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 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 Few data on the thromboembolic ( TE ) risk of paroxysmal and persistent atrial fibrillation ( AF ) are available . This study aim ed to assess the incidence of TE events in paroxysmal and persistent AF . Methods We performed a subset post hoc analysis of 771 patients with paroxysmal and 463 with persistent AF enrolled in the multicenter , prospect i ve , r and omized , double-blind , placebo-controlled GISSI-AF trial - comparing the efficacy of valsartan versus placebo in preventing AF recurrences – where the choice of antithrombotic treatment was left to the judgment of the referring physician . TE and major outcome events were central ly vali date d. AF recurrences were detected by frequent clinic visits and a transtelephonic monitoring device with weekly and symptomatic transmissions . Results Eighty-five percent of patients had a history of hypertension , and the 7.7 % had heart failure , left ventricular dysfunction , or both .  The mean CHADS2 score was 1.41±0.84 . TE and major bleeding events were observed at a low incidence among the overall population at 1-year follow-up ( 0.97 % and 0.81 % , respectively ) . The univariate and multivariable analyses revealed no statistically significant differences in the incidence of TE , major bleeding events or mortality in paroxysmal and persistent AF patients . TE events were more common among women than men ( p=0.02 ) . The follow-up examination showed under- or overtreatment with warfarin in many patients , according to guideline suggestions . Warfarin was more frequently prescribed to patients with persistent AF ( p<0.0001 ) and patients with AF recurrences ( p<0.0001 ) . AF recurrences were noninvasively detected in 632 ( 51.2 % ) patients . In patients without AF recurrences , the TE event rate was 0.5 % versus 1.74 % , 1.28 % , and 1.18 % for those with only symptomatic , only asymptomatic or both symptomatic and asymptomatic AF recurrences , respectively , but the difference was not statistically significant , even after adjusting for warfarin treatment and the CHADS2 score ( HR 2.93 ; CI 95 % ; 0.8 - 10.9 ; p=0.11 ) . Conclusions TE and major bleeding events showed a very low incidence in the GISSI-AF trial population , despite under- or overtreatment with warfarin in many patients . TE events had a similar rate in paroxysmal and persistent AF.Trial registration Trial registration number : AIMS To test the hypothesis that stroke and systemic embolic events ( SEE ) in the stroke prevention using an oral thrombin inhibitor in atrial fibrillation ( SPORTIF ) III and V trials are different between paroxysmal and persistent atrial fibrillation ( AF ) . METHODS Data analysis from two cohorts of patients enrolled in the prospect i ve SPORTIF III and V clinical trials ( n = 7329 ) ; 836 subjects ( 11.4 % ) with paroxysmal AF [ mean age 70.1 years ( SD = 9.5 ) ] were compared with 6493 subjects with persistent AF for this ancillary study . RESULTS The annual event rates for stroke/SEE are 1.73 % for persistent AF and 0.93 % for paroxysmal AF . In a multivariate analysis , after adjusting for stroke risk factors , gender and aspirin usage , the differences remained statistically significant with a higher hazard ratio ( HR ) for stroke/SEE in persistent AF [ vs. paroxysmal AF , HR 1.87 , 95 % confidence interval ( CI ) 1.04 - 3.36 ; P = 0.037 ] . In ' high risk ' patients ( with > or=2 stroke risk factors ) annual event rates for stroke/SEE were 2.08 % for persistent AF and 1.27 % for paroxysmal AF ( adjusted HR = 1.68 , 95 % CI 0.91 - 3.1 , P = 0.098 ) . Elderly patients had annual event rates for stroke/SEE of 2.38 % for persistent AF and 1.13 % for paroxysmal AF ( adjusted HR = 2.27 , 95 % CI 0.92 - 5.59 , P = 0.075 ) . Vitamin K antagonist (VKA)-naive