***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 and Purpose — Intracranial hemorrhage is the most devastating complication of anticoagulation . Outcomes associated with different sites of intracranial bleeding occurring with warfarin versus dabigatran have not been defined . Methods — Analysis of 18 113 participants with atrial fibrillation in the R and omized Evaluation of Long-term anticoagulant therapY ( RE-LY ) trial assigned to adjusted-dose warfarin ( target international normalized ratio , 2–3 ) or dabigatran ( 150 mg or 110 mg , both twice daily ) . Results — During a mean of 2.0 years of follow-up ,  154 intracranial hemorrhages occurred in 153 participants : 46 % intracerebral ( 49 % mortality ) , 45 % subdural ( 24 % mortality ) , and 8 % subarachnoid ( 31 % mortality ) . The rates of intracranial hemorrhage were 0.76 % , 0.31 % , and 0.23 % per year among those assigned to warfarin , dabigatran 150 mg , and dabigatran 110 mg , respectively ( P<0.001 for either dabigatran dose versus warfarin ) . Fewer fatal intracranial hemorrhages occurred among those assigned dabigatran 150 mg and 110 mg ( n=13 and n=11 , respectively ) versus warfarin ( n=32 ; P<0.01 for both ) . Fewer traumatic intracranial hemorrhages occurred among those assigned to dabigatran ( 11 patients with each dose ) compared with warfarin ( 24 patients ; P<0.05 for both dabigatran doses versus warfarin ) . Independent predictors of intracranial hemorrhage were assignment to warfarin ( relative risk , 2.9 ; P<0.001 ) , aspirin use ( relative risk , 1.6 ; P=0.01 ) , age ( relative risk , 1.1 per year ; P<0.001 ) , and previous stroke/transient ischemic attack ( relative risk , 1.8 ; P=0.001 ) . Conclusions — The clinical spectrum of intracranial hemorrhage was similar for patients given warfarin and dabigatran . Absolute rates at all sites and both fatal and traumatic intracranial hemorrhages were lower with dabigatran than with warfarin . Concomitant aspirin use was the most important modifiable independent risk factor for intracranial hemorrhage Background and Purpose — Patients with atrial fibrillation and previous ischemic stroke (IS)/transient ischemic attack ( TIA ) are at high risk of recurrent cerebrovascular events despite anticoagulation . In this prespecified subgroup analysis , we compared warfarin with edoxaban in patients with versus without previous IS/TIA . Methods — ENGAGE AF-TIMI 48 ( Effective Anticoagulation With Factor Xa Next Generation in Atrial Fibrillation-Thrombolysis in Myocardial Infa rct ion 48 ) was a double-blind trial of 21 105 patients with atrial fibrillation r and omized to warfarin ( international normalized ratio , 2.0–3.0 ; median time-in-therapeutic range , 68.4 % ) versus once-daily edoxaban ( higher-dose edoxaban regimen [ HDER ] , 60/30 mg ; lower-dose edoxaban regimen , 30/15 mg ) with 2.8-year median follow-up . Primary end points included all stroke/systemic embolic events ( efficacy ) and major bleeding ( safety ) . Because only HDER is approved , we focused on the comparison of HDER versus warfarin . Results — Of 5973 ( 28.3 % ) patients with previous IS/TIA , 67 % had CHADS2 ( congestive heart failure , hypertension , age , diabetes , prior stroke/transient ischemic attack ) > 3 and 36 % were ≥75 years . Compared with 15 132 without previous IS/TIA , patients with previous IS/TIA were at higher risk of both thromboembolism and bleeding ( stroke/systemic embolic events 2.83 % versus 1.42 % per year ; P<0.001 ; major bleeding 3.03 % versus 2.64 % per year ; P<0.001 ; intracranial hemorrhage , 0.70 % versus 0.40 % per year ; P<0.001 ) . Among patients with previous IS/TIA , annualized intracranial hemorrhage rates were lower with HDER than with warfarin ( 0.62 % versus 1.09 % ; absolute risk difference , 47 [ 8–85 ] per 10 000 patient-years ; hazard ratio , 0.57 ; 95 % confidence interval , 0.36–0.92 ; P=0.02 ) . No treatment subgroup interactions were found for primary efficacy ( P=0.86 ) or for intracranial hemorrhage ( P=0.28 ) . Conclusions — Patients with atrial fibrillation with previous IS/TIA are at high risk of recurrent thromboembolism and bleeding . HDER is at least as effective and is safer than warfarin , regardless of the presence or the absence of previous IS or TIA . Clinical Trial Registration — URL : http://www . clinical trials.gov . Unique identifier : NCT00781391 BACKGROUND Specific reversal agents for non-vitamin K antagonist oral anticoagulants are lacking . Idarucizumab , an antibody fragment , was developed to reverse the anticoagulant effects of dabigatran . METHODS We undertook this prospect i ve cohort study to determine the safety of 5 g of intravenous idarucizumab and its capacity to reverse the anticoagulant effects of dabigatran in patients who had serious bleeding ( group A ) or required an urgent procedure ( group B ) . The primary end point was the maximum percentage reversal of the anticoagulant effect of dabigatran within 4 hours after the administration of idarucizumab , on the basis of the determination at a central laboratory of the dilute thrombin time or ecarin clotting time . A key secondary end point was the restoration of hemostasis . RESULTS This interim analysis included 90 patients who received idarucizumab ( 51 patients in group A and 39 in group B ) . Among 68 patients with an elevated dilute thrombin time and 81 with an elevated ecarin clotting time at baseline , the median maximum percentage reversal was 100 % ( 95 % confidence interval , 100 to 100 ) . Idarucizumab normalized the test results in 88 to 98 % of the patients , an effect that was evident within minutes . Concentrations of unbound dabigatran remained below 20 ng per milliliter at 24 hours in 79 % of the patients . Among 35 patients in group A who could be assessed , hemostasis , as determined by local investigators , was restored at a median of 11.4 hours . Among 36 patients in group B who underwent a procedure , normal intraoperative hemostasis was reported in 33 , and mildly or moderately abnormal hemostasis was reported in 2 patients and 1 patient , respectively . One thrombotic event occurred within 72 hours after idarucizumab administration in a patient in whom anticoagulants had not been reinitiated . CONCLUSIONS Idarucizumab completely reversed the anticoagulant effect of dabigatran within minutes . ( Funded by Boehringer Ingelheim ; RE-VERSE AD Clinical Trials.gov number , NCT02104947 . ) Background Idarucizumab , a monoclonal antibody fragment , was developed to reverse the anticoagulant effect of dabigatran . Methods We performed a multicenter , prospect i ve , open‐label study to determine whether 5 g of intravenous idarucizumab would be able to reverse the anticoagulant effect of dabigatran in patients who had uncontrolled bleeding ( group A ) or were about to undergo an urgent procedure ( group B ) . The primary end point was the maximum percentage reversal of the anticoagulant effect of dabigatran within 4 hours after the administration of idarucizumab , on the basis of the diluted thrombin time or ecarin clotting time . Secondary end points included the restoration of hemostasis and safety measures . Results A total of 503 patients were enrolled : 301 in group A , and 202 in group B. The median maximum percentage reversal of dabigatran  was 100 % ( 95 % confidence interval , 100 to 100 ) , on the basis of either the diluted thrombin time or the ecarin clotting time . In group A , 137 patients ( 45.5 % ) presented with gastrointestinal bleeding and 98 ( 32.6 % ) presented with intracranial hemorrhage ; among the patients who could be assessed , the median time to the cessation of bleeding was 2.5 hours . In group B , the median time to the initiation of the intended procedure was 1.6 hours ; periprocedural hemostasis was assessed as normal in 93.4 % of the patients , mildly abnormal in 5.1 % , and moderately abnormal in 1.5 % . At 90 days , thrombotic events had occurred in 6.3 % of the patients in group A and in 7.4 % in group B , and the mortality rate was 18.8 % and 18.9 % , respectively . There were no serious adverse safety signals . Conclusions In emergency situations , idarucizumab rapidly , durably , and safely reversed the anticoagulant effect of dabigatran . ( Funded by Boehringer Ingelheim ; RE‐VERSE AD Clinical Trials.gov number , NCT02104947 . 
    Output:
    
CONCLUSIONS Non-vitamin K oral anticoagulants halve the risk of fatal ICH in patients with non-valvular atrial fibrillation compared with VKAs , whereas indirect comparisons indicate that NOAC-specific reversal agents may be associated with a lower case fatality rate in NOAC-related ICH