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: Importance The Apixaban for Reduction in Stroke and Other Thromboembolic Events in Atrial Fibrillation ( ARISTOTLE ) trial reported that apixaban therapy was superior to warfarin therapy in preventing stroke and all-cause death while causing significantly fewer major bleeds . To establish the value proposition of substituting apixiban therapy for warfarin therapy in patients with atrial fibrillation , we performed a cost-effectiveness analysis using patient-level data from the ARISTOTLE trial . Objective To assess the cost and cost-effectiveness of apixaban therapy compared with warfarin therapy in patients with atrial fibrillation from the perspective of the US health care system . Design , Setting , and Participants This economic analysis uses patient-level re source use and clinical data collected in the ARISTOTLE trial , a multinational r and omized clinical trial that observed 18 201 patients ( 3417 US patients ) for a median of 1.8 years between 2006 and 2011 . Interventions Apixaban therapy vs warfarin therapy . Main Outcomes and Measures Within-trial re source use and cost were compared between treatments , using externally derived US cost weights . Life expectancies for US patients were estimated according to their baseline risk and treatment using time-based and age-based survival models developed using the overall ARISTOTLE population . Quality -of-life adjustment factors were obtained from external sources . Cost-effectiveness ( incremental cost per quality -adjusted life-year gained ) was evaluated from a US perspective , and extensive sensitivity analyses were performed . Results Of the 3417 US patients enrolled in ARISTOTLE , the mean ( SD ) age was 71 ( 10 ) years ; 2329 ( 68.2 % ) were male and 3264 ( 95.5 % ) were white . After 2 years of anticoagulation therapy , health care costs ( excluding the study drug ) of patients treated with apixaban therapy and warfarin therapy were not statistically different ( difference , −$60 ; 95 % CI , −$2728 to $ 2608 ) . Life expectancy , modeled from ARISTOTLE outcomes , was significantly longer with apixaban therapy vs warfarin therapy ( 7.94 vs 7.54 quality -adjusted life years ) . The incremental cost , including cost of anticoagulant and monitoring , of achieving these benefits was within accepted US norms ( $ 53 925 per quality -adjusted life year , with 98 % likelihood of meeting a $ 100 000 willingness-to-pay threshold ) . Results were generally consistent when model assumptions were varied , with lifetime cost-effectiveness most affected by the price of apixaban and the time horizon . Conclusions and Relevance Apixaban therapy for ARISTOTLE-eligible patients with atrial fibrillation provides clinical benefits at an incremental cost that represents reasonable value for money judged using US benchmarks for cost-effectiveness . Trial Registration clinical trials.gov Identifier : Abstract Aim We tested the hypothesis that left ventricular hypertrophy ( LVH ) interferes with the antithrombotic effects of dabigatran and warfarin in patients with atrial fibrillation ( AF ) . Methods and results This is a post-hoc analysis of the R and omized Evaluation of Long-term anticoagulation therapY ( RE-LY ) Study . We defined LVH by electrocardiography ( ECG ) and included patients with AF on the ECG tracing at entry .  Hazard ratios ( HR ) for each dabigatran dose vs. warfarin were calculated in relation to LVH . LVH was present in 2353 ( 22.7 % ) out of 10 372 patients . In patients without LVH , the rates of primary outcome were 1.59%/year with warfarin , 1.60 % with dabigatran 110 mg ( HR vs. warfarin 1.01 , 95 % confidence interval ( CI ) 0.75–1.36 ) and 1.08 % with dabigatran 150 mg ( HR vs. warfarin 0.68 , 95 % CI 0.49–0.95 ) . In patients with LVH , the rates of primary outcome were 3.21%/year with warfarin , 1.69 % with dabigatran 110 mg ( HR vs. warfarin 0.52 , 95 % CI 0.32–0.84 ) and 1.55 % with 150 mg ( HR vs. warfarin 0.48 , 95 % CI 0.29–0.78 ) . The interaction between LVH status and dabigatran 110 mg vs. warfarin was significant for the primary outcome ( P = 0.021 ) and stroke ( P = 0.016 ) . LVH was associated with a higher event rate with warfarin , not with dabigatran . In the warfarin group , the time in therapeutic range was significantly lower in the presence than in the absence of LVH . Conclusions LVH was associated with a lower antithrombotic efficacy of warfarin , but not of dabigatran , in patients with AF . Consequently , the relative benefit of the lower dose of dabigatran compared to warfarin was enhanced in patients with LVH . The higher dose of