***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 
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    ***EXAMPLES*** 
    Input: OBJECTIVES To assess the optimal stroke prevention treatment for patients with atrial fibrillation ( AF ) and a low-medium risk ( < or = 4 % ) of stroke . DESIGN A total of 668 patients with persistent or permanent AF , without an indication for full dose and with adequate rate control on sotalol , were r and omized to warfarin 1.25 mg + aspirin 75 mg daily ( W/A , 334 patients ) or no anticoagulation ( C , 334 patients ) . The mean follow-up period was 33 months . The protocol intended to verify a 37 % relative risk reduction provided a 4 % stroke incidence in the C group . RESULTS The stroke incidence was less in the W/A group , although the reduction was not statistically significant ( W/A 9.6 % versus C 12.3 % ) . Four haemorrhagic strokes were identified , two in each group . Secondary end-points were transient ischaemic attacks ( TIA ) ( W/A 3.3 % versus C 4.5 % ) , all cause mortality ( W/A 9.3 % versus C 10.8 % ) , cardiovascular morbidity ( W/A 17.7 % versus C 22.2 % ) and the combination of stroke + TIA ( W/A 11.7 % versus C 16.5 % ) . Bleedings were documented in 19 versus four patients ( W/A 5.7 % versus C 1.2 % ) ( P = 0.003 ) , although none fatal . Sinus rhythm ( SR ) was recorded occasionally in 68 patients ( W/A 9.6 % versus C 10.8 % ) . The stroke incidence tended to be higher in those with SR than without , 16.2 % versus 10.4 % . CONCLUSIONS Our results were inconclusive , but consistent with a small beneficial effect of W/A for reduction of stroke and major vascular events in AF patients at moderate risk . The low-dose regiment produced , however , a significantly increased risk of bleedings . Documented SR occasionally recorded may represent a sub population that warrants full dose warfarin 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 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 risk of stroke BACKGROUND Atherosclerotic intracranial arterial stenosis is an important cause of stroke . Warfarin is commonly used in preference to aspirin for this disorder , but these therapies have not been compared in a r and omized trial . METHODS We r and omly assigned patients with transient ischemic attack or stroke caused by angiographically verified 50 to 99 percent stenosis of a major intracranial artery to receive warfarin ( target international normalized ratio , 2.0 to 3.0 ) or aspirin ( 1300 mg per day ) in a double-blind , multicenter clinical trial . The primary end point was ischemic stroke , brain hemorrhage , or death from vascular causes other than stroke . RESULTS After 569 patients had undergone r and omization , enrollment was stopped because of concerns about the safety of the patients who had been assigned to receive warfarin .  During a mean follow-up period of 1.8 years , adverse events in the two groups included death ( 4.3 percent in the aspirin group vs. 9.7 percent in the warfarin group ; hazard ratio for aspirin relative to warfarin , 0.46 ; 95 percent confidence interval , 0.23 to 0.90 ; P=0.02 ) , major hemorrhage ( 3.2 percent vs. 8.3 percent , respectively ; hazard ratio , 0.39 ; 95 percent confidence interval , 0.18 to 0.84 ; P=0.01 ) , and myocardial infa rct ion or sudden death ( 2.9 percent vs. 7.3 percent , respectively ; hazard ratio , 0.40 ; 95 percent confidence interval , 0.18 to 0.91 ; P=0.02 ) . The rate of death from vascular causes was 3.2 percent in the aspirin group and 5.9 percent in the warfarin group ( P=0.16 ) ; the rate of death from nonvascular causes was 1.1 percent and 3.8 percent , respectively ( P=0.05 ) . The primary end point occurred in 22.1 percent of the patients in the aspirin group and 21.8 percent of those in the warfarin group ( hazard ratio , 1.04 ; 95 percent confidence interval , 0.73 to 1.48 ; P=0.83 ) . CONCLUSIONS Warfarin was associated with significantly higher rates of adverse events and provided no benefit over aspirin in this trial . Aspirin should be used in preference to warfarin for patients with intracranial arterial stenosis BACKGROUND Despite the efficacy of warfarin sodium therapy for stroke prevention in atrial fibrillation , many physicians hesitate to prescribe it to elderly patients because of the risk for bleeding complications and because of