***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 Antithrombotic therapy can prevent strokes and transient ischemic attacks ( TIAs ) in carefully selected patients who have chronic nonvalvular atrial fibrillation ( NVAF ) . Our objectives were 3-fold : to document the use of warfarin and aspirin therapy in Missouri Medicare beneficiaries with chronic NVAF ; to identify factors associated with warfarin and aspirin underuse ; and to determine the association between prescription of warfarin and aspirin at hospital discharge and adverse outcomes in this elderly , frail population . METHODS We linked chart review s from all Missouri hospitals to Medicare cl aims data from 1993 to 1996 . From chart review s , we documented Medicare beneficiaries ' demographic factors , comorbid conditions , and antithrombotic therapy prescribed at the time of hospital discharge . From Medicare cl aims , we determined the date of outcomes -death from any cause or hospitalization for an ischemic event ( a stroke , a TIA , or a myocardial infa rct ion ) . RESULTS Only 328 ( 55 % ) of the 597 Medicare beneficiaries were prescribed antithrombotic therapy at hospital discharge : 34 % received warfarin and 21 % received aspirin . Advanced age , female gender , and rural residency predicted underuse of antithrombotic therapy . After controlling for these factors , as well as stroke risk factors and contraindications to anticoagulation , the prescription of warfarin was associated with a 24 % relative risk reduction ( RRR ) in adverse outcomes ( P=0.003 ) . Prescription of aspirin was associated with a nonsignificant 5 % RRR in these events ( P=0.56 ) . CONCLUSIONS The underuse of antithrombotic therapy in Medicare beneficiaries who have NVAF is associated with measurable adverse outcomes . The benefit of warfarin therapy may extend to frail , elderly patients , a group that was excluded from r and omized controlled trials . The role of antiplatelet therapy in this population deserves further study because many of these patients have relative contraindications to warfarin Abstract Objective : To investigate the effectiveness of aspirin and coumarin in preventing thromboembolism in patients with non-rheumatic atrial fibrillation in general practice . Design : R and omised controlled trial . Participants : 729 patients aged ≥60 years with atrial fibrillation , recruited in general practice , who had no established indication for coumarin . Mean age was 75 years and mean follow up 2.7 years . Setting : Primary care in the Netherl and s. Interventions : Patients eligible for st and ard intensity coumarin ( international normalised ratio 2.5 - 3.5 ) were r and omly assigned to st and ard anticoagulation , very low intensity coumarin ( international normalised ratio 1.1 - 1.6 ) , or aspirin ( 150 mg/day ) ( stratum 1 ) . Patients ineligible for st and ard anticoagulation were r and omly assigned to low anticoagulation or aspirin ( stratum 2 ) . Main outcome measures : Stroke , systemic embolism , major haemorrhage , and vascular death . Results : 108 primary events occurred ( annual event rate 5.5 % ) , including 13 major haemorrhages ( 0.7 % a year ) . The hazard ratio was 0.91 ( 0.61 to 1.36 ) for low anticoagulation versus aspirin and 0.78 ( 0.34 to 1.81 ) for st and ard anticoagulation versus aspirin . Non-vascular death was less common in the low anticoagulation group than in the aspirin group ( 0.41 , 0.20 to 0.82 ) . There was no significant difference between the treatment groups in bleeding incidence . High systolic and low diastolic blood pressure and age were independent prognostic factors . Conclusion : In a general practice population ( without established indications for coumarin ) neither low nor st and ard intensity anticoagulation is better than aspirin in preventing primary outcome events . Aspirin may therefore be the first choice in patients with atrial fibrillation in general practice . Key messages Studies have shown that patients with non-rheumatic atrial fibrillation may benefit from anticoagulation This study in a general practice population found no benefit of st and ard or low dose anticoagulation on risk of stroke , systemic embolism , major haemorrhage , or vascular death when compared with aspirin Hypertension and age were prognostic factors for event occurrence Aspirin is the treatment of choice for preventing thromboembolism in primary care patients at low A system has been constructed to evaluate the design , implementation , and analysis of  r and omized control trials ( RCT ) . The degree of quadruple blinding ( the r and omization process , the physicians and patients as to therapy , and the physicians as to ongoing results ) is considered to be the most important aspect of any trial . The analytic techniques are scored with the same emphasis as is placed on the control of bias in the planning and implementation of the studies . Description of the patient and treatment material s and the measurement of various controls of quality have less weight . An index of quality of a RCT is proposed with its pros and cons . If published papers were to approximate these principles , there would be a marked improvement in the quality of r and omized control trials . Finally , a reasonable st and ard design and conduct of trials will facilitate the interpretation of those with conflicting results and help in making valid combinations of undersized trials 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 BACKGROUND A number of studies have demonstrated the efficacy of oral anticoagulant therapy in reducing the risk of stroke and systemic embolism in patients with nonrheumatic atrial fibrillation . However , both the targeted