dabigatran was superior to warfarin regardless of LVH status . Clinical trial registration http : www . clinical trials.gov . Unique identifier : NCT00262600 BACKGROUND Comorbid chronic obstructive pulmonary disease ( COPD ) is associated with poor outcomes among patients with cardiovascular disease . The risks of stroke and mortality associated with COPD among patients with atrial fibrillation are not well understood . METHODS We analyzed patients from ARISTOTLE , a r and omized trial of 18,201 patients with atrial fibrillation comparing the effects of apixaban versus warfarin on the risk of stroke or systemic embolism . Using Cox proportional hazards models , we assessed the associations between comorbid COPD and risk of stroke or systemic embolism and of mortality , adjusting for treatment allocation , smoking history and other risk factors . RESULTS COPD was present in 1950 ( 10.8 % ) of 18,134 patients with data on pulmonary disease history . After multivariable adjustment , COPD was not associated with risk of stroke or systemic embolism ( adjusted HR 0.85 [ 95 % CI 0.60 , 1.21 ] , p=0.356 ) . However , COPD was associated with a higher risk of all-cause mortality ( adjusted HR 1.60 [ 95 % CI 1.36 , 1.88 ] , p<0.001 ) and both cardiovascular and non-cardiovascular mortality . The benefit of apixaban over warfarin on stroke or systemic embolism was consistent among patients with and without COPD ( HR 0.92 [ 95 % CI 0.52 , 1.63 ] versus 0.78 [ 95 % CI 0.65 , 0.95 ] , interaction p=0.617 ) . CONCLUSIONS COPD was independently associated with increased risk of cardiovascular and non-cardiovascular mortality among patients with atrial fibrillation , but was not associated with risk of stroke or systemic embolism . The effect of apixaban on stroke or systemic embolism in COPD patients was consistent with its effect in the overall trial population BACKGROUND Warfarin reduces the risk of stroke in patients with atrial fibrillation but increases the risk of hemorrhage and is difficult to use . Dabigatran is a new oral direct thrombin inhibitor . METHODS In this noninferiority trial , we r and omly assigned 18,113 patients who had atrial fibrillation and a risk of stroke to receive , in a blinded fashion , fixed doses of dabigatran--110 mg or 150 mg twice daily -- or , in an unblinded fashion , adjusted-dose warfarin . The median duration of the follow-up period was 2.0 years . The primary outcome was stroke or systemic embolism . RESULTS Rates of the primary outcome were 1.69 % per year in the warfarin group , as compared with 1.53 % per year in the group that received 110 mg of dabigatran ( relative risk with dabigatran , 0.91 ; 95 % confidence interval [ CI ] , 0.74 to 1.11 ; P<0.001 for noninferiority ) and 1.11 % per year in the group that received 150 mg of dabigatran ( relative risk , 0.66 ; 95 % CI , 0.53 to 0.82 ; P<0.001 for superiority ) . The rate of major bleeding was 3.36 % per year in the warfarin group , as compared with 2.71 % per year in the group receiving 110 mg of dabigatran ( P=0.003 ) and 3.11 % per year in the group receiving 150 mg of dabigatran ( P=0.31 ) . The rate of hemorrhagic stroke was 0.38 % per year in the warfarin group , as compared with 0.12 % per year with 110 mg of dabigatran ( P<0.001 ) and 0.10 % per year with 150 mg of dabigatran ( P<0.001 ) . The mortality rate was 4.13 % per year in the warfarin group , as compared with 3.75 % per year with 110 mg of dabigatran ( P=0.13 ) and 3.64 % per year with 150 mg of dabigatran ( P=0.051 ) . CONCLUSIONS In patients with atrial fibrillation , dabigatran given at a dose of 110 mg was associated with rates of stroke and systemic embolism that were similar to those associated with warfarin , as well as lower rates of major hemorrhage .  Dabigatran administered at a dose of 150 mg , as compared with warfarin , was associated with lower rates of stroke and systemic embolism but similar rates of major hemorrhage . ( Clinical Trials.gov number , NCT00262600 . Aims The risk of stroke in patients with atrial fibrillation ( AF ) increases with age . In the ARISTOTLE trial , apixaban when compared with warfarin reduced the rate of stroke , death , and bleeding . We evaluated these outcomes in relation to patient age . Methods and results A total of 18 201 patients with AF and a raised risk of stroke were r and omized  to warfarin or apixaban 5 mg b.d . with dose reduction to 2.5 mg b.d . or placebo in 831 patients with ≥2 of the following criteria : age ≥80 years , body weight ≤60 kg , or creatinine ≥133 μmol/L. We used Cox models to compare outcomes in relation to patient age during 1.8 years median follow-up . Of the trial population , 30 % were < 65 years , 39 % were 65 to < 75 , and 31 % were ≥75 years . The rates of stroke , all-cause death , and major bleeding were higher in the older age groups ( P < 0.001 for all ) . Apixaban was more effective than warfarin  in preventing stroke and reducing mortality across all age groups , and associated with less major bleeding , less total bleeding , and less intracranial haemorrhage regardless of age ( P interaction > 0.11 for all ) . Results were also consistent for the 13 % of patients ≥80 years . No significant interaction with apixaban dose was found with respect to treatment effect on major outcomes . Conclusion The benefits of apixaban vs. warfarin were consistent in patients with AF regardless of age . Owing to the higher risk at older age , the absolute benefits of apixaban were greater in the elderly Background Patients with atrial fibrillation ( AF ) are prone to cardiovascular events and anticoagulation‐related bleeding complications . We hypothesized that patients with anemia are at increased risk for these outcomes . Methods We performed a post hoc analysis of the ARISTOTLE trial , which included > 18,000 patients with AF r and omized to warfarin ( target international normalized ratio , 2.0‐3.0 ) or apixaban 5 mg twice daily .  Multivariable Cox regression analysis was used to determine if anemia ( defined as hemoglobin < 13.0 in men and < 12.0 g/dL in women ) was associated with future stroke , major bleeding , or mortality . Results Anemia was present at baseline in 12.6 % of the ARISTOTLE population . Patients with anemia were older , had higher mean CHADS2 and HAS‐BLED scores , and were more likely to have experienced previous bleeding events . Anemia was associated with major bleeding ( adjusted hazard ratio [ HR ] , 1.92 ; 95 % CI , 1.62‐2.28 ; P < .0001 ) and all‐cause mortality ( adjusted HR , 1.68 ; 95 % CI , 1.46‐1.93 ; P < .0001 ) but not stroke or systemic embolism ( adjusted HR , 0.92 ; 95 % CI , 0.70‐1.21 ) . The benefits of apixaban compared with warfarin  on the rates of stroke , mortality , and bleeding events were 
    Output:
    
agent
Warfarin Versus Thrombin Inhibitor ( Dabigatran ) The RE-LY trial ( 9 , 18 ) showed that treatment with dabigatran , 150 mg , is superior to warfarin in reducing the incidence of the composite outcome of stroke or systemic embolism .
No statistically significant difference was observed between the 2 therapies with regard to major bleeding , myocardial infa rct ion , or
***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: Importance The Apixaban for Reduction in Stroke and Other Thromboembolic Events in Atrial Fibrillation ( ARISTOTLE ) trial reported that apixaban therapy was superior to warfarin therapy in preventing stroke and all-cause death while causing significantly fewer major bleeds . To establish the value proposition of substituting apixiban therapy for warfarin therapy in patients with atrial fibrillation , we performed a cost-effectiveness analysis using patient-level data from the ARISTOTLE trial . Objective To assess the cost and cost-effectiveness of apixaban therapy compared with warfarin therapy in patients with atrial fibrillation from the perspective of the US health care system . Design , Setting , and Participants This economic analysis uses patient-level re source use and clinical data collected in the ARISTOTLE trial , a multinational r and omized clinical trial that observed 18 201 patients ( 3417 US patients ) for a median of 1.8 years between 2006 and 2011 . Interventions Apixaban therapy vs warfarin therapy . Main Outcomes and Measures Within-trial re source use and cost were compared between treatments , using externally derived US cost weights . Life expectancies for US patients were estimated according to their baseline risk and treatment using time-based and age-based survival models developed using the overall ARISTOTLE population . Quality -of-life adjustment factors were obtained from external sources . Cost-effectiveness ( incremental cost per quality -adjusted life-year gained ) was evaluated from a US perspective , and extensive sensitivity analyses were performed . Results Of the 3417 US patients enrolled in ARISTOTLE , the mean ( SD ) age was 71 ( 10 ) years ; 2329 ( 68.2 % ) were male and 3264 ( 95.5 % ) were white . After 2 years of anticoagulation therapy , health care costs ( excluding the study drug ) of patients treated with apixaban therapy and warfarin therapy were not statistically different ( difference , −$60 ; 95 % CI , −$2728 to $ 2608 ) . Life expectancy , modeled from ARISTOTLE outcomes , was significantly longer