interval [ CI ] 0.96–1.75 , P=0.09 for dabigatran 110 mg ; HR 1.27 , 95 % CI 0.94–1.71 , P=0.12 for dabigatran 150 mg ) . Annual rates of a composite of MI , unstable angina , cardiac arrest , and cardiac death were 3.16 % per year with dabigatran 110 mg , 3.33 % per year with dabigatran 150 mg , and 3.41 % per year with warfarin ( HR versus warfarin 0.93 , 95 % CI 0.80–1.06 , P=0.28 for dabigatran 110 mg and HR 0.98 , 95 % CI 0.85–1.12 , P=0.77 for dabigatran 150 mg ) . Events prespecified as “ net clinical benefit ” ( all strokes , systemic embolism , MI , pulmonary embolism , major bleeding , and all-cause death ) occurred at a rate of 7.34 % per year with dabigatran 110 mg , 7.11 % per year with dabigatran 150 mg , and 7.91 % per year with warfarin ( HR 0.92 , 95 % CI 0.84–1.01 , P=0.09 for dabigatran 110 mg and HR 0.90 , 95 % CI 0.82–0.99 , P=0.02 for dabigatran 150 mg ) . The relative effects of dabigatran versus warfarin on myocardial ischemic events were consistent in patients with or without a baseline history of MI or coronary artery disease . Conclusions — There was a nonsignificant increase in MI with dabigatran compared with warfarin , but other myocardial ischemic events were not increased . Treatment effects of dabigatran were consistent in patients at higher and lower risk of myocardial ischemic events . Clinical Trial Registration — URL : http://www . clinical trials.gov . Unique identifier : NCT 00262600 BACKGROUND AND PURPOSE Thoracic aortic plaque identified by transesophageal echocardiography heightens the risk of stroke associated with atrial fibrillation ( AF ) . We sought to identify the prevalence , predictors , and implication s of aortic plaque in patients with nonvalvular AF . METHODS Thoracic aortic plaque was prospect ively sought in 770 persons with AF with 
    Output:
    
agent
These results showed that AF is an independent risk factor for MI , CV death , and CV events
***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: Aim Anticoagulation prophylaxis for stroke is recommended for at-risk patients with either persistent or paroxysmal atrial fibrillation ( AF ) . We compared outcomes in patients with persistent vs. paroxysmal AF receiving oral anticoagulation . Methods and results Patients r and omized in the Rivaroxaban Once Daily Oral Direct Factor Xa Inhibition Compared With Vitamin K Antagonism for Prevention of Stroke and Embolism Trial in Atrial Fibrillation ( ROCKET-AF ) trial ( n = 14 264 ) were grouped by baseline AF category : paroxysmal or persistent . Multivariable adjustment was performed to compare thrombo-embolic events , bleeding , and death between groups , in high-risk subgroups , and across treatment assignment ( rivaroxaban or warfarin ) . Of 14 062 patients , 11 548 ( 82 % ) had persistent AF and 2514 ( 18 % ) had paroxysmal AF . Patients with persistent AF were marginally older ( 73 vs. 72 , P = 0.03 ) , less likely female ( 39 vs. 45 % , P < 0.0001 ) , and more likely to have previously used vitamin K antagonists ( 64 vs. 56 % , P < 0.0001 ) compared with patients with paroxysmal AF . In patients r and omized to warfarin , time in therapeutic range was similar ( 58 vs. 57 % , P = 0.94 ) . Patients with persistent AF had higher adjusted rates of stroke or systemic embolism ( 2.18 vs. 1.73 events per 100-patient-years , P = 0.048 ) and all-cause mortality ( 4.78 vs. 3.52 , P = 0.006 ) . Rates of major bleeding were similar ( 3.55 vs. 3.31 , P = 0.77 ) . Rates of stroke or systemic embolism in both types of AF did not differ by treatment assignment ( rivaroxaban vs. warfarin , Pinteraction = 0.6 ) . Conclusion In patients with AF at moderate-to-high risk of stroke receiving anticoagulation , those with persistent AF have a higher risk of thrombo-embolic events and worse survival compared with paroxysmal AF Background and Purpose — We sought to investigate the apparently high risk of early death after an ischemic stroke among patients with atrial fibrillation ( AF ) , identify the main factors associated with early death , and assess the effect of treatment with different doses of subcutaneous unfractionated heparin ( UFH ) given within 48 hours . Methods — We studied the occurrence of major clinical