paroxysmal AF patients had a 1.89%/year stroke/SEE rate , compared with 0.61 % for previous VKA takers ( HR = 0.33 , 95 % CI 0.11 - 1.01 , P = 0.052 ) . CONCLUSION In this large clinical trial cohort of anticoagulated AF patients , those with paroxysmal AF had stroke rates which were lower than for patients with persistent AF , although both groups had broadly similar stroke risk factors . Subjects with paroxysmal AF at ' high risk ' had stroke/SEE rates that were not significantly different to persistent AF subjects BACKGROUND Edoxaban is a direct oral factor Xa inhibitor with proven antithrombotic effects . The long-term efficacy and safety of edoxaban as compared with warfarin in patients with atrial fibrillation is not known . METHODS We conducted a r and omized , double-blind , double-dummy trial comparing two once-daily regimens of edoxaban with warfarin in 21,105 patients with moderate-to-high-risk atrial fibrillation ( median follow-up , 2.8 years ) . The primary efficacy end point was stroke or systemic embolism . Each edoxaban regimen was tested for noninferiority to warfarin during the treatment period . The principal safety end point was major bleeding . RESULTS The annualized rate of the primary end point during treatment was 1.50 % with warfarin ( median time in the therapeutic range , 68.4 % ) , as compared with 1.18 % with high-dose edoxaban ( hazard ratio , 0.79 ; 97.5 % confidence interval [ CI ] , 0.63 to 0.99 ; P<0.001 for noninferiority ) and 1.61 % with low-dose edoxaban ( hazard ratio , 1.07 ; 97.5 % CI , 0.87 to 1.31 ; P=0.005 for noninferiority ) . In the intention-to-treat analysis , there was a trend favoring high-dose edoxaban versus warfarin ( hazard ratio , 0.87 ; 97.5 % CI , 0.73 to 1.04 ; P=0.08 ) and an unfavorable trend with low-dose edoxaban versus warfarin ( hazard ratio , 1.13 ; 97.5 % CI , 0.96 to 1.34 ; P=0.10 ) . The annualized rate of major bleeding was 3.43 % with warfarin versus 2.75 % with high-dose edoxaban ( hazard ratio , 0.80 ; 95 % CI , 0.71 to 0.91 ; P<0.001 ) and 1.61 % with low-dose edoxaban ( hazard ratio , 0.47 ; 95 % CI , 0.41 to 0.55 ; P<0.001 ) . The corresponding annualized rates of death from cardiovascular causes were 3.17 % versus 2.74 % ( hazard ratio , 0.86 ; 95 % CI , 0.77 to 0.97 ; P=0.01 ) , and 2.71 % ( hazard ratio , 0.85 ; 95 % CI , 0.76 to 0.96 ; P=0.008 ) , and the corresponding rates of the key secondary end point ( a composite of stroke , systemic embolism , or death from cardiovascular causes ) were 4.43 % versus 3.85 % ( hazard ratio , 0.87 ; 95 % CI , 0.78 to 0.96 ; P=0.005 ) , and 4.23 % ( hazard ratio , 0.95 ; 95 % CI , 0.86 to 1.05 ; P=0.32 ) . CONCLUSIONS Both once-daily regimens of edoxaban were noninferior to warfarin with respect to the prevention of stroke or systemic embolism and were associated with significantly lower rates of bleeding and death from cardiovascular causes . ( Funded by Daiichi Sankyo Pharma Development ; ENGAGE AF-TIMI 48 Clinical Trials.gov number , NCT00781391 . ) INTRODUCTION Paroxysmal atrial fibrillation ( AF ) may progress to persistent AF . We studied the clinical correlates and the effect of rhythm-control strategy on AF progression . METHODS RecordAF was a worldwide prospect i ve survey of AF management . Consecutive eligible patients with recent-onset AF were included and allocated to rate or rhythm control according to patient/physician choice . A total of 2,137 patients were followed up for 12 months . Atrial fibrillation progression was defined as a change from paroxysmal to persistent/permanent AF . RESULTS Progression of AF occurred in 318 patients ( 15 % ) after 1 year . Patients with AF progression  were older ; had a higher diastolic blood 
    Output:
    
agent
Non-paroxysmal atrial fibrillation is associated with a highly significant increase in thromboembolism and death .
