***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 
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    ***EXAMPLES*** 
    Input: Background — The R and omized Evaluation of Long-Term Anticoagulation Therapy ( RE-LY ) trial compared dabigatran 110 mg BID ( D110 ) and 150 mg BID ( D150 ) with warfarin for stroke prevention in 18 113 patients with nonvalvular atrial fibrillation . Methods and Results — Cardioversion on r and omized treatment was permitted . Precardioversion transesophageal echocardiography was encouraged , particularly in dabigatran-assigned patients . Data from before , during , and 30 days after cardioversion were analyzed . A total of 1983 cardioversions were performed in 1270 patients : 647 , 672 , and 664 in the D110 , D150 , and warfarin groups , respectively . For D110 , D150 , and warfarin , transesophageal echocardiography was performed before 25.5 % , 24.1 % , and 13.3 % of cardioversions , of which 1.8 % , 1.2 % , and 1.1 % were positive for left atrial thrombi . Continuous treatment with study drug for ≥3 weeks before cardioversion was lower in D110 ( 76.4 % ) and D150 ( 79.2 % ) compared with warfarin ( 85.5 % ; P<0.01 for both ) . Stroke and systemic embolism rates at 30 days were 0.8 % , 0.3 % , and 0.6 % ( D110 versus warfarin , P=0.71 ; D150 versus warfarin , P=0.40 ) and similar in patients with and without transesophageal echocardiography . Major bleeding rates were 1.7 % , 0.6 % , and 0.6 % ( D110 versus warfarin , P=0.06 ; D150 versus warfarin , P=0.99 ) . Conclusions — This study is the largest cardioversion experience to date and the first to evaluate a novel anticoagulant in this setting . The frequencies of stroke and major bleeding within 30 days of cardioversion on the 2 doses of dabigatran were low and comparable to those on warfarin with or without transesophageal echocardiography guidance . Dabigatran is a reasonable alternative to warfarin in patients requiring cardioversion . Clinical Trial Registration — URL : http://www . Clinical Trials.gov . Unique identifier : NCT00262600 In 2013 , the European Heart Rhythm Association ( EHRA ) published a Practical Guide on the use of non-VKA oral anticoagulants ( NOACs ) in patients with atrial fibrillation ( AF ) ( Heidbuchel H , Verhamme P , Alings M , Antz M , Hacke W , Oldgren J , Sinnaeve P , Camm AJ , Kirchhof P , European Heart Rhythm A. European Heart Rhythm Association Practical Guide on the use of new oral anticoagulants in patients with non-valvular atrial fibrillation . Europace 2013;15:625 - 651 ; Heidbuchel H , Verhamme P , Alings M , Antz M , Hacke W , Oldgren J , Sinnaeve P , Camm AJ , Kirchhof P. EHRA practical guide on the use of new oral anticoagulants in patients with non-valvular atrial fibrillation : executive summary . Eur Heart J 2013;34:2094 - 2106 ) . The document received widespread interest , not only from cardiologists but also from neurologists , geriatricians , and general practitioners , as became evident from the distribution of > 350 000 copies of its pocket version ( the EHRA Key Message Booklet ) world-wide . Since 2013 , numerous new studies have appeared on different aspects of NOAC therapy in AF patients . Therefore , EHRA up date d the Practical Guide , including new information but also providing balanced guiding in the many areas where prospect i ve data are still lacking . The outline of the original guide that addressed 15 clinical scenarios has been preserved , but all chapters have been rewritten . Main changes in the Up date comprise a discussion on the definition of ' non-valvular AF ' and eligibility for NOAC therapy , inclusion of finalized information on the recently approved edoxaban , tailored dosing information dependent on concomitant drugs , and /or clinical characteristics , an exp and ed chapter on neurologic scenarios ( ischaemic stroke or intracranial haemorrhage under NOAC ) , an up date d anticoagulation card and more specifics on start-up and follow-up issues . There are also many new flow charts , like on appropriate switching between anticoagulants ( VKA to NOAC or vice versa ) , default scenarios for acute management of coronary interventions , step-down schemes for long-term combined antiplatelet-anticoagulant management in coronary heart disease , management of bleeding , and cardioversion under NOAC therapy . The Up date d Guide is available in full in EP Europace ( Heidbuchel H , Verhamme P , Alings M , Antz M , Diener HC , Hacke W , Oldgren J , Sinnaeve P , Camm AJ , Kirchhof P , Advisors . Up date d European Heart Rhythm Association Practical Guide on the use of  non-vitamin K antagonist anticoagulants  in patients with non-valvular atrial fibrillation . Europace 2015;17:1467 - 1507 ) , while additional re sources can be found at the related ESC/EHRA website ( www.NOACforAF.eu ) Abstract Aim The primary objective was to compare apixaban to heparin/vitamin K antagonist ( VKA ) in patients with atrial fibrillation ( AF ) and ≤48 h anticoagulation prior to r and omization undergoing cardioversion . Methods One thous and five hundred patients were r and omized . The apixaban dose of 5 mg b.i.d . was reduced to 2.5 mg b.i.d . in patients with two of the following : age ≥ 80 years , weight ≤ 60 kg , or serum creatinine ≥ 133 µmol/L. To expedite cardioversion , at the discretion of the investigator , imaging and /or a loading dose of 10 mg ( down-titrated to 5 mg ) was allowed . The endpoints for efficacy were stroke , systemic embolism ( SE ) , and death . The endpoints for safety were major bleeding and clinical ly relevant non-major ( CRNM ) bleeding . Results There were 1038 active and 300 spontaneous cardioversions ; 162 patients were not cardioverted . Imaging was performed in 855 patients , and 342 received a loading dose of apixaban . Comparing apixaban to heparin/VKA in the full analysis set , there were 0/753 vs. 6/747 strokes [ relative risk ( RR ) 0 ; 95 % confidence interval ( 95 % CI ) 0–0.64 ; nominal P = 0.015 ] , no SE , and 2 vs. 1 deaths ( RR 1.98 ; 95 % CI 0.19–54.00 ; nominal P > 0.999 ) . In the safety population , there were 3/735 vs. 6/721 major ( RR 0.49 ; 95 % CI 0.10–2.07 ; nominal P = 0.338 ) and 11 vs. 13 CRNM bleeding events ( RR 0.83 ; 95 % CI 0.34–1.89 ; nominal P = 0.685 ) . On imaging , 60/61 with thrombi continued r and omized treatment ; all ( 61 ) were without outcome events . Conclusions Rates of strokes , systemic emboli , deaths , and bleeds were low for both apixaban and heparin/VKA treated AF patients undergoing cardioversion . Clinical Trials.gov number 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 Dabigatran etexilate , a direct thrombin inhibitor and non-vitamin K antagonist oral anticoagulant ( NOAC ) , has been shown to effectively prevent thromboembolic events in patients with non-valvular atrial fibrillation ( AF ) . However , there is a paucity of data on the antithrombotic efficacy and safety of dabigatran in the resolution of left atrial appendage ( LAA ) thrombi in AF patients . Objective The primary objective of the RE-LATED AF trial is to assess whether dabigatran results in a faster complete LAA thrombus resolution as compared to vitamin K antagonist phenprocoumon . Secondary objectives are to assess the impact of dabigatran on complete LAA thrombus resolution rate within 6 weeks of treatment and change in LAA thrombus volume under treatment . Furthermore , this study aims to assess and compare safety and tolerability of dabigatran vs. phenprocoumon . Methods The study is design ed as a prospect i ve , r and omized , open-label , controlled , explorative , blinded endpoint ( PROBE ) trial . Patients with AF and left atrial appendage thrombus confirmed by transoesophageal echocardiography ( TEE ) will be r and omized to receive either dabigatran ( 150 mg bid ) or phenprocoumon ( INR 2–3 ) for the resolution of LAA thrombus formation for at least 21 days . Thrombus resolution will be determined by TEE 3 weeks after treatment initiation and subsequently at weeks 4 and 6 , if the LAA thrombus has not been resolved before . A total of 110 patients are planned to be r and omized . Conclusion This is the first prospect i ve , multicentre , r and omized controlled clinical trial investigating safety and efficacy of a NOAC for the resolution of LAA thrombi in patients with non-valvular AF 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 
    Output:
    
Conclusions The findings of this meta- analysis suggest that NOACs are similar to VKAs regarding the frequency of LA/LAA thrombus in patients with AF .