events within 14 days among 18 451 patients from the International Stroke Trial , first for all treatment groups combined . Then , among patients with AF , we examined the effects of treatment with subcutaneous UFH started within 48 hours and continued until 14 days after stroke onset . Results — A total of 3169 patients ( 17 % ) had AF . Seven hundred eighty-four patients were allocated to UFH 12 500 IU SC BID , 773 to UFH 5000 IU SC BID , and 1612 to no heparin . Within each of these groups , half of the patients were r and omly assigned to aspirin 300 mg once daily . Compared with patients without AF , patients with AF were more likely to be female ( 56 % versus 45 % ) , to be old ( mean age , 78 versus 71 years ) , to have an infa rct on prer and omization CT ( 57 % versus 47 % ) , and to have impaired consciousness ( 37 % versus 20 % ) . The initial ischemic stroke type was more often a large-artery infa rct ( 36 % versus 21 % ) . A lacunar stroke syndrome was less common ( 13 % versus 26 % ) . Death within 14 days was more common in patients with AF ( 17 % versus 8 % ) and more often attributed to neurological damage from the initial stroke ( 10 % versus 4 % ) . The frequency of recurrent ischemic or undefined stroke was not significantly different ( 3.9 % versus 3.3 % ) . The proportion of AF patients with further events within 14 days allocated to UFH 12 500 IU ( n=784 ) , UFH 5000 IU ( n=773 ) , and to no-heparin ( n=1612 ) groups were as follows : ischemic stroke , 2.3 % , 3.4 % , 4.9 % ( P = 0.001 ) ; hemorrhagic stroke , 2.8 % , 1.3 % , 0.4 % ( P < 0.0001 ) ; and any stroke or death , 18.8 % , 19.4 % and 20.7 % ( P = 0.3 ) , respectively . No effect of heparin on the proportion of patients dead or dependent at 6 months was apparent . Conclusions — Acute ischemic stroke patients with AF have a higher risk of early death , which can be explained by older age and larger infa rcts but not by a higher risk of early recurrent ischemic stroke , although slightly more patients with AF died from a fatal recurrent stroke of ischemic or unknown type ( 1.3 % versus 0.9 % ) . In patients with AF the absolute risk of early recurrent stroke is low , and there is no net advantage to treatment with heparin . These data do not support the widespread use of intensive heparin regimens in the acute phase of ischemic stroke associated with AF BACKGROUND Few epidemiologic cohort studies have evaluated atrial flutter ( flutter ) as an arrhythmia distinct from atrial fibrillation ( AF ) . OBJECTIVE The purpose of this study was to examine the clinical correlates of flutter and its associated outcomes to distinguish them from those associated with AF in the Framingham Heart Study . METHODS We review ed  and adjudicated electrocardiograms ( ECGs ) previously classified as flutter or AF/flutter and another 100 ECGs r and omly selected from AF cases . We examined the clinical correlates of flutter by matching up to 5 AF and 5 referents to each flutter case using a nested case referent design . We determined the 10-year outcomes associated with flutter with Cox models . RESULTS During mean follow-up of 33.0 ± 12.2 years , 112 participants ( mean age 72 ± 10 years , 30 % women ) developed flutter . In multivariable analyses , smoking ( odds ratio [ OR ] 2.84 , 95 % confidence interval [ CI ] 1.54 - 5.23 ) , increased PR interval ( OR 1.28 per SD , 95 % CI 1.03 - 1.60 ) , myocardial infa rct ion ( OR 2.25 , 95 % CI 1.05 - 4.80 ) and heart failure ( OR 5.22 , 95 % CI 1.26 - 21.64 ) were associated with incident flutter . In age- and sex-adjusted models , flutter ( vs referents ) was associated with 10-year increased risk of AF ( hazard ratio [ HR ] 5.01 , 95 % CI 3.14 - 7.99 ) , myocardial infa rct ion ( HR 3.05 , 95 % CI 1.42 - 6.59 ) , heart failure ( HR 4.14 , 95 % CI 1.90 - 8.99 ) , stroke ( HR 2.17 , 95 % CI 1.13 - 4.17 ) , and mortality ( HR 2.00 , 95 % CI 1.44 - 2.79 ) . CONCLUSION We identified the clinical correlates associated with flutter and observed that flutter was associated with multiple adverse outcomes Background — Atrial fibrillation is associated with increased mortality , but the specific causes of death and their predictors have not been described among patients on effective anticoagulant therapy . Methods and Results — The R and omized Evaluation of Long-Term Anticoagulant Therapy ( RE-LY ) trial r and omized 18 113 patients ( age , 71.5±9 years ; male , 64 % ; CHADS2 score , 2.1±1 ) to receive dabigatran or warfarin .  