***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: Objective To do an indirect comparison analysis of apixaban against dabigatran etexilate ( 2 doses ) and rivaroxaban ( 1 dose ) , as well as of rivaroxaban against dabigatranetexilate ( 2 doses ) , for their relative efficacy and safety against each other , with particular focus on the secondary prevention population for stroke prevention in atrial fibrillation . A secondary objective was to do the same analysis in the primary prevention cohort . Design Indirect treatment comparisons of phase III clinical trials of stroke prevention in atrial fibrillation , with a focus on the secondary prevention cohorts . A secondary analysis was done on the primary prevention cohort . Data sources Medline and Central ( up to June 2012 ) , clinical trials registers , conference proceedings , and websites of regulatory agencies . Study selection R and omised controlled trials of rivaroxaban , dabigatran , or apixaban compared with warfarin for stroke prevention in atrial fibrillation . Results In the secondary prevention ( previous stroke ) subgroup , when apixaban was compared with dabigatran ( 110 mg and 150 mg twice daily ) for efficacy and safety endpoints , the only significant difference seen was less myocardial infa rct ion ( hazard ratio 0.39 , 95 % confidence interval 0.16 to 0.95 ) with apixaban compared with dabigatran 150 mg twice daily . No significant differences were seen in efficacy and most safety endpoints between apixaban or dabigatran 150 mg twice daily versus rivaroxaban . Less haemorrhagic stroke ( hazard ratio 0.15 , 0.03 to 0.66 ) , vascular death ( 0.64 , 0.42 to 0.99 ) , major bleeding ( 0.68 , 0.47 to 0.99 ) , and intracranial bleeding ( 0.27 , 0.10 to 0.73 ) were seen with dabigatran 110 mg twice daily versus rivaroxaban . In the primary prevention ( no previous stroke ) subgroup , apixaban was superior to dabigatran 110 mg twice daily for disabling or fatal stroke ( hazard ratio 0.59 , 0.36 to 0.97 ) . Compared with dabigatran 150 mg twice daily , apixaban was associated with more stroke ( hazard ratio 1.45 , 1.01 to 2.08 ) and with less major bleeding ( 0.75 , 0.60 to 0.94 ) , gastrointestinal bleeding ( 0.61 , 0.42 to 0.89 ) , and other location bleeding ( 0.74 , 0.58 to 0.94 ) . Compared with rivaroxaban , dabigatran 110 mg twice daily was associated with more myocardial infa rct ion events . No significant differences were seen for the main efficacy and safety endpoints between dabigatran 150 mg twice daily and rivaroxaban , or in efficacy endpoints between apixaban and rivaroxaban . Apixaban was associated with less major bleeding ( hazard ratio 0.61 , 0.48 to 0.78 ) than rivaroxaban . Conclusions For secondary prevention , apixaban , rivaroxaban , and dabigatran had broadly similar efficacy for the main endpoints , although the endpoints of haemorrhagic stroke , vascular death , major bleeding , and intracranial bleeding were less common with dabigatran 110 mg twice daily than with rivaroxaban . For primary prevention , the three drugs showed some differences in relation to efficacy and bleeding . These results are hypothesis generating and should be confirmed in a head to head r and omised trial The primary objective of this study was to compare the safety of four fixed-dose regimens of edoxaban with warfarin in patients with non-valvular atrial fibrillation ( AF ) . In this 12-week , parallel-group , multicentre , multinational study , 1,146 patients with AF and risk of stroke were r and omised to edoxaban 30 mg qd , 30 mg bid , 60 mg qd , or 60 mg bid or warfarin dose-adjusted to a target international normalised ratio of 2.0 - 3.0 . The study was double-blind to edoxaban dose , but open-label to warfarin . Primary outcomes were occurrence of major and /or clinical ly relevant non-major bleeding and elevated hepatic enzymes and /or bilirubin .  