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 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 . 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 . ) Background —Physical activity ( PA ) has previously been suggested to attenuate the risk of atrial fibrillation ( AF ) conferred by excess body weight and weight gain . We prospect ively examined the relationship between body size , weight change , and level of PA in a biracial cohort of middle-aged men and women . Methods and Results —Baseline characteristics on risk factor levels were obtained on 14 219 participants from the Atherosclerosis Risk in Communities Study . AF incidence was ascertained from 1987 to 2009 . Adjusted Cox proportional hazards models were used to estimate the associations between body mass index , waist circumference , relative weight change , and PA level with incident AF . During follow-up , there were 1775 cases of incident AF . Body mass index and waist circumference were positively associated with AF as was weight loss/gain of > 5 % initial body weight . An ideal level of PA had a small protective effect on AF risk and partially attenuated the risk of AF associated with excess weight in men but not women : compared with men with a normal body mass index , the risk of AF in obese men with an ideal , intermediate , and poor level of PA at baseline was increased by 37 % , 129 % , and 156 % ( Pinteraction=0.04 ) . During follow-up , PA did not modify the association between weight gain and risk of AF . Conclusions —Obesity and extreme weight change are risk factors for incident AF , whereas being physically active is associated with a small reduction in risk . In men only , being physically active offset some , but not all , of the risk incurred with excess body weight BACKGROUND Obese patients have favorable outcomes in congestive heart failure , hypertension , peripheral vascular disease , and coronary artery disease . Obesity also has been linked with increased incidence of atrial fibrillation , but its influence on outcomes in atrial fibrillation patients has not been investigated . The objective of this research is to investigate the effect of obesity on outcomes in atrial fibrillation . METHODS The Atrial Fibrillation Follow-up Investigation of Rhythm Management ( AFFIRM ) study was one of the largest multicenter trials of atrial fibrillation , with 4060 patients . Subjects were r and omized to rate versus rhythm-control strategy . We performed a post hoc analysis of the National Heart , Lung and Blood Institute limited access data set of atrial fibrillation patients who had body mass index ( BMI ) data available in the AFFIRM study . BMI data were not available on 1542 patients . Patients with BMI > or=18.5 were split into normal ( 18.5 - 25 ) , overweight ( 25 - 30 ) , and obese ( > 30 ) categories as per BMI ( kg/m(2 ) ) . Multivariate Cox proportional hazards regression was used on the eligible 2492 patients . End points were all-cause mortality and cardiovascular mortality . RESULTS Over three fourths of all patients in our cohort were overweight or obese . There were 304 deaths ( 103 among normal weight , 108 among overweight , and 93 among obese ) and 148 cardiovascular deaths ( 54 among normal weight , 41 among overweight , and 53 among obese ) over a mean period of 3 years of patient follow-up . On multivariate analysis , overweight ( hazard ratio [ HR ] 0.64 ; 95 % confidence interval [ CI ] , 0.48 - 0.84 ; P=.001 ) and obese ( HR 0.80 ; 95 % CI , 0.68 - 0.93 ; P=.005 ) categories were associated with lower all-cause mortality as compared with normal weight . Overweight ( HR 0.40 ; 95 % CI , 0.26 - 0.60 ; P < .001 ) and obese patients ( HR 0.77 ; 95 % CI , 0.62 - 0.95 ; P=.01 ) also had lower cardiovascular mortality as compared with the normal weight patients . CONCLUSIONS Although in prior studies , obesity has been associated with increased risk of atrial fibrillation , an obesity paradox exists for outcomes in atrial fibrillation . Obese patients with atrial fibrillation appear to have better long-term outcomes than nonobese patients BACKGROUND Japanese patients with atrial fibrillation ( AF ) are generally small and lean , but knowledge of the clinical characteristics of those with low body weight ( LBW : ≤50 kg ) is limited . METHODS AND RESULTS The Fushimi AF Registry is a community-based prospect i ve survey of AF patients who visited the participating medical institutions in Fushmi-ku , Japan . The BW and follow-up data were available for 2,945 patients . We compared the background and the incidence of clinical events during a