***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 Treatment with warfarin sodium is effective for stroke prevention in atrial fibrillation but many physicians hesitate to prescribe it to elderly patients presumably because of the associated risk for bleeding and the inconvenience of frequent blood tests for the patients . METHODS In the Second Copenhagen Atrial Fibrillation , Aspirin , and Anticoagulation ( AFASAK 2 ) Study , we studied the rate of bleeding events associated with the incidence of thromboembolic events in patients receiving warfarin sodium , 1.25 mg/d ; warfarin sodium , 1.25 mg/d , plus aspirin , 300 mg/d ; aspirin , 300 mg/d ; or adjusted-dose warfarin therapy aim ing at an international normalized ratio of the prothrombin time ratio ( INR ) of 2.0 to 3.0 . The study was scheduled for 6 years from May 1 , 1993 , but owing to evidence of inefficiency of low-intensity therapy plus aspirin from another study it was prematurely terminated on October 2 , 1996 . Minor and major bleeding events were recorded prospect ively . The rate of bleeding was calculated using the Kaplan-Meier method and risk factors were identified by the Cox proportional hazards model . RESULTS Of 677 included patients , 130 ( median age , 77 years ; range , 67 - 89 years ) experienced bleeding . One woman and 12 men experienced major bleeding . Four had intracranial bleeding : 2 cases were fatal and 2 were nonfatal . During treatment with mini-dose warfarin , warfarin plus aspirin , aspirin , and adjusted-dose warfarin , the annual rate of major bleeding was 0.8 % , 0.3 % , 1.4 % , and 1.1 % , respectively ( P = .20 ) . After 3 years of treatment the cumulative rate of any bleeding was 24.7 % , 24.4 % , 30.0 % , and 41.1 % ( P = .003 ) , respectively . Increasing INRvalue ( P<.001 ) and prior myocardial infa rct ion ( P = .001 ) were independent risk factors for bleeding , whereas increasing age was not . CONCLUSIONS Fixed mini-dose warfarin and aspirin alone or in combination were associated with both minor and major bleeding . The small number of major bleeding events in patients receiving adjusted-dose warfarin therapy as compared with those receiving less intensive antithrombotic treatments and the finding of no significant influence of age on the risk for bleeding indicate that even elderly patients with atrial fibrillation tolerate adjusted-dose warfarin therapy ( INR , 2.0 - 3.0 ) OBJECTIVE This study was performed to characterize the risk of stroke in elderly patients with recurrent intermittent atrial fibrillation ( AF ) . BACKGROUND Although intermittent AF is common , relatively little is known about the attendant risk of stroke . METHODS A longitudinal cohort study was performed comparing 460 participants with intermittent AF with 1,552 with sustained AF treated with aspirin in the Stroke Prevention in Atrial Fibrillation studies and followed for a mean of two years . Independent risk factors for ischemic stroke were identified by multivariate analysis . RESULTS Patients with intermittent AF were , on average , younger ( 66 vs. 70 years , p < 0.001 ) , were more often women ( 37 % vs. 26 % p < 0.001 ) and less often had heart failure ( 11 % vs. 21 % , p < 0.001 ) than those with sustained AF . The annualized rate of ischemic stroke was similar for those with intermittent ( 3.2 % ) and sustained AF ( 3.3 % ) . In patients with intermittent AF , independent predictors of ischemic stroke were advancing age ( relative risk [ RR ] = 2.1 per decade , p < 0.001 ) , hypertension ( RR = 3.4 , p = 0.003 ) and prior stroke ( RR = 4.1 , p = 0.01 ) . Of those with intermittent AF predicted to be high risk ( 24 % ) , the observed stroke rate was 7.8 % per year ( 95 % confidence interval 4.5 to 14 ) . CONCLUSIONS In this large cohort of AF patients given aspirin , those with intermittent AF had stroke rates similar to patients with sustained AF and similar stroke risk factors . Many elderly patients with recurrent intermittent AF have substantial rates of stroke and likely benefit from anticoagulation . High-risk patients with intermittent AF can be identified using the same clinical criteria that apply to patients with sustained AF Background — Oral anticoagulation ( OAC ) therapy is effective in atrial fibrillation but requires vigilance to maintain the international normalized ratio in the therapeutic range . This report examines how differences in time in therapeutic range ( TTR ) between centers and between countries affect the outcomes of OAC therapy . Methods and Results — In a posthoc analysis , the TTRs of patients on OAC in a r and omized trial of OAC versus clopidogrel plus aspirin  ( Atrial Fibrillation Clopidogrel Trial With Irbesartan for Prevention of Vascular Events [ ACTIVE W ] ) were used to calculate the mean TTR  for each of 526 centers and 15 countries . Proportional-hazards analysis , with and without adjustment for baseline variables , was performed , with patients stratified by TTR quartile and country . A wide variation in TTRs was found between centers , with mean TTRs for centers in the 4 quartiles of 44 % , 60 % , 69 % , and 78 % . For patients at centers below the median TTR ( 65 % ) , no treatment benefit was demonstrated as measured by relative risk for vascular events of clopidogrel plus aspirin versus OAC ( relative risk , 0.93 ; 95 % confidence interval , 0.70 to 1.24 ; P=0.61 ) . However , for patients at centers with a TTR above the study median , OAC had a marked benefit , reducing vascular events by > 2-fold ( relative risk , 2.14 ; 95 % confidence interval , 1.61 to 2.85 ; P<0.0001 ) . Mean TTR also varied between countries from 46 % to 78 % ; relative risk ( clopidogrel plus aspirin versus OAC ) varied from 0.6 to 3.6 ( a 5-fold difference ) . A population -average model predicted that a TTR of 58 % would be needed to be confident that patients would benefit from being on OAC . Conclusions — A wide variation exists in international normalized ratio control , as measured by TTR , between clinical centers and between countries , which has a major impact on the treatment benefit of OAC therapy . For centers and countries , a target threshold TTR exists ( estimated between 58 % and 65 % ) below which there appears to be little benefit of OAC over antiplatelet therapy BACKGROUND AND PURPOSE The most common stroke subtype among atrial fibrillation ( AF ) patients not receiving anticoagulants is cardioembolic . In the SPORTIF III and V trials , the oral direct thrombin inhibitor ximelagatran was as effective as warfarin in reducing the risk of stroke in patients with nonvalvular AF . We assessed any differential effect of warfarin versus ximelagatran on the risk and outcome of cardioembolic and noncardioembolic stroke . METHODS 7329 patients with AF and > or = 1 risk factors for stroke were r and omized to treatment with warfarin ( target international normalized ratio 2.0 - -3.0 ) or fixed-dose ximelagatran . Strokes were classified into specific subtypes . Therapeutic effect of warfarin and ximelagatran , adverse events , and stroke outcomes were assessed according to stroke subtype . RESULTS The annual stroke rate was low for both cardioembolic ( ximelagatran , 0.39 % ; warfarin , 0.47 % ) and noncardioembolic stroke ( ximelagatran , 0.57 % ; warfarin , 0.37 % ) . In ischemic strokes , 33.9 % ( ximelagatran ) and 34.3 % ( warfarin ) had strokes of presumed cardioembolic origin . When fatal stroke , disabling stroke , myocardial infa rct ion , and death from any cause were combined as poor outcome , patients with cardioembolic strokes had the highest rate of poor outcome ( 40 % ) but this was non- significant . CONCLUSIONS In SPORTIF III and V the efficacy of warfarin and ximelagatran were similar for prevention of cardioembolic and noncardioembolic strokes . Overall outcome tended to be worse following cardioembolic stroke . Ximelagatran has been withdrawn from the market due to hepatic side effects , but similar compounds are presently being studied OBJECTIVES This trial evaluated the efficacy and safety of the combination of antiplatelet and moderate-intensity anticoagulation therapy in patients with atrial fibrillation associated with recognized risk factors or mitral stenosis . BACKGROUND Warfarin was more effective than aspirin in preventing stroke in these patients ; combined therapy with low anticoagulant intensity was ineffective . Mitral stenosis patients were not investigated . METHODS We performed a multicenter r and omized trial in 1,209 patients at risk . The intermediate-risk group included patients with risk factors or age > 60 years : 242 received the cyclooxygenase inhibitor triflusal  , 237 received  acenocumarol , and 235 received a combination of both .  The high-risk group included patients with prior embolism or mitral stenosis : 259 received anticoagulants and 236 received the combined therapy . Median follow-up was 2.76 years . Primary outcome was a composite of vascular death and nonfatal stroke or systemic embolism . RESULTS Primary outcome was lower in the combined therapy than in the anticoagulant arm in both the intermediate- ( hazard ratio [ HR ] 0.33 [ 95 % confidence interval (CI)0.12 to 0.91 ] ; p = 0.02 ) and the high-risk group ( HR 0.51 [ 95 % CI 0.27 to 0.96 ] ; p = 0.03 ) . Primary outcome plus severe bleeding was lower with combined therapy in the intermediate-risk group . Nonvalvular and mitral stenosis patients had similar embolic event rates during anticoagulant therapy . CONCLUSIONS The combined antiplatelet plus moderate-intensity anticoagulation therapy significantly decreased the vascular events compared with anticoagulation alone and proved to be safe in atrial fibrillation patients BACKGROUND AND PURPOSE Nonvalvular atrial fibrillation ( AF ) is a strong , independent risk factor for stroke , but the absolute rate of stroke varies widely among AF patients , importantly influencing the potential benefit of antithrombotic prophylaxis . We explore factors associated with ischemic stroke in AF patients taking aspirin .  METHODS We performed multivariate logistic regression analysis of 2012 participants given aspirin alone or in combination with low , inefficacious doses of warfarin in the Stroke Prevention in Atrial Fibrillation I-III trials followed for a mean of 2.0 years , during which 130 ischemic strokes were observed . RESULTS Age ( relative risk [RR]=1.8 per decade , P<0.001 ) , female sex ( RR=1.6 , P=0.01 ) , history of hypertension ( RR=2.0 , P<0.001 ) , systolic blood pressure > 160 mm Hg ( RR=2.3 , P<0.001 ) , and prior stroke or transient ischemic attack ( RR=2.9 , P<0.001 ) were independently associated with increased stroke risk . Regular consumption of > /=14 alcohol-containing drinks per week was associated with reduced stroke risk ( adjusted RR=0.4 , P=0.04 ) . Among SPAF III participants , estrogen hormone replacement therapy was associated with a higher risk of ischemic stroke ( adjusted RR=3.2 , P=0.007 ) . With the use of these variables , a risk stratification scheme for primary prevention separated participants into those with high ( 7.1%/y , 22 % of the cohort ) , moderate ( 2.6%/y , 37 % of the cohort ) , and low ( 0.9%/y , 41 % of the cohort ) rates of stroke . Ischemic strokes in low-risk participants were less often disabling ( P<0.001 ) . CONCLUSIONS Patients with AF who have high and low rates of stroke during treatment with  aspirin can be identified . However , validation of our risk stratification scheme is necessary before it can be applied with confidence to clinical management . Postmenopausal estrogen replacement therapy and moderate alcohol consumption may additionally modify the risk of stroke in AF , but these findings require confirmation Reports of bleeding complications of medical therapy should be based on valid methods of classification , but the reproducibility of existing methods has not been tested . Therefore , we prospect ively studied three methods to classify the severity of bleeding : a purely subjective implicit method , a previously published explicit method using brief criteria , and the bleeding severity index , which is a new explicit method using detailed criteria about the amount , rate , and consequences of bleeding . Three physicians independently review ed abstract s of 168 patients treated with anticoagulants .  The proportion of cases classified as major bleeding varied widely when the implicit method was used ( 2 , 
    Output:
    
There was conflicting evidence regarding rates of major adverse events consisting of composite end points , although event rates were generally low .
This systematic review suggests that there is still insufficient evidence to advocate a clear benefit of the addition of APT to ACT compared with ACT alone in reducing the risk of vascular events in a population of patients at high risk of TEs result ing from AF .