***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 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 Few data on the thromboembolic ( TE ) risk of paroxysmal and persistent atrial fibrillation ( AF ) are available . This study aim ed to assess the incidence of TE events in paroxysmal and persistent AF . Methods We performed a subset post hoc analysis of 771 patients with paroxysmal and 463 with persistent AF enrolled in the multicenter , prospect i ve , r and omized , double-blind , placebo-controlled GISSI-AF trial - comparing the efficacy of valsartan versus placebo in preventing AF recurrences – where the choice of antithrombotic treatment was left to the judgment of the referring physician . TE and major outcome events were central ly vali date d. AF recurrences were detected by frequent clinic visits and a transtelephonic monitoring device with weekly and symptomatic transmissions . Results Eighty-five percent of patients had a history of hypertension , and the 7.7 % had heart failure , left ventricular dysfunction , or both .  The mean CHADS2 score was 1.41±0.84 . TE and major bleeding events were observed at a low incidence among the overall population at 1-year follow-up ( 0.97 % and 0.81 % , respectively ) . The univariate and multivariable analyses revealed no statistically significant differences in the incidence of TE , major bleeding events or mortality in paroxysmal and persistent AF patients . TE events were more common among women than men ( p=0.02 ) . The follow-up examination showed under- or overtreatment with warfarin in many patients , according to guideline suggestions . Warfarin was more frequently prescribed to patients with persistent AF ( p<0.0001 ) and patients with AF recurrences ( p<0.0001 ) . AF recurrences were noninvasively detected in 632 ( 51.2 % ) patients . In patients without AF recurrences , the TE event rate was 0.5 % versus 1.74 % , 1.28 % , and 1.18 % for those with only symptomatic , only asymptomatic or both symptomatic and asymptomatic AF recurrences , respectively , but the difference was not statistically significant , even after adjusting for warfarin treatment and the CHADS2 score ( HR 2.93 ; CI 95 % ; 0.8 - 10.9 ; p=0.11 ) . Conclusions TE and major bleeding events showed a very low incidence in the GISSI-AF trial population , despite under- or overtreatment with warfarin in many patients . TE events had a similar rate in paroxysmal and persistent AF.Trial registration Trial registration number : AIMS To test the hypothesis that stroke and systemic embolic events ( SEE ) in the stroke prevention using an oral thrombin inhibitor in atrial fibrillation ( SPORTIF ) III and V trials are different between paroxysmal and persistent atrial fibrillation ( AF ) . METHODS Data analysis from two cohorts of patients enrolled in the prospect i ve SPORTIF III and V clinical trials ( n = 7329 ) ; 836 subjects ( 11.4 % ) with paroxysmal AF [ mean age 70.1 years ( SD = 9.5 ) ] were compared with 6493 subjects with persistent AF for this ancillary study . RESULTS The annual event rates for stroke/SEE are 1.73 % for persistent AF and 0.93 % for paroxysmal AF . In a multivariate analysis , after adjusting for stroke risk factors , gender and aspirin usage , the differences remained statistically significant with a higher hazard ratio ( HR ) for stroke/SEE in persistent AF [ vs. paroxysmal AF , HR 1.87 , 95 % confidence interval ( CI ) 1.04 - 3.36 ; P = 0.037 ] . In ' high risk ' patients ( with > or=2 stroke risk factors ) annual event rates for stroke/SEE were 2.08 % for persistent AF and 1.27 % for paroxysmal AF ( adjusted HR = 1.68 , 95 % CI 0.91 - 3.1 , P = 0.098 ) . Elderly patients had annual event rates for stroke/SEE of 2.38 % for persistent AF and 1.13 % for paroxysmal AF ( adjusted HR = 2.27 , 