median follow-up of 746 days between a LBW and non-LBW group . Patients in the LBW group accounted for 26.8 % ( 788 patients ) of the total . The LBW group was more often female , older , and had higher CHADS2score . The incidence of stroke/systemic embolism ( SE ) during follow-up was higher in the LBW group ( hazard ratio ( HR ) : 2.19 , 95 % confidence interval ( CI ) : 1.57 - 3.04 ; P<0.01 ) , whereas that of major bleeding was comparable ( HR : 1.05 , 95 % CI : 0.64 - 1.68 ; P=0.84 ) . This trend was consistently observed in the subgroups stratified by age , sex , and oral anticoagulant prescription at baseline . Multivariate analysis as well as propensity-score matching analysis further supported the significance of LBW as a risk of stroke/SE . CONCLUSIONS Patients in the LBW group had high risk profiles and showed a higher incidence of stroke/SE , but the incidence of major bleeding was not particularly high BACKGROUND The use of warfarin reduces the rate of ischemic stroke in patients with atrial fibrillation but requires frequent monitoring and dose adjustment . Rivaroxaban , an oral factor Xa inhibitor , may provide more consistent and predictable anticoagulation than warfarin . METHODS In a double-blind trial , we r and omly assigned 14,264 patients with nonvalvular atrial fibrillation who were at increased risk for stroke to receive either rivaroxaban ( at a daily dose of 20 mg ) or dose-adjusted warfarin . The per- protocol , as-treated primary analysis was design ed to determine whether rivaroxaban was noninferior to warfarin for the primary end point of stroke or systemic embolism . RESULTS In the primary analysis , the primary end point occurred in 188 patients in the rivaroxaban group ( 1.7 % per year ) and in 241 in the warfarin group ( 2.2 % per year ) ( hazard ratio in the rivaroxaban group , 0.79 ; 95 % confidence interval [ CI ] , 0.6 
    Output:
    
agent
Results — An obesity paradox was found for cardiovascular death and all-cause death in the subgroup analyses of r and omized trial cohorts ; however , observational studies fail to show this relationship .
Conclusions — There may be an obesity paradox in atrial fibrillation patients , particularly for all-cause and cardiovascular death outcomes .
An obesity paradox was also evident for stroke/systemic embolic event outcome in NOAC trials , with a treatment effect favoring NOACs over warfarin for both efficacy and safety that was significant only for normal weight patients
***TASK*** the task is to summarize an input biomedical literature in six sentences 
    ***INPUT*** the input is a biomedical literature 
    ***OUTPUT*** the output is the summary of an input biomedical literature in six sentences 
    ***DOCUMENTATION*** 
    ***EXAMPLES*** 
    Input: 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 . 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 . ) Background —Physical activity ( PA ) has previously been suggested to attenuate the risk of atrial fibrillation ( AF ) conferred by excess body weight and weight gain . We prospect ively examined the relationship between body size , weight change , and level of PA in a biracial cohort of middle-aged men and women . Methods and Results —Baseline characteristics on risk factor levels were obtained on 14 219 participants from the Atherosclerosis Risk in Communities Study . AF incidence was ascertained from 1987 to 2009 . Adjusted Cox proportional hazards models were used to estimate the associations between body mass index , waist circumference , relative weight change , and PA level with incident AF . During follow-up , there were 1775 cases of incident AF . Body mass index and waist circumference were positively associated with AF as was weight loss/gain of > 5 % initial body weight . An ideal level of PA had a small protective effect on AF risk and partially attenuated the risk of AF associated with excess weight in men but not women : compared with men with a normal body mass index , the risk of AF in obese men with an ideal , intermediate , and poor level of PA at baseline was increased by 37 % , 129 % , and 156 % ( Pinteraction=0.04 ) . During follow-up , PA did not modify the association between weight gain and risk of AF . Conclusions —Obesity and extreme weight change are risk factors for incident AF , whereas being physically active is associated with a small reduction in risk . In men only , being physically active offset some , but not all , of the risk incurred with excess body weight BACKGROUND Obese patients have favorable outcomes in congestive heart failure , hypertension , peripheral vascular