Mean age was 65 + /- 8.7 years and 64.4 % were warfarin-naïve . Whereas major plus clinical ly relevant non-major bleeding occurred in 3.2 % of patients r and omised to warfarin , the incidence of bleeding was significantly higher with the edoxaban 60 mg bid ( 10.6 % ; p=0.002 ) and 30 mg bid regimens ( 7.8 % ; p=0.029 ) , but not with the edoxaban 60 mg qd ( 3.8 % ) or 30 mg qd regimens ( 3.0 % ) . For the same total daily dose of 60 mg , both bleeding frequency and trough edoxaban concentrations were higher in the 30-mg bid group than in the 60-mg qd group . There were no significant differences in hepatic enzyme elevations or bilirubin values among the groups . The safety profiles  of edoxaban 30 and 60 mg qd in patients with AF were similar to warfarin . In contrast , the edoxaban bid regimens were associated with more bleeding than warfarin . These results suggest that in this three-month study , edoxaban 30 or 60 mg qd are safe and well-tolerated BACKGROUND Atrial fibrillation is an important cause of morbidity and mortality worldwide , but scant data are available for long-term outcomes in individuals outside North America or Europe , especially in primary care setting s. METHODS We did a cohort study using a prospect i ve registry of patients in 47 countries who presented to a hospital emergency department with atrial fibrillation or atrial flutter as a primary or secondary diagnosis . 15 400 individuals were enrolled to determine the occurrence of death and strokes ( the primary outcomes ) in this cohort over eight geographical regions ( North America , western Europe , and Australia ; South America ; eastern Europe ; the Middle East and Mediterranean crescent ; sub-Saharan Africa ; India ; China ; and southeast Asia ) 1 year after attending the emergency department . Patients from North America , western Europe , and Australia were used as the reference population , and compared with patients from the other seven regions FINDINGS Between Dec 24 , 2007 , and Oct 21 , 2011 , we enrolled 15 400 individuals to the registry . Follow-up was complete for 15 361 ( 99·7 % ) , of whom 1758 ( 11 % ) died within 1 year . Fewer deaths occurred among patients presenting to the emergency department with a primary diagnosis of atrial fibrillation compared with patients who had atrial fibrillation as a secondary diagnosis ( 377 [ 6 % ] of 6825 patients vs 1381 [ 16 % ] of 8536 , p<0·0001 ) . Twice as many patients had died by 1 year in South America ( 192 [ 17 % ] of 1132 ) and Africa ( 225 [ 20 % ] of 1137 ) compared with North America , western Europe , and Australia ( 366 [ 10 % ] of 3800 , p<0·0001 ) . Heart failure was the most common cause of death ( 519 [ 30 % ] of 1758 ) ; stroke caused 148 ( 8 % ) deaths . 604 ( 4 % ) of 15361 patients had had a stroke by 1 year ; 170 ( 3 % ) of 6825 for whom atrial fibrillation was a primary diagnosis and 434 ( 5 % ) of 8536 for whom it was a secondary diagnosis ( p<0·0001 ) . The highest number of strokes occurred in patients in Africa ( 89 [ 8 % ] of 1137 ) , China ( 143 [ 7 % ] of 2023 ) , and southeast Asia ( 88 [ 7 % ] of 1331 ) and the lowest occurred in India ( 20 [ < 1 % ] of 2536 ) . 94 ( 3 % ) of 3800 patients in North America , western Europe , and Australia had a stroke . INTERPRETATION Marked unexplained inter-regional variations in the occurrence of stroke and mortality suggest that factors other than clinical variables might be important . Prevention of death from heart failure should be a major priority in the treatment of atrial fibrillation . FUNDING Boehringer Ingelheim Edoxaban is an oral , reversible , direct factor Xa inhibitor in phase III clinical development for the prevention of stroke in atrial fibrillation ( AF ) . A phase II study was undertaken to evaluate the safety and efficacy of edoxaban in Asian patients with non-valvular AF with CHADS2 score ≥1 . In a multicentre , active-controlled , double-blind edoxaban and open-label warfarin , parallel-group study , a total of 235 patients from four Asian