Median follow-up was 2 years , and complete follow-up was achieved in 99.9 % of patients . All deaths were categorized by the investigators using prespecified definitions followed by central adjudication . Overall , 1371 deaths occurred ( annual mortality rate , 3.84 % ; 95 % confidence interval [ CI ] , 3.64–4.05 ) . Cardiac deaths ( sudden cardiac death and progressive heart failure ) accounted for 37.4 % of all deaths , whereas stroke- and hemorrhage-related deaths represented 9.8 % of the total mortality . An examination of the causes of death according to dabigatran or warfarin showed that dabigatran significantly reduced vascular ( embolism and hemorrhage-related ) mortality ( relative risk , 0.63 ; 95 % CI , 0.45–0.88 ; P=0.007 ) , whereas other causes of death were similar between treatments , including cardiac mortality ( relative risk , 0.96 ; 95 % CI , 0.80–1.15 ; P=0.638 ) . The two strongest independent predictors of cardiac death in this population were heart failure ( hazard ratio , 3.02 ; 95 % CI , 2.45–3.73 ; P<0.0001 ) , and prior myocardial infa rct ion ( hazard ratio , 2.05 ; 95 % CI , 1.61–2.62 ; P<0.0001 ) . Conclusions — The majority of deaths are not related to stroke in a contemporary anticoagulated atrial fibrillation population . These results emphasize the need to identify interventions beyond effective anticoagulation to further reduce mortality in atrial fibrillation . Clinical Trial Registration — URL : http://www . clinical trials.gov . Unique identifier : NCT00262600 Background — There is a modest risk of myocardial infa rct ion ( MI )  and myocardial ischemic events in patients with atrial fibrillation . Methods and Results — Data from the RE-LY study ( R and omized Evaluation of Long-Term Anticoagulation Therapy ) were used to report rates of MI , unstable angina , cardiac arrest , and cardiac death and the prespecified net clinical benefit and treatment effects of dabigatran versus warfarin .  MI occurred at annual rates of 0.82 % and 0.81 % with dabigatran 110 or 150 mg BID compared with 0.64 % with warfarin ( hazard ratio [ HR ] 1.29 , 95 % confidence interval [ CI ] 0.96–1.75 , P=0.09 for dabigatran 110 mg ; HR 1.27 , 95 % CI 0.94–1.71 , P=0.12 for dabigatran 150 mg ) . Annual rates of a composite of MI , unstable angina , cardiac arrest , and cardiac death were 3.16 % per year with dabigatran 110 mg , 3.33 % per year with dabigatran 150 mg , and 3.41 % per year with warfarin ( HR versus warfarin 0.93 , 95 % CI 0.80–1.06 , P=0.28 for dabigatran 110 mg and HR 0.98 , 95 % CI 0.85–1.12 , P=0.77 for dabigatran 150 mg ) . Events prespecified as “ net clinical benefit ” ( all strokes , systemic embolism , MI , pulmonary embolism , major bleeding , and all-cause death ) occurred at a rate of 7.34 % per year with dabigatran 110 mg , 7.11 % per year with dabigatran 150 mg , and 7.91 % per year with warfarin ( HR 0.92 , 95 % CI 0.84–1.01 , P=0.09 for dabigatran 110 mg and HR 0.90 , 95 % CI 0.82–0.99 , P=0.02 for dabigatran 150 mg ) . The relative effects of dabigatran versus warfarin on myocardial ischemic events were consistent in patients with or without a baseline history of MI or coronary artery disease . Conclusions — There was a nonsignificant increase in MI with dabigatran compared with warfarin , but other myocardial ischemic events were not increased . Treatment effects of dabigatran were consistent in patients at higher and lower risk of myocardial ischemic events . Clinical Trial Registration — URL : http://www . clinical trials.gov . Unique identifier : NCT 00262600 BACKGROUND AND PURPOSE Thoracic aortic plaque identified by transesophageal echocardiography heightens the risk of stroke associated with atrial fibrillation ( AF ) . We sought to identify the prevalence , predictors , and implication s of aortic plaque in patients with nonvalvular AF . METHODS Thoracic aortic plaque was prospect ively sought in 770 persons with AF with 
    Output:
    