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 — Recent studies have investigated alternatives to warfarin for stroke prophylaxis in patients with atrial fibrillation ( AF ) , but whether these alternatives are cost-effective is unknown . Methods and Results — On the basis of the results from R and omized Evaluation of Long Term Anticoagulation Therapy ( RE-LY ) and other trials , we developed a decision- analysis model to compare the cost and quality -adjusted survival of various antithrombotic therapies . We ran our Markov model in a hypothetical cohort of 70-year-old patients with AF using a cost-effectiveness threshold of $ 50 000/ quality -adjusted life-year . We estimated the cost of dabigatran as US $ 9 a day . For a patient with an average risk of major hemorrhage ( ≈3%/y ) , the most cost-effective therapy depended on stroke risk . For patients with the lowest stroke rate ( CHADS2 stroke score of 0 ) , only aspirin was cost-effective . For patients with a moderate stroke rate ( CHADS2 score of 1 or 2 ) , warfarin was cost-effective unless the risk of hemorrhage was high or quality of international normalized ratio control was poor ( time in the therapeutic range < 57.1 % ) . For patients with a high stroke risk ( CHADS2 stroke score ≥3 ) , dabigatran 150 mg ( twice daily ) was cost-effective unless international normalized ratio control was excellent ( time in the therapeutic range > 72.6 % ) . Neither dabigatran 110 mg nor dual therapy ( aspirin and clopidogrel ) was cost-effective . Conclusions — Dabigatran 150 mg ( twice daily ) was cost-effective in AF population s at high risk of hemorrhage or high risk of stroke unless international normalized ratio control with warfarin was excellent . Warfarin was cost-effective in moderate-risk AF population s unless international normalized ratio control was poor Objectives To determine the incremental net health benefits of dabigatran etexilate 110 mg and 150 mg twice daily and warfarin in patients with non-valvular atrial fibrillation and to estimate the cost effectiveness of dabigatran in the United Kingdom . Design Quantitative benefit-harm and economic analyses using a discrete event simulation model to extrapolate the findings of the RE-LY ( R and omized Evaluation of Long-Term Anticoagulation Therapy ) study to a lifetime horizon . Setting UK National Health Service . Population Cohorts of 50 000 simulated patients at moderate to high risk of stroke with a mean baseline CHADS2 ( Congestive heart failure , Hypertension , Age≥75 years , Diabetes mellitus , previous Stroke/transient ischaemic attack ) score of 2.1 . Main outcome measures Quality adjusted life years ( QALYs ) gained and incremental cost per QALY of dabigatran compared with warfarin . Results Compared with warfarin , low dose and high dose dabigatran were associated with positive incremental net benefits of 0.094 ( 95 % central range −0.083 to 0.267 ) and 0.146 ( −0.029 to 0.322 ) QALYs . Positive incremental net benefits result ed for high dose dabigatran in 94 % of simulations versus warfarin and in 76 % of those versus low dose dabigatran . In the economic analysis , high dose dabigatran dominated the low dose , had an incremental cost effectiveness ratio of £ 23 082 ( € 26 700 ; $ 35 800 ) per QALY gained versus warfarin , and was more cost effective in patients with a baseline CHADS2 score of 3 or above . However , at centres that achieved good control of international normalised ratio , such as those in the UK , dabigatran 150 mg was not cost effective , at £ 42 386 per QALY gained . Conclusions This analysis supports regulatory decisions that dabigatran offers a positive benefit to harm ratio when compared with warfarin . However , no subgroup for which dabigatran 110 mg offered any clinical or economic advantage over 150 mg was identified . High dose dabigatran will be cost effective only for patients at increased risk of stroke or for whom international normalised ratio is likely to be less well controlled 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 Oral dabigatran etexilate is indicated for the prevention of stroke and systemic embolism in patients with atrial fibrillation ( AF ) in whom anticoagulation is appropriate . Based on the RE-LY study we investigated the cost-effectiveness of Health Canada approved dabigatran etexilate dosing ( 150 mg bid for patients < 80 years , 110 mg bid for patients ≥80 years ) versus warfarin and " real-world " prescribing ( i.e. warfarin , aspirin , or no treatment in a cohort of warfarin-eligible patients ) from a Canadian payer perspective . A Markov model simulated AF patients at moderate to high risk of stroke while tracking clinical events [ primary and recurrent ischaemic strokes , systemic embolism , transient ischaemic attack , haemorrhage ( intracranial , extracranial , and minor ) , acute myocardial infa rct ion and death ] and result ing functional disability . Acute event costs and result ing long-term follow-up costs incurred by disabled stroke survivors were based on a Canadian prospect i ve study , published literature , and national statistics . Clinical events , summarized as events per 100 patient-years , quality -adjusted life years ( QALYs ) , total costs , and incremental cost effectiveness ratios ( ICER ) were calculated . Over a lifetime , dabigatran etexilate treated patients experienced fewer intracranial haemorrhages ( 0.49 dabigatran etexilate vs. 1.13 warfarin vs. 1.05 " real-world " prescribing ) and fewer ischaemic strokes ( 4.40 dabigatran etexilate vs. 4.66 warfarin vs. 5.16 " real-world " prescribing ) per 100 patient-years . The ICER  of dabigatran etexilate was $ 10,440/QALY versus warfarin and $ 3,962/QALY versus " real-world " prescribing . This study demonstrates that dabigatran etexilate is a highly cost-effective alternative to current care for the prevention of stroke and systemic embolism among Canadian AF patients Background and Purpose — Oral anticoagulants are effective at reducing stroke compared with aspirin in atrial fibrillation patients older than 75 years . Although the benefits of reduced stroke risk outweigh the risks of bleeding , the cost effectiveness of warfarin in this patient population has not yet been established . Methods — An economic evaluation was conducted alongside a r and omized , controlled trial ; 973 patients ≥75 years of age with atrial fibrillation were recruited from primary care and r and omly assigned to either take warfarin or aspirin . Follow-up was for a mean of 2.7 years . Costs of thrombotic and hemorrhagic events , anticoagulation clinic visits , and primary care utilization were determined . Clinical benefits were expressed in terms of a primary event avoided : fatal/nonfatal disabling stroke , intracranial hemorrhage , or systemic embolism . A cost-utility analysis was performed using quality -adjusted life years as the benefit measure . Results — Total costs over 4 years were lower in the warfarin group ( difference , −£165 ; 95 % CI , −£452–£89 ) , primarily driven by the difference in primary event costs . The primary event rate over 4 years was lower in the warfarin group ( 0.049 versus 0.099 ) , and the quality -adjusted life years score was higher ( difference , 0.02 ; 95 % CI , −0.07–0.11 ) . With lower costs and a higher quality -adjusted life years score , warfarin is the dominant treatment , but the differences in both costs and effects are small . Conclusions — Warfarin is cost-effective compared with aspirin in atrial fibrillation patients age ≥75 years . These data support the anticoagulant therapy option in this high-risk patient population . However , the small differences in costs and effects indicate the importance of exploring patient preferences 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 — Stroke risk increases with age in patients who have nonvalvular atrial fibrillation . It is uncertain whether the efficacy of stroke prevention therapies in atrial fibrillation changes as patients age . The objective of this study was to determine the effect of age on the relative efficacy of oral anticoagulants ( OAC ) and antiplatelet ( AP ) therapy ( including acetylsalicylic acid and triflusal ) on ischemic stroke , serious bleeding , and vascular events in patients with atrial fibrillation . Methods — This is an analysis of the Atrial Fibrillation Investigators data base , which contains patient level- data from r and omized trials of stroke prevention in atrial fibrillation . We used Cox regression models with age as a continuous variable that controlled for sex , year of r and omization , and history of cerebrovascular disease , diabetes , hypertension , and congestive heart failure . Outcomes included ischemic stroke , serious bleeding ( intracranial hemorrhage or systemic bleeding requiring hospitalization , transfusion , or surgery ) , and cardiovascular events ( ischemic stroke , myocardial infa rct ion , systemic embolism , or v 
    Output:
    
agent
The various risk stratification schemes classified variable proportions as low , moderate and high risk , but the CHA(2)DS(2)-VASc score classified the smallest proportion of patients as ' low risk ' .