with apixaban therapy vs warfarin therapy ( 7.94 vs 7.54 quality -adjusted life years ) . The incremental cost , including cost of anticoagulant and monitoring , of achieving these benefits was within accepted US norms ( $ 53 925 per quality -adjusted life year , with 98 % likelihood of meeting a $ 100 000 willingness-to-pay threshold ) . Results were generally consistent when model assumptions were varied , with lifetime cost-effectiveness most affected by the price of apixaban and the time horizon . Conclusions and Relevance Apixaban therapy for ARISTOTLE-eligible patients with atrial fibrillation provides clinical benefits at an incremental cost that represents reasonable value for money judged using US benchmarks for cost-effectiveness . Trial Registration clinical trials.gov Identifier : Abstract Aim We tested the hypothesis that left ventricular hypertrophy ( LVH ) interferes with the antithrombotic effects of dabigatran and warfarin in patients with atrial fibrillation ( AF ) . Methods and results This is a post-hoc analysis of the R and omized Evaluation of Long-term anticoagulation therapY ( RE-LY ) Study . We defined LVH by electrocardiography ( ECG ) and included patients with AF on the ECG tracing at entry .  Hazard ratios ( HR ) for each dabigatran dose vs. warfarin were calculated in relation to LVH . LVH was present in 2353 ( 22.7 % ) out of 10 372 patients . In patients without LVH , the rates of primary outcome were 1.59%/year with warfarin , 1.60 % with dabigatran 110 mg ( HR vs. warfarin 1.01 , 95 % confidence interval ( CI ) 0.75–1.36 ) and 1.08 % with dabigatran 150 mg ( HR vs. warfarin 0.68 , 95 % CI 0.49–0.95 ) . In patients with LVH , the rates of primary outcome were 3.21%/year with warfarin , 1.69 % with dabigatran 110 mg ( HR vs. warfarin 0.52 , 95 % CI 0.32–0.84 ) and 1.55 % with 150 mg ( HR vs. warfarin 0.48 , 95 % CI 0.29–0.78 ) . The interaction between LVH status and dabigatran 110 mg vs. warfarin was significant for the primary outcome ( P = 0.021 ) and stroke ( P = 0.016 ) . LVH was associated with a higher event rate with warfarin , not with dabigatran . In the warfarin group , the time in therapeutic range was significantly lower in the presence than in the absence of LVH . Conclusions LVH was associated with a lower antithrombotic efficacy of warfarin , but not of dabigatran , in patients with AF . Consequently , the relative benefit of the lower dose of dabigatran compared to warfarin was enhanced in patients with LVH . The higher dose of dabigatran was superior to warfarin regardless of LVH status . Clinical trial registration http : www . clinical trials.gov . Unique identifier : NCT00262600 BACKGROUND Comorbid chronic obstructive pulmonary disease ( COPD ) is associated with poor outcomes among patients with cardiovascular disease . The risks of stroke and mortality associated with COPD among patients with atrial fibrillation are not well understood . METHODS We analyzed patients from ARISTOTLE , a r and omized trial of 18,201 patients with atrial fibrillation comparing the effects of apixaban versus warfarin on the risk of stroke or systemic embolism . Using Cox proportional hazards models , we assessed the associations between comorbid COPD and risk of stroke or systemic embolism and of mortality , adjusting for treatment allocation , smoking history and other risk factors . RESULTS COPD was present in 1950 ( 10.8 % ) of 18,134 patients with data on pulmonary disease history . After multivariable adjustment , COPD was not associated with risk of stroke or systemic embolism ( adjusted HR 0.85 [ 95 % CI 0.60 , 1.21 ] , p=0.356 ) . However , COPD was associated with a higher risk of all-cause mortality ( adjusted HR 1.60 [ 95 % CI 1.36 , 1.88 ] , p<0.001 ) and both cardiovascular and non-cardiovascular mortality . The benefit of apixaban over warfarin on stroke or systemic embolism was consistent among patients with and without COPD ( HR 0.92 [ 95 % CI 0.52 , 1.63 ] versus 0.78 [ 95 % CI 0.65 , 0.95 ] , interaction p=0.617 ) . CONCLUSIONS COPD was independently associated with increased risk of cardiovascular and non-cardiovascular mortality among patients with atrial fibrillation , but was not associated with risk of stroke or systemic embolism . The effect of apixaban on stroke or systemic embolism in COPD patients was consistent with its effect in the overall trial population BACKGROUND Warfarin reduces the risk of stroke in patients with atrial fibrillation but increases the risk of hemorrhage and is difficult to use . Dabigatran is a new oral direct thrombin inhibitor . METHODS In this noninferiority trial , we r and omly assigned 