***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: IMPORTANCE Despite the frequency of  atrial fibrillation ( AF )  in clinical practice , relatively little is known about sex differences in symptoms and quality of life and how they may affect treatment and outcomes . OBJECTIVE To determine whether symptoms , quality of life , treatment , and outcomes differ between women and men with AF . DESIGN , SETTING , AND PARTICIPANTS This observational cohort study included 10 135 patients with AF . The Outcomes Registry for Better Informed Treatment of Atrial Fibrillation is a prospect i ve , nationwide , multicenter outpatient registry of patients with incident and prevalent AF enrolled at 176 sites between June 2010 and August 2011 . MAIN OUTCOMES AND MEASURES Symptoms , quality of life as measured by Atrial Fibrillation Effects on Quality of Life scores , AF treatment , cardiovascular outcomes , stroke or non- central nervous system embolism , and all-cause mortality . RESULTS Overall , 4293 of the cohort ( 42 % ) were female . Compared with men , women were older ( 77 years ; interquartile range [ IQR ] , 69 - 83 , vs 73 years ; IQR , 65 - 80 ; P < .001 ) and had higher median CHA2DS2-VASc scores ( 5 ; IQR , 4 - 6 , vs 3 ; IQR , 2 - 5 ; P < .001 ) , but less sleep apnea ( 578 [ 13.5 % ] vs 1264 [ 21.6 % ] ; P < .001 ) . Only 32.1 % of women ( n = 1378 ) were asymptomatic ( European Heart Rhythm Association class I ) compared with 42.5 % of men ( n = 2483 ) in unadjusted analyses ( P < .001 ) . Women had lower ( more severe ) unadjusted baseline overall Atrial Fibrillation Effects on Quality of Life scores ( n = 2007 ; 80 ; IQR , 62 - 92 vs 83 ; IQR , 69 - 94 ; P < .001 ) . Women had similar rates of anticoagulation and similar time in therapeutic range . In follow-up , women experienced lower risk-adjusted all-cause mortality ( adjusted hazard ratio , 0.57 ; 95 % CI , 0.49 - 0.67 ) and cardiovascular death ( adjusted hazard ratio , 0.56 ; 95 % CI , 0.44 - 0.72 ) ; however , they had a higher risk for stroke or non- central nervous system embolism ( adjusted hazard ratio , 1.39 ; 95 % CI , 1.05 - 1.84 ; P = .02 ) compared with men . CONCLUSIONS AND RELEVANCE Women with AF have more symptoms and worse quality of life . Despite higher risk , women have lower risk-adjusted all-cause and cardiovascular death compared with men , but higher stroke rates . Future studies should focus on how treatment and interventions specifically affect AF-related quality of life and cardiovascular outcomes in women . TRIAL REGISTRATION clinical trials.gov Identifier : NCT01165710 Left ventricular hypertrophy ( LVH ) is significantly related to adverse clinical outcomes in patients at high risk of cardiovascular events . In patients with atrial fibrillation ( AF ) , data on LVH , that is , prevalence and determinants , are inconsistent mainly because of different definitions and heterogeneity of study population s. We determined echocardiographic-based LVH prevalence and clinical factors independently associated with its development in a prospect i ve cohort of patients with non-valvular ( NV ) AF . From the " Atrial Fibrillation Registry for Ankle-brachial Index Prevalence Assessment : Collaborative Italian Study " ( ARAPACIS ) population , 1,184 patients with NVAF ( mean age 72 ± 11 years ; 56 % men ) with complete data to define LVH were selected . ARAPACIS is a multicenter , observational , prospect i ve , longitudinal on-going study design ed to estimate prevalence of peripheral artery disease in patients with NVAF . We found a high prevalence of LVH ( 52 % ) in patients with NVAF . Compared to those without LVH , patients with AF with LVH were older and had a higher prevalence of hypertension , diabetes , and previous myocardial infa rct ion ( MI ) . A higher prevalence of ankle-brachial index ≤0.90 was seen in patients with LVH ( 22 vs 17 % , p = 0.0392 ) . Patients with LVH were at significantly higher thromboembolic risk , with CHA2DS2-VASc ≥2 seen in 93 % of LVH and in 73 % of patients without LVH ( p < 0.05 ) . Women with LVH had a higher prevalence of concentric hypertrophy than men ( 46 % vs 29 % , p = 0.0003 ) . Logistic regression analysis demonstrated