Anticoagulation with vitamin K antagonists and dabigatran is cost-effective in patients at high risk of stroke , but not in patients without any other stroke risk factor beside AF .
***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 — Recent studies have investigated alternatives to warfarin for stroke prophylaxis in patients with atrial fibrillation ( AF ) , but whether these alternatives are cost-effective is unknown . Methods and Results — On the basis of the results from R and omized Evaluation of Long Term Anticoagulation Therapy ( RE-LY ) and other trials , we developed a decision- analysis model to compare the cost and quality -adjusted survival of various antithrombotic therapies . We ran our Markov model in a hypothetical cohort of 70-year-old patients with AF using a cost-effectiveness threshold of $ 50 000/ quality -adjusted life-year . We estimated the cost of dabigatran as US $ 9 a day . For a patient with an average risk of major hemorrhage ( ≈3%/y ) , the most cost-effective therapy depended on stroke risk . For patients with the lowest stroke rate ( CHADS2 stroke score of 0 ) , only aspirin was cost-effective . For patients with a moderate stroke rate ( CHADS2 score of 1 or 2 ) , warfarin was cost-effective unless the risk of hemorrhage was high or quality of international normalized ratio control was poor ( time in the therapeutic range < 57.1 % ) . For patients with a high stroke risk ( CHADS2 stroke score ≥3 ) , dabigatran 150 mg ( twice daily ) was cost-effective unless international normalized ratio control was excellent ( time in the therapeutic range > 72.6 % ) . Neither dabigatran 110 mg nor dual therapy ( aspirin and clopidogrel ) was cost-effective . Conclusions — Dabigatran 150 mg ( twice daily ) was cost-effective in AF population s at high risk of hemorrhage or high risk of stroke unless international normalized ratio control with warfarin was excellent . Warfarin was cost-effective in moderate-risk AF population s unless international normalized ratio control was poor Objectives To determine the incremental net health benefits of dabigatran etexilate 110 mg and 150 mg twice daily and warfarin in patients with non-valvular atrial fibrillation and to estimate the cost effectiveness of dabigatran in the United Kingdom . Design Quantitative benefit-harm and economic analyses using a discrete event simulation model to extrapolate the findings of the RE-LY ( R and omized Evaluation of Long-Term Anticoagulation Therapy ) study to a lifetime horizon . Setting UK National Health Service . Population Cohorts of 50 000 simulated patients at moderate to high risk of stroke with a mean baseline CHADS2 ( Congestive heart failure , Hypertension , Age≥75 years , Diabetes mellitus , previous Stroke/transient ischaemic attack ) score of 2.1 . Main outcome measures Quality adjusted life years ( QALYs ) gained and incremental cost per QALY of dabigatran compared with warfarin . Results Compared with warfarin , low dose and high dose dabigatran were associated with positive incremental net benefits of 0.094 ( 95 % central range −0.083 to 0.267 ) and 0.146 ( −0.029 to 0.322 ) QALYs . Positive incremental net benefits result ed for high dose dabigatran in 94 % of simulations versus warfarin and in 76 % of those versus low dose dabigatran . In the economic analysis , high dose dabigatran dominated the low dose , had an incremental cost effectiveness ratio of £ 23 082 ( € 26 700 ; $ 35 800 ) per QALY gained versus warfarin , and was more cost effective in patients with a baseline CHADS2 score of 3 or above . However , at centres that achieved good control of international normalised ratio , such as those in the UK , dabigatran 150 mg was not cost effective , at £ 42 386 per QALY gained . Conclusions This analysis supports regulatory decisions that dabigatran offers a positive benefit to harm ratio when compared with warfarin . However , no subgroup for which dabigatran 110 mg offered any clinical or economic advantage over 150 mg was identified . High dose dabigatran will be cost effective only for patients at increased risk of stroke or for whom international normalised ratio is likely to be less well controlled 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 Oral dabigatran etexilate is indicated for the prevention of stroke and systemic embolism in patients with atrial fibrillation ( AF ) in whom anticoagulation is appropriate . Based on the RE-LY study we investigated the cost-effectiveness of Health Canada approved dabigatran etexilate dosing ( 150 mg bid for patients < 80 years , 110 mg bid for patients ≥80 years ) versus warfarin and " real-world " prescribing ( i.e. warfarin , aspirin , or no treatment in a cohort of warfarin-eligible patients ) from a Canadian payer perspective . A Markov model simulated AF patients at moderate to high risk of stroke while tracking clinical events [ primary and recurrent ischaemic strokes , systemic embolism , transient ischaemic attack , haemorrhage ( intracranial , extracranial , and minor ) , acute myocardial infa rct ion and death ] and result ing functional disability . Acute event costs and result ing long-term follow-up costs incurred by disabled stroke survivors were based on a Canadian prospect i ve study , published literature , and national statistics . Clinical events , summarized as events per 100 patient-years , quality -adjusted life years ( QALYs ) , total costs , and incremental cost effectiveness ratios ( ICER ) were calculated . Over a lifetime , dabigatran etexilate treated patients experienced fewer intracranial haemorrhages ( 0.49 dabigatran etexilate vs. 1.13 warfarin vs. 1.05 " real-world " prescribing ) and fewer ischaemic strokes ( 4.40 dabigatran etexilate vs. 4.66 warfarin vs. 5.16 " real-world " prescribing ) per 100 patient-years . The ICER  of dabigatran etexilate was $ 10,440/QALY versus warfarin and $ 3,962/QALY versus " real-world " prescribing . This study demonstrates that dabigatran etexilate is a highly cost-effective alternative to current care for the prevention of stroke and systemic embolism among Canadian AF patients Background and Purpose — Oral anticoagulants are effective at reducing stroke compared with aspirin in atrial fibrillation patients older than 75 years . Although the benefits of reduced stroke risk outweigh the risks of bleeding , the cost effectiveness of warfarin in this patient population has not yet been established . Methods — An economic evaluation was conducted alongside a r and omized , controlled trial ; 973 patients ≥75 years of age with atrial fibrillation were recruited from primary care and r and omly assigned to either take warfarin or aspirin . Follow-up was for a mean of 2.7 years . Costs of thrombotic and hemorrhagic events , anticoagulation clinic visits , and primary care utilization were determined . Clinical benefits were expressed in terms of a primary event avoided : fatal/nonfatal disabling stroke , intracranial hemorrhage , or systemic embolism . A cost-utility analysis was performed using quality -adjusted life years as the benefit measure . Results — Total costs over 4 years were lower in the warfarin group ( difference , −£165 ; 95 % CI , −£452–£89 ) , primarily driven by the difference in primary event costs . The primary event rate over 4 years was lower in the warfarin group ( 0.049 versus 0.099 ) , and the quality -adjusted life years score was higher ( difference , 0.02 ; 95 % CI , −0.07–0.11 ) . With lower costs and a higher quality -adjusted life years score , warfarin is the dominant treatment , but the differences in both costs and effects are small . Conclusions — Warfarin is cost-effective compared with aspirin in atrial fibrillation patients age ≥75 years . These data support the anticoagulant therapy option in this high-risk patient population . However , the small differences in costs and effects indicate the importance of exploring patient preferences 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 — Stroke risk increases with age in patients who have nonvalvular atrial fibrillation . It is uncertain whether the efficacy of stroke prevention therapies in atrial fibrillation changes as patients age . The objective of this study was to determine the effect of age on the relative efficacy of oral anticoagulants ( OAC ) and antiplatelet ( AP ) therapy ( including acetylsalicylic acid and triflusal ) on ischemic stroke , serious bleeding , and vascular events in patients with atrial fibrillation . Methods — This is an analysis of the Atrial Fibrillation Investigators data base , which contains patient level- data from r and omized trials of stroke prevention in atrial fibrillation . We used Cox regression models with age as a continuous variable that controlled for sex , year of r and omization , and history of cerebrovascular disease , diabetes , hypertension , and congestive heart failure . Outcomes included ischemic stroke , serious bleeding ( intracranial hemorrhage or systemic bleeding requiring hospitalization , transfusion , or surgery ) , and cardiovascular events ( ischemic stroke , myocardial infa rct ion , systemic embolism , or v 
    Output:
    