inconvenience for the patients . METHODS The Second Copenhagen Atrial Fibrillation , Aspirin , and Anticoagulation Study was a r and omized , controlled trial examining the following therapies : warfarin sodium , 1.25 mg/d ; warfarin sodium , 1.25 mg/d , plus aspirin , 300 mg/d ; and aspirin , 300 mg/d . These were compared with adjusted-dose warfarin therapy ( international normalized ratio of prothrombin time [ INR ] , 2.0 - 3.0 ) . Stroke or a systemic thromboembolic event was the primary outcome event . Transient ischemic attack , acute myocardial infa rct ion , and death were secondary events . Data were h and led as survival data , and risk factors were identified using the Cox proportional hazards model . The trial was scheduled for 6 years from May 1 , 1993 , but due to scientific evidence of inefficiency of low-intensity warfarin plus aspirin therapy from another study , our trial was prematurely terminated on October 2 , 1996 . RESULTS We included 677 patients ( median age , 74 years ) . The cumulative primary event rate after 1 year was 5.8 % in patients receiving minidose warfarin ; 7.2 % , warfarin plus aspirin ; 3.6 % , aspirin ; and 2.8 % , adjusted-dose warfarin ( P = .67 ) . After 3 years , no difference among the groups was seen . Major bleeding events were rare . CONCLUSIONS Although the difference was insignificant , adjusted-dose warfarin seemed superior to minidose warfarin and to warfarin plus aspirin after 1 year of treatment . The results do not justify a change in the current recommendation of adjusted-dose warfarin ( INR , 2.0 - 3.0 ) for stroke prevention in atrial fibrillation In patients with chronic nonrheumatic atrial fibrillation , prophylaxis of peripheral arterial embolism is strongly indicated . LMWHs may be an alternative regimen if contraindications for oral anticoagulants are present . In the present study the effect of LMWH on the incidence of embolism in atrial fibrillation has been studied in 75 consecutive patients in comparison to no specific treatment . Patients received one daily injection of the LMWH CY 216 ( n = 35 ) subcutaneously over a period of 6 months . Patients of the control group ( n = 40 ) were observed over the same period of time . In the group treated with CY 216 , three embolic events ( 8.6 % ) occurred , of which two were localized in the cerebrum . One of these two cerebral embolic events was fatal . In the control group , eight embolic events ( 20 % ) occurred , six of these were intracerebral and , of these , five were fatal . An even more pronounced difference between the groups was observed on evaluation of the patients with preceding cerebral embolism . Of 15 patients treated with LMWH  , one extracerebral nonfatal embolism occurred . In the control group three of the seven patients ( 43 % ) experienced fatal reembolism . The results show that in patients with atrial fibrillation one daily subcutaneous injection of LMWH reduces the incidence of arterial embolism to about one third . No adverse effects were observed during the 6-month treatment period with LMWH The Canadian Atrial Fibrillation Anticoagulation Study was a r and omized double-blind placebo-controlled trial to assess the potential of warfarin to reduce systemic thromboembolism and its inherent risk of hemorrhage . As a result of the publication of two other " positive " studies of similar design and objective , this study was stopped early before completion of its planned recruitment of 630 patients . There were 187 patients r and omized to warfarin and 191 to placebo .  Permanent discontinuation of study medication occurred in 26 % of warfarin-treated and 23 % of placebo-treated patients . The target range of the international normalized ratio was 2 to 3 . For the warfarin-treated patients , the international normalized ratio was in the target range 43.7 % of the study days , above it 16.6 % of the study days and below it 39. 
    Output:
    
The observed rates of intracranial and extracranial hemorrhage were not significantly increased by OAC therapy , but the confidence intervals were wide .
Treatment with adjusted-dose warfarin to achieved INRs of 2 to 3 reduces stroke , disabling or fatal stroke , and death for patients with non-valvular AF .
The benefits were not substantially offset by increased bleeding among these participants in r and omized clinical trials .