that female gender ( odds ratio [ OR ] 2.80 , p < 0.0001 ) , age ( OR 1.03 per year , p < 0.001 ) , hypertension ( OR 2.30 , p < 0.001 ) , diabetes ( OR 1.62 , p = 0.004 ) , and previous MI ( OR 1.96 , p = 0.001 ) were independently associated with LVH . In conclusion , patients with NVAF have a high prevalence of LVH , which is related to female gender , older age , hypertension , and previous MI . These patients are at high thromboembolic risk and deserve a holistic approach to cardiovascular prevention 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 —Previous studies provide conflicting results about whether women are at higher risk than men for thromboembolism in the setting of atrial fibrillation ( AF ) . We examined data from a large contemporary cohort of AF patients to address this question . Methods and Results —We prospect ively studied 13 559 adults with AF and recorded data on patients ’ clinical characteristics and the occurrence of incident hospitalizations for ischemic stroke , peripheral embolism , and major hemorrhagic events through search ing vali date d computerized data bases and medical record review . We compared event rates by patient sex using multivariable log-linear regression , adjusting for clinical risk factors for stroke , and stratifying by warfarin use . We identified 394  ischemic stroke and peripheral embolic events during 15 494 person-years of follow-up off warfarin . After multivariable analysis , women had higher annual rates of thromboembolism off warfarin than did men ( 3.5 % versus 1.8 % ; adjusted rate ratio [ RR ] , 1.6 ; 95 % CI , 1.3 to 1.9 ) . There was no significant difference by sex in 30-day mortality after thromboembolism ( 23 % for both ) . Warfarin use was associated with significantly lower adjusted thromboembolism rates for both women and men ( RR , 0.4 ; 95 % CI , 0.3 to 0.5 ; and RR , 0.6 ; 95 % CI , 0.5 to 0.8 , respectively ) , with similar annual rates of major hemorrhage ( 1.0 % and 1.1 % , respectively ) . Conclusions —Women are at higher risk than men for AF-related thromboembolism off warfarin . Warfarin therapy appears be as effective in women , if not more so , than in men , with similar rates of major hemorrhage . Female sex is an independent risk factor for thromboembolism and should influence the decision to use anticoagulant therapy in persons with AF AIMS The risk of stroke is greater among women with atrial fibrillation ( AF ) than men .  Warfarin protects against stroke , but treatment-related bleeding occurs more often in women than in men . METHODS AND RESULTS SPORTIF III ( open label , n=3410 ) and V ( double-blind , n=3922 ) included 2257 women with AF and one or more stroke risk factors r and omized to warfarin [ target international normalized ratio ( INR ) 2.0 - 3.0 ] or ximelagatran ( 36 mg twice daily ) . Primary outcomes were all stroke ( ischaemic/haemorrhagic ) and systemic embolic event .  Women were older , on average , than men , 73.4+/-8.0 vs. 69.8+/-9.0 years ( P<0.0001 ) . More women were > 75-years old and women had more risk factors than men had ( P<0.0001 ) . The INR on warfarin ( mean 2.5+/-0.7 ) was within target range for 67 % of follow-up regardless of gender . Women more often developed primary events [ 2.08%/year , 95 % confidence interval ( CI ) 1.60 - 2.56%/year vs. 1.44%/year , 95 % CI 1.18 - 1.71%/year in men ; P=0.016 ) . Major bleeding rates were similar ( P=0.766 ) but women experienced more overall ( major/minor ) bleeding ( P<0.001 ) . Warfarin was associated with more overall bleeding in both genders and more major bleeding in women than in men ( P=0.001 ) . CONCLUSION When compared with men with AF , women in these studies were older and had more stroke risk factors . Women were more prone to anticoagulant-related bleeding ; the higher rate of thrombo-embolism among women was related to more frequent interruption of anticoagulant therapy BACKGROUND The use of warfarin reduces the rate of ischemic stroke in patients with atrial 
    Output:
    
Meta‐ analysis from NOAC trials found a differential effect of NOACs  , with male patients being more protected from stroke/SEE and female patients more protected from major bleeding events .