***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 Secondary prevention trials do not distinguish outcomes according to stroke cause . The purpose of the study was to determine whether trial efficacy of anticoagulation for secondary prevention could be replicated in clinical practice in strokes of different etiology . Methods A 2-year observation study was undertaken in 288 stroke patients with atrial fibrillation ( mean age 76 years ; 55 % women ) who were receiving anticoagulation therapy to maintain an international normalized ratio of 2.0 to 3.0 . Comparisons were made of ( 1 ) patient characteristics , anticoagulation control , and annual stroke/hemorrhage rates with those of the European Atrial Fibrillation Trial and ( 2 ) cause of recurrent stroke by initial stroke subtype . Results Subjects were 5 years older ( 95 % CI 3 to 7 years ) , and more patients had  small-vessel stroke ( 26 % versus 14 % ; 95 % CI 3 % to 17 % ) compared with corresponding trial data . The duration spent in the target anticoagulation range ( 55 % versus 59 % ) , recurrent stroke rate ( 5.1 % versus 3.6 % per year ) , and major ( 2.3 % versus 2.2 % per year ) or minor ( 9.5 % versus 11.8 % per year ) hemorrhage rates were comparable with those in patients receiving warfarin  in the r and omized study . Ten of 14 ( 71 % ) of embolic recurrences occurred in patients with a previous cardioembolic episode , and 8 of 11 ( 73 % ) lacunar recurrences occurred in patients with previous lacunar stroke as the qualifying event for anticoagulation ( P = 0.025 ) . Only 3 of 14 cardioembolic compared with 8 of 11 lacunar recurrences occurred during adequate anticoagulation . Conclusions Anticoagulation for secondary stroke prevention in clinical practice achieves outcomes comparable with those of r and omized trials . Nearly 26 % of qualifying strokes and 40 % of recurrences were nonembolic ; stroke subtype should be considered when making treatment decisions Abstract Background : This retrospective study was performed to develop a model to predict the maintenance dosage of the vitamin K antagonist acenocoumarol , based upon the first INR after a st and ard initial dosage regimen . Material and Methods : Out patients with atrial fibrillation ( n = 284 ) and initial regimens of 6 - 4 or 6 - 4 - 2 mg acenocoumarol on day 1 , 2 and 3 , respectively , were included . The maintenance dosage of the period 3–6 months after the instalment was related to the first INR after those st and ard initial dosage regimens , because in that period the INR was 76 % of the time within the therapeutic range and therefore considered suitable to perform the analysis . Results : A clear relation was found between the first INR , the maintenance dosage and the age . A model that predicts the maintenance dosage immediately after the st and ard initial dosage and based on the first INR and adjusted for age , has been developed , according to the formula : required dosage = 5.03 - 1.65 * ln ( first INR ) − 0.01 * age . Conclusion : We have developed a formula to predict the maintenance dosage of acenocoumarol . With this formula it is possible to install this maintenance dosage and thus achieve oral anticoagulant therapy within the therapeutic range at an earlier stage . This will have to be shown in a prospect i ve study Extremely elderly patients are being treated with anticoagulant therapy with increasing frequency . We sought to assess the rates of bleeding in such patients and to carefully examine risk factors that might predict this bleeding . This was a prospect i ve cohort study conducted from 1 January 2007 to 29 February 2008 at an anticoagulation clinic in Modena , Italy . Ninety patients , 90 years or older , among 1635 patients with nonvalvular atrial fibrillation were studied ; 69 ( 77 % ) were women with a median age of 91.71 years ( range 90–98 ) . During the enrolment period , all the patients were interviewed during an ambulatory visit and were followed in the outpatient setting . Hemorrhagic , thromboembolic and fatal events over 1 year of follow-up were monitored . Six ( 7 % ) patients discontinued vitamin K antagonists ( three due to bleeding , two due to noncompliance , two due to physician recommendation ) . Twenty-one ( 23 % ) patients died , and 35 ( 39 % ) were admitted to hospital . One patient had an intracranial hemorrhage [ 1 % , 95 % confidence interval ( CI ) 0.27–6.0 ] , two patients had a major extracranial hemorrhage ( 2 % , 95 % CI 0.7–8.0 ) . One patient had an ischemic stroke ( 1 % , 95 % CI 0.27–6.0 ) , two patients had embolic arterial ischemia ( 2 % , 95 % CI 0.7–8.0 ) . All the events occurred