95 % CI 0.92 - 5.59 , P = 0.075 ) . Vitamin K antagonist (VKA)-naive paroxysmal AF patients had a 1.89%/year stroke/SEE rate , compared with 0.61 % for previous VKA takers ( HR = 0.33 , 95 % CI 0.11 - 1.01 , P = 0.052 ) . CONCLUSION In this large clinical trial cohort of anticoagulated AF patients , those with paroxysmal AF had stroke rates which were lower than for patients with persistent AF , although both groups had broadly similar stroke risk factors . Subjects with paroxysmal AF at ' high risk ' had stroke/SEE rates that were not significantly different to persistent AF subjects BACKGROUND Edoxaban is a direct oral factor Xa inhibitor with proven antithrombotic effects . The long-term efficacy and safety of edoxaban as compared with warfarin in patients with atrial fibrillation is not known . METHODS We conducted a r and omized , double-blind , double-dummy trial comparing two once-daily regimens of edoxaban with warfarin in 21,105 patients with moderate-to-high-risk atrial fibrillation ( median follow-up , 2.8 years ) . The primary efficacy end point was stroke or systemic embolism . Each edoxaban regimen was tested for noninferiority to warfarin during the treatment period . The principal safety end point was major bleeding . RESULTS The annualized rate of the primary end point during treatment was 1.50 % with warfarin ( median time in the therapeutic range , 68.4 % ) , as compared with 1.18 % with high-dose edoxaban ( hazard ratio , 0.79 ; 97.5 % confidence interval [ CI ] , 0.63 to 0.99 ; P<0.001 for noninferiority ) and 1.61 % with low-dose edoxaban ( hazard ratio , 1.07 ; 97.5 % CI , 0.87 to 1.31 ; P=0.005 for noninferiority ) . In the intention-to-treat analysis , there was a trend favoring high-dose edoxaban versus warfarin ( hazard ratio , 0.87 ; 97.5 % CI , 0.73 to 1.04 ; P=0.08 ) and an unfavorable trend with low-dose edoxaban versus warfarin ( hazard ratio , 1.13 ; 97.5 % CI , 0.96 to 1.34 ; P=0.10 ) . The annualized rate of major bleeding was 3.43 % with warfarin versus 2.75 % with high-dose edoxaban ( hazard ratio , 0.80 ; 95 % CI , 0.71 to 0.91 ; P<0.001 ) and 1.61 % with low-dose edoxaban ( hazard ratio , 0.47 ; 95 % CI , 0.41 to 0.55 ; P<0.001 ) . The corresponding annualized rates of death from cardiovascular causes were 3.17 % versus 2.74 % ( hazard ratio , 0.86 ; 95 % CI , 0.77 to 0.97 ; P=0.01 ) , and 2.71 % ( hazard ratio , 0.85 ; 95 % CI , 0.76 to 0.96 ; P=0.008 ) , and the corresponding rates of the key secondary end point ( a composite of stroke , systemic embolism , or death from cardiovascular causes ) were 4.43 % versus 3.85 % ( hazard ratio , 0.87 ; 95 % CI , 0.78 to 0.96 ; P=0.005 ) , and 4.23 % ( hazard ratio , 0.95 ; 95 % CI , 0.86 to 1.05 ; P=0.32 ) . CONCLUSIONS Both once-daily regimens of edoxaban were noninferior to warfarin with respect to the prevention of stroke or systemic embolism and were associated with significantly lower rates of bleeding and death from cardiovascular causes . ( Funded by Daiichi Sankyo Pharma Development ; ENGAGE AF-TIMI 48 Clinical Trials.gov number , NCT00781391 . ) INTRODUCTION Paroxysmal atrial fibrillation ( AF ) may progress to persistent AF . We studied the clinical correlates and the effect of rhythm-control strategy on AF progression . METHODS RecordAF was a worldwide prospect i ve survey of AF management . Consecutive eligible patients with recent-onset AF were included and allocated to rate or rhythm control according to patient/physician choice . A total of 2,137 patients were followed up for 12 months . Atrial fibrillation progression was defined as a change from paroxysmal to persistent/permanent AF . RESULTS Progression of AF occurred in 318 patients ( 15 % ) after 1 year . Patients with AF progression  were older ; had a higher diastolic blood 
    Output:
    