disease , and coronary artery disease . Obesity also has been linked with increased incidence of atrial fibrillation , but its influence on outcomes in atrial fibrillation patients has not been investigated . The objective of this research is to investigate the effect of obesity on outcomes in atrial fibrillation . METHODS The Atrial Fibrillation Follow-up Investigation of Rhythm Management ( AFFIRM ) study was one of the largest multicenter trials of atrial fibrillation , with 4060 patients . Subjects were r and omized to rate versus rhythm-control strategy . We performed a post hoc analysis of the National Heart , Lung and Blood Institute limited access data set of atrial fibrillation patients who had body mass index ( BMI ) data available in the AFFIRM study . BMI data were not available on 1542 patients . Patients with BMI > or=18.5 were split into normal ( 18.5 - 25 ) , overweight ( 25 - 30 ) , and obese ( > 30 ) categories as per BMI ( kg/m(2 ) ) . Multivariate Cox proportional hazards regression was used on the eligible 2492 patients . End points were all-cause mortality and cardiovascular mortality . RESULTS Over three fourths of all patients in our cohort were overweight or obese . There were 304 deaths ( 103 among normal weight , 108 among overweight , and 93 among obese ) and 148 cardiovascular deaths ( 54 among normal weight , 41 among overweight , and 53 among obese ) over a mean period of 3 years of patient follow-up . On multivariate analysis , overweight ( hazard ratio [ HR ] 0.64 ; 95 % confidence interval [ CI ] , 0.48 - 0.84 ; P=.001 ) and obese ( HR 0.80 ; 95 % CI , 0.68 - 0.93 ; P=.005 ) categories were associated with lower all-cause mortality as compared with normal weight . Overweight ( HR 0.40 ; 95 % CI , 0.26 - 0.60 ; P < .001 ) and obese patients ( HR 0.77 ; 95 % CI , 0.62 - 0.95 ; P=.01 ) also had lower cardiovascular mortality as compared with the normal weight patients . CONCLUSIONS Although in prior studies , obesity has been associated with increased risk of atrial fibrillation , an obesity paradox exists for outcomes in atrial fibrillation . Obese patients with atrial fibrillation appear to have better long-term outcomes than nonobese patients BACKGROUND Japanese patients with atrial fibrillation ( AF ) are generally small and lean , but knowledge of the clinical characteristics of those with low body weight ( LBW : ≤50 kg ) is limited . METHODS AND RESULTS The Fushimi AF Registry is a community-based prospect i ve survey of AF patients who visited the participating medical institutions in Fushmi-ku , Japan . The BW and follow-up data were available for 2,945 patients . We compared the background and the incidence of clinical events during a median follow-up of 746 days between a LBW and non-LBW group . Patients in the LBW group accounted for 26.8 % ( 788 patients ) of the total . The LBW group was more often female , older , and had higher CHADS2score . The incidence of stroke/systemic embolism ( SE ) during follow-up was higher in the LBW group ( hazard ratio ( HR ) : 2.19 , 95 % confidence interval ( CI ) : 1.57 - 3.04 ; P<0.01 ) , whereas that of major bleeding was comparable ( HR : 1.05 , 95 % CI : 0.64 - 1.68 ; P=0.84 ) . This trend was consistently observed in the subgroups stratified by age , sex , and oral anticoagulant prescription at baseline . Multivariate analysis as well as propensity-score matching analysis further supported the significance of LBW as a risk of stroke/SE . CONCLUSIONS Patients in the LBW group had high risk profiles and showed a higher incidence of stroke/SE , but the incidence of major bleeding was not particularly high BACKGROUND The use of warfarin reduces the rate of ischemic stroke in patients with atrial fibrillation but requires frequent monitoring and dose adjustment . Rivaroxaban , an oral factor Xa inhibitor , may provide more consistent and predictable anticoagulation than warfarin . METHODS In a double-blind trial , we r and omly assigned 14,264 patients with nonvalvular atrial fibrillation who were at increased risk for stroke to receive either rivaroxaban ( at a daily dose of 20 mg ) or dose-adjusted warfarin . The per- protocol , as-treated primary analysis was design ed to determine whether rivaroxaban was noninferior to warfarin for the primary end point of stroke or systemic embolism . RESULTS In the primary analysis , the primary end point occurred in 188 patients in the rivaroxaban group ( 1.7 % per year ) and in 241 in the warfarin group ( 2.2 % per year ) ( hazard ratio in the rivaroxaban group , 0.79 ; 95 % confidence interval [ CI ] , 0.6 
    Output:
    