when the international normalized ratio was outside the target range , or after oral anticoagulation had been stopped . In our study of extremely elderly anticoagulated patients , we found low rates of bleeding and thromboembolism . These findings support the use of oral anticoagulants in such patients Background — Tecarfarin ( ATI-5923 ) is a novel oral vitamin K antagonist . Unlike warfarin , it is metabolized by esterases , escaping metabolism by the cytochrome P450 system and thereby avoiding cytochrome P450–mediated drug-drug or drug-food interactions as well as genetic variations found in the cytochrome P450 system . Both tecarfarin and warfarin can be monitored with the international normalized ratio . We hypothesized that the time in therapeutic range for tecarfarin will exceed values usually experienced with warfarin . Methods and Results — This was a 6- to 12-week open-label , multicenter , phase IIA study of 66 atrial fibrillation patients with a mild to moderate risk of stroke to determine the safety and tolerability of tecarfarin and to ascertain an optimal tecarfarin dosing regimen . Sixty-four subjects ( 97 % ) were taking warfarin at enrollment and were switched to tecarfarin . After the initial 3 weeks of tecarfarin treatment , the mean interpolated time in therapeutic range was 71.4 % . Only 10.9 % of patients had time in therapeutic range of < 45 % . Times in extreme international normalized ratio ranges of < 1.5 and > 4.0 were 1.2 % and 1.2 % , respectively . The median daily dose ( for an individual patient ) to maintain an international normalized ratio between 2 and 3 was 15.6 mg ( range , 6 to 29 mg ) . Conclusions — This is the first study of tecarfarin in patients with atrial fibrillation . It appears that tecarfarin may possess advantages over the currently available st and ard of care , warfarin , by improving time in therapeutic range . Adequately powered prospect i ve trials are warranted to definitively compare tecarfarin with warfarin in clinical setting s for which warfarin is indicated The purpose of this study was to establish the safety and efficacy of sodium warfarin in the secondary prophylaxis of venous thrombosis in patients with cancer . This was an inception cohort study of patients enrolled in an anticoagulation clinic between July 1991 and October 1996 . The rates of bleeding and recurrent thrombosis were evaluated in all the patients , and the results in patients with cancer ( n = 104 ) were compared with those without cancer ( n = 208 ) . The rate of major hemorrhage was 0.4 % and 0.3 % per treatment month in the patients with cancer and those without cancer , respectively . The rates of recurrent thrombosis were 1.2 % and 0.2 % per treatment month in the patients with cancer compared with those without cancer , respectively . We conclude that warfarin is safe when used for the secondary prophylaxis of patients with cancer who have had a venous or arterial thrombosis , and the risk of major hemorrhage is not significantly different when compared with the risk in patients without cancer . The rate of recurrent thrombosis is approximately sixfold higher in patients with cancer being treated with warfarin for secondary prophylaxis of thrombosis compared with patients without cancer . Nonetheless , the rate of recurrent thrombosis is not overly excessive , and warfarin can be viewed as a relatively effective form of therapy for these patients 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 Apixaban , an oral factor Xa inhibitor administered in fixed doses , may simplify the treatment of venous thromboembolism . METHODS In this r and omized , double-blind study , we compared apixaban ( at a dose of 10 mg twice daily for 7 days , followed by 5 mg twice daily for 6 months ) with conventional therapy ( subcutaneous enoxaparin , followed by warfarin ) in 5395 patients with acute venous thromboembolism . The primary efficacy outcome was recurrent symptomatic venous thromboembolism or death related to venous thromboembolism . The principal safety outcomes were major bleeding alone and major bleeding plus clinical ly relevant nonmajor bleeding . RESULTS The primary efficacy outcome occurred in 59 of 2609 patients ( 2.3 % ) in the apixaban group , as compared with 71 of 2635 ( 2.7 % ) in the conventional-therapy group ( relative risk , 0.84 ; 95 % confidence interval [ CI ] , 0.60 to 1.18 ; difference in risk [ apixaban minus conventional therapy ] , -0.4 percentage points ; 95 % CI , -1.3 to 0.4 ) . Apixaban was noninferior to conventional therapy ( P<0.001 ) for predefined upper limits of the 95 % confidence intervals for both relative risk ