***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 . ) OBJECTIVES This study assessed the feasibility of implanting a device in the left atrial appendage ( LAA ) in patients with atrial fibrillation ( AF ) to prevent thromboembolic stroke . BACKGROUND Meta-analyses confirmed that in cases of left atrial thrombus in nonrheumatic AF patients approximately 90 % of them are in the LAA . METHODS The WATCHMAN Left Atrial Appendage System ( Atritech Inc. , Plymouth , Minnesota ) is a nitinol device implanted percutaneously to seal the LAA . Patients were followed by clinical and transesophageal echocardiography at 45 days and 6 months with annual clinical follow-up thereafter . RESULTS Sixty-six patients underwent device implantation . Mean follow-up was 740 + /- 341 days . At 45 days , 93 % ( 54 of 58 ) devices showed successful sealing of LAA according to protocol . Two patients experienced device embolization , both successfully retrieved percutaneously . No embolizations occurred in 53 patients enrolled after modification of fixation barbs . There were 2 cardiac tamponades , 1 air embolism , and 1 delivery wire fracture ( first generation ) with surgical explantation but no long-term sequelae for the patient . Four patients developed a flat thrombus layer on the device at 6 months that resolved with additional anticoagulation . Two patients experienced transient ischemic attack , 1 without visible thrombus . There were 2 deaths , neither device related . Autopsy documented a stable , fully endothelialized device 9 months after implantation . No strokes occurred during follow-up despite > 90 % of patients with discontinuation of anticoagulation . CONCLUSIONS Preliminary data suggest LAA occlusion with the WATCHMAN System to be safe and feasible . A r and omized study is ongoing comparing oral anticoagulation with percutaneous closure BACKGROUND Currently , 2 different left atrial appendage ( LAA ) closure systems are available for stroke prevention in nonvalvular atrial fibrillation but comparative data are lacking . OBJECTIVES To prospect ively compare procedural data and patient outcome for 2 contemporary LAA closure systems and to investigate an alternative antithrombotic treatment regimen in high-risk patients . METHODS Patients with nonvalvular atrial fibrillation , with high risk for stroke , and who either had contraindication or were not willing to accept oral anticoagulation were prospect ively enrolled . Watchman ( Boston Scientific , Natick , MA ; group A ) or Amplatzer Cardiac Plug ( St Jude Medical , Minneapolis , MN ; group B ) devices were implanted . All patients received antithrombotic therapy for 6 weeks . After repeat transesophageal echocardiography , patients were switched to aspirin . RESULTS Eighty patients were enrolled . There was no statistical difference in patient characteristics in groups A and B : CHA2DS2VASC score : 4.1 ± 1.5 versus 4.5 ± 1.8 ; HASBLED score : 3.1 ± 1.1 versus 3.1 ± 1.1 , respectively . LAA closure was achieved in 78 of 80 patients ( 98 % ) ( group A : 38 of 40 [ 95 % ] vs group B : 40 of 40 [ 100 % ] ) . There was no difference in procedure time ( group A : 48 ± 16 minutes vs group B : 47 ± 15 minutes ; P = .69 ) and fluoroscopy time ( group A : 6.0 ± 4.7 minutes vs group B : 7.3 ± 4.4 minutes ; P = .25 ) . Major complications included 1 air embolism and delayed tamponade in each group . After 6 weeks , 1 device dislodgment and 4 device-related thrombi were detected . Ninety-four percent of the patients ( 73 of 77 ) were switched to aspirin after 6 weeks . During a median follow-up of 364 days ( Q1-Q3 : 283 - 539 days ) , no systemic embolism occurred , but 3 patients died ( heart failure : n = 2 ; bleeding : n = 1 ) . CONCLUSIONS Implantation of both LAA closure devices can be performed with high success rates in high-risk patients . Postprocedural 6 weeks antithrombotic therapy followed by aspirin therapy needs to be confirmed in a larger study BACKGROUND Atrial fibrillation ( AF ) is the most common sustained cardiac arrhythmia and it is associated with an increased stroke risk , due mainly to cardiac embolism from the left atrial appendage ( LAA ) . Percutaneous LAA closure is a method to reduce stroke risk in AF without using anticoagulant agents . In this study we report data from an Italian experience with the LAA occluder Amplatzer Cardiac Plug ( ACP ) device ( Aga Medical Corporation , Plymouth , MN , USA ) . METHODS The study was design ed to evaluate the safety of LAA closure using ACP and the efficacy of the procedure in preventing strokes during a 1-year follow-up . Patients with permanent or paroxysmal AF , high stroke risk , and contraindication to warfarin therapy were selected for the procedure . RESULTS The LAA closure was attempted in 37 patients and succeeded in 34 cases ( 91.9 % ) . Four patients experienced serious complications ( one cardiac tamponade requiring pericardiocentesis , two device embolizations , one low-rate response AF requiring artificial pacing ) . During a 1-year follow-up , ischemic stroke occurred in one of 34 patients , result ing in a stroke rate of 2.94 % ; thus there was a stroke rate reduction of 50.2 % and 26.5 % compared to the expected stroke rate , according to CHADS2 and CHA2 DS2 VASc score . None of the patients who received ACP experienced major bleeding during the follow-up . CONCLUSION LAA closure using ACP is a relatively feasible procedure which can be performed by highly experienced operators to reduce stroke rate in patients with AF , high stroke risk , and contraindication to oral anticoagulants OBJECTIVES The purpose of this study was to assess the safety and efficacy of left atrial appendage ( LAA ) closure in nonvalvular atrial fibrillation ( AF ) patients ineligible for warfarin therapy . BACKGROUND The PROTECT AF ( Watchman Left Atrial Appendage System for Embolic Protection in Patients With Atrial Fibrillation ) trial demonstrated that LAA closure with the Watchman device ( Boston Scientific , Natick , Massachusetts ) was noninferior to warfarin therapy . However , the PROTECT AF trial only included patients who were c and i date s for warfarin , and even patients r and omly assigned to the LAA closure arm received concomitant warfarin  for 6 weeks after Watchman implantation . METHODS A multicenter , prospect i ve , nonr and omized study was conducted of LAA closure with the Watchman device in 150 patients with nonvalvular AF and CHADS₂ ( congestive heart failure , hypertension , age ≥75 years , diabetes mellitus 
    Output:
    
Although superiority of LAAO over NOACs was not demonstrated by RCTs in terms of stroke prevention , LAAO was found to be consistently associated with a lower rate of both thromboembolic and hemorrhagic events as compared with NOACs in observational studies