countries were r and omly assigned to edoxaban 30 mg qd , 60 mg qd or warfarin dose adjusted to international normalised ratio of 2 - 3 for three months . The primary endpoint was the incidence of central ly adjudicated all bleeding events ( major , clinical ly relevant non-major and minor ) . Secondary endpoints included thromboembolic events , biomarkers of thrombus formation and all adverse events ( AEs ) . The incidence of all bleeding events ( 95 % CI ) was 20.3 % ( 12.9 , 30.4 ) for edoxaban 30 mg , 23.8 % ( 15.8 , 34.1 ) for edoxaban 60 mg , and 29.3 % ( 20.2 , 40.4 ) for warfarin . A subgroup analysis suggested low body weight ( ≤60 kg ) may affect the incidence of bleeding  events with edoxaban . The incidence of study drug-related AEs was 22 % for edoxaban 30 mg , 29 % for edoxaban 60 mg and 33 % for warfarin . No thromboembolic events occurred in any treatment group . In conclusion , this phase II study found a trend for a reduction in the incidence of all bleeding events in Asian AF patients  with edoxaban 30 mg and 60 mg compared with warfarin . Adverse events were similar between the edoxaban 60-mg and warfarin groups and were lower with the edoxaban 30-mg group Flaws in the design , conduct , analysis , and reporting of r and omised trials can cause the effect of an intervention to be underestimated or overestimated . The Cochrane Collaboration ’s tool for assessing risk of bias aims to make the process clearer and more OBJECTIVE To investigate whether warfarin is more effective and superior to aspirin for the prevention of  thromboembolism in nonvalvular atrial fibrillation in Chinese . METHODS In a multicenter r and omized trial , the patients diagnosed as nonvalvular atrial fibrillation were r and omized to receive aspirin 150 mg - 160 mg once daily or adjusted-dose warfarin ( international normalized ratio , 2.0 - 3.0 ) . We compared the effect of the two therapy on the primary end point of ischemic stroke or death from any cause and on the combined end-point ( stroke , death , peripheral arteries embolism , TIA , acute myocardial infa rct ion , serious bleeding ) during a median follow-up period of 19 months . RESULTS Of the 704 patients , 420 ( 59.7 % ) were male . The average patient age was ( 63.3 + /- 9.9 ) years . The median follow-up period is 19 months . The mean dose of warfarin was ( 3.2 + /- 0.7 ) mg . Compared with aspirin , the primary end point of death or ischemic stroke was reduced by warfarin ( 2.7 % vs 6.0 % , P = 0.03 , OR 0.44 , 95 % CI 0.198 - 0.960 ) and the relative risk decreased by 56 % . The thromboembolism event in the aspirin group was significantly higher than that in warfarin group ( 10.6 % vs 5.4 % , P = 0.01 , OR 0.48 , 95 % CI 0.269 - 0.858 ) . There was no significant differences of the mortality rate between the two groups ( 1.2 % vs 2.2 % , P > 0.05 ) . The secondary end point was nonsignificantly reduced in warfarin group than that in aspirin group , while the combined end point is statistically decreased by adjusted-dose warfarin ( 8.4 % vs 13.0 % , P = 0.047 ) . Warfarin treatment was associated with increased bleeding rate compared to aspirin ( 6.9 % vs 2.4 % , P < 0.05 ) , although the major bleeding rate is rather low ( 1.5 % ) . All the major bleeding events occurred with INR above 3.0 . CONCLUSIONS R and omized control study demonstrated that anticoagulation with adjusted- 
    Output:
    
The risk of all‐cause mortality was lower with all DOACs than with warfarin .
The risk of intracranial bleeding was substantially lower for most DOACs compared with warfarin , whereas the risk of gastrointestinal bleeding was higher with some DOACs than warfarin .
Apixaban 5 mg twice daily was ranked the highest for most outcomes , and was cost effective compared with warfarin .
The network meta‐ analysis informs the choice of DOACs for prevention of stroke in patients with atrial fibrillation .
Several DOACs are of net benefit compared with warfarin .