18,113 patients who had atrial fibrillation and a risk of stroke to receive , in a blinded fashion , fixed doses of dabigatran--110 mg or 150 mg twice daily -- or , in an unblinded fashion , adjusted-dose warfarin . The median duration of the follow-up period was 2.0 years . The primary outcome was stroke or systemic embolism . RESULTS Rates of the primary outcome were 1.69 % per year in the warfarin group , as compared with 1.53 % per year in the group that received 110 mg of dabigatran ( relative risk with dabigatran , 0.91 ; 95 % confidence interval [ CI ] , 0.74 to 1.11 ; P<0.001 for noninferiority ) and 1.11 % per year in the group that received 150 mg of dabigatran ( relative risk , 0.66 ; 95 % CI , 0.53 to 0.82 ; P<0.001 for superiority ) . The rate of major bleeding was 3.36 % per year in the warfarin group , as compared with 2.71 % per year in the group receiving 110 mg of dabigatran ( P=0.003 ) and 3.11 % per year in the group receiving 150 mg of dabigatran ( P=0.31 ) . The rate of hemorrhagic stroke was 0.38 % per year in the warfarin group , as compared with 0.12 % per year with 110 mg of dabigatran ( P<0.001 ) and 0.10 % per year with 150 mg of dabigatran ( P<0.001 ) . The mortality rate was 4.13 % per year in the warfarin group , as compared with 3.75 % per year with 110 mg of dabigatran ( P=0.13 ) and 3.64 % per year with 150 mg of dabigatran ( P=0.051 ) . CONCLUSIONS In patients with atrial fibrillation , dabigatran given at a dose of 110 mg was associated with rates of stroke and systemic embolism that were similar to those associated with warfarin , as well as lower rates of major hemorrhage .  Dabigatran administered at a dose of 150 mg , as compared with warfarin , was associated with lower rates of stroke and systemic embolism but similar rates of major hemorrhage . ( Clinical Trials.gov number , NCT00262600 . Aims The risk of stroke in patients with atrial fibrillation ( AF ) increases with age . In the ARISTOTLE trial , apixaban when compared with warfarin reduced the rate of stroke , death , and bleeding . We evaluated these outcomes in relation to patient age . Methods and results A total of 18 201 patients with AF and a raised risk of stroke were r and omized  to warfarin or apixaban 5 mg b.d . with dose reduction to 2.5 mg b.d . or placebo in 831 patients with ≥2 of the following criteria : age ≥80 years , body weight ≤60 kg , or creatinine ≥133 μmol/L. We used Cox models to compare outcomes in relation to patient age during 1.8 years median follow-up . Of the trial population , 30 % were < 65 years , 39 % were 65 to < 75 , and 31 % were ≥75 years . The rates of stroke , all-cause death , and major bleeding were higher in the older age groups ( P < 0.001 for all ) . Apixaban was more effective than warfarin  in preventing stroke and reducing mortality across all age groups , and associated with less major bleeding , less total bleeding , and less intracranial haemorrhage regardless of age ( P interaction > 0.11 for all ) . Results were also consistent for the 13 % of patients ≥80 years . No significant interaction with apixaban dose was found with respect to treatment effect on major outcomes . Conclusion The benefits of apixaban vs. warfarin were consistent in patients with AF regardless of age . Owing to the higher risk at older age , the absolute benefits of apixaban were greater in the elderly Background Patients with atrial fibrillation ( AF ) are prone to cardiovascular events and anticoagulation‐related bleeding complications . We hypothesized that patients with anemia are at increased risk for these outcomes . Methods We performed a post hoc analysis of the ARISTOTLE trial , which included > 18,000 patients with AF r and omized to warfarin ( target international normalized ratio , 2.0‐3.0 ) or apixaban 5 mg twice daily .  Multivariable Cox regression analysis was used to determine if anemia ( defined as hemoglobin < 13.0 in men and < 12.0 g/dL in women ) was associated with future stroke , major bleeding , or mortality . Results Anemia was present at baseline in 12.6 % of the ARISTOTLE population . Patients with anemia were older , had higher mean CHADS2 and HAS‐BLED scores , and were more likely to have experienced previous bleeding events . Anemia was associated with major bleeding ( adjusted hazard ratio [ HR ] , 1.92 ; 95 % CI , 1.62‐2.28 ; P < .0001 ) and all‐cause mortality ( adjusted HR , 1.68 ; 95 % CI , 1.46‐1.93 ; P < .0001 ) but not stroke or systemic embolism ( adjusted HR , 0.92 ; 95 % CI , 0.70‐1.21 ) . The benefits of apixaban compared with warfarin  on the rates of stroke , mortality , and bleeding events were 
    Output:
    