and the actual levels of anticoagulation differed widely among the studies , and a number of studies failed to report st and ardized prothrombin-time ratios as international normalized ratios ( INRs ) . We therefore performed an analysis to determine the intensity of oral anticoagulant therapy in nonrheumatic atrial fibrillation that provides the best balance between the prevention of thromboembolism and the occurrence of bleeding complications . METHODS We calculated INR-specific incidence rates for both ischemic and major hemorrhagic events occurring in 214 patients who received anticoagulant therapy in the European Atrial Fibrillation Trial , a secondary -prevention trial in patients with nonrheumatic atrial fibrillation and a recent episode of minor cerebral ischemia . RESULTS The optimal intensity of anticoagulation was found to lie between an INR of 2.0 and an INR of 3.9 . No treatment effect was apparent with anticoagulation below an INR of 2.0 . The rate of thromboembolic events was lowest at INRs from 2.0 to 3.9 , and most major bleeding complications occurred with treatment at intensities with INRs of 5.0 or above . CONCLUSIONS To achieve optimal levels of anticoagulation with the lowest risk in patients with atrial fibrillation and a recent episode of cerebral ischemia , the target value for the INR should be set at 3.0 , and values below 2.0 and above 5.0 should be avoided BACKGROUND AND PURPOSE The optimal intensity of warfarin therapy for secondary prevention of stroke in nonvalvular atrial fibrillation ( NVAF ) remains unclear . We studied the efficacy and safety of conventional- and low-intensity warfarin therapy in a prospect i ve , r and omized , multicenter trial . METHODS The study population consisted of patients with NVAF ( < 80 years old ) who had a stroke or transient ischemic attack . The patients were r and omly allocated into a conventional-intensity group ( international normalized ratio [ INR ] 2.2 to 3.5 ) and a low-intensity group ( INR 1.5 to 2.1 ) . They were carefully monitored , and the annual rate of recurrent ischemic stroke and major hemorrhagic complications were compared between the groups . RESULTS We enrolled 115 patients ( mean age 66.7+/-6.5 years ) into the study . Fifty-five and 60 patients were allocated into the conventional- and low-intensity groups , respectively . The trial was stopped after a follow-up of 658+/-423 days , when major hemorrhagic complications occurred in 6 patients of the conventional-intensity group and the frequency ( 6.6 % per year ) was significantly higher than that in the low-intensity group ( 0 % per year , P=0.01 , Fisher 's exact test ) . All of the 6 patients with major bleeding were elderly ( mean age 74 years ) , and their mean  INR  before the major hemorrhage was 2.8 . The annual rate of ischemic stroke was low in both groups ( 1.1 % per year in the conventional-intensity group and 1.7 % per year in the low-intensity groups ) and did not differ significantly . CONCLUSIONS For secondary prevention of stroke in persons with NVAF , especially in old patients , the low-intensity warfarin ( INR 1.5 to 2 . 1 ) treatment seems to be safer than the conventional-intensity ( INR 2.2 to 3.5 ) treatment Background Atrial fibrillation in the absence of rheumatic valvular disease is associated with a fivefold to sevenfold increased risk of ischemic stroke . Methods and Main Results . The Stroke Prevention in Atrial Fibrillation Study , a multicenter , r and omized trial , compared 325 mg/day aspirin ( double-blind ) or warfarin with placebo for prevention of ischemic stroke and systemic embolism ( primary events ) , and included 1,330 in patients and out patients with constant or intermittent atrial fibrillation . During a mean follow-up of 1.3 years , the rate of primary events in patients assigned to placebo was 6.3 % per year and was reduced by 42 % in those assigned to aspirin ( 3.6 % per year , p = 0.02 ; 95 % confidence interval , 9–63 % ) . In the subgroup of  warfarin-eligible patients ( most less than 76 years old ) , warfarin dose-adjusted to prolong prothrombin time to 1.3-fold to 1.8-fold that of control reduced the risk of primary events by 67 % ( warfarin versus placebo , 2.3 % versus 7.4 % per year , p = 0.01 ; 95 % confidence interval , 27–85 % ) . Primary events or death were reduced 58 % ( p = 0.01 ) by warfarin and 32 % ( p = 0.02 ) by aspirin . The risk of significant bleeding was 1.5 % , 1.4 % , and 1.6%o per year in patients assigned to warfarin , aspirin , and placebo , respectively . Conclusions Aspirin and warfarin are both effective in reducing ischemic stroke and systemic embolism in patients with atrial fibrillation . Because warfarin-eligible patients composed a subset of all aspirin-eligible patients , the magnitude of reduction in events by warfarin versus aspirin can not be compared . Too few events occurred in warfarin-eligible patients to directly assess the relative benefit of aspirin compared with warfarin , and the trial is continuing to address this issue . Patients with nonrheumatic atrial fibrillation who can safely take either aspirin or warfarin should receive prophylactic antithrombotic therapy to reduce the 
    Output:
    
Low-dose warfarin or low-dose warfarin with aspirin was less efficacious for stroke prevention than adjusted-dose warfarin .
REVIEW ER 'S CONCLUSIONS The evidence strongly supports warfarin in AF for patients at average or greater risk of stroke , although clearly there is a risk of hemorrhage .
Although not definitively supported by the evidence , aspirin may prove to be useful for stroke prevention in sub-groups with a low risk of stroke , with less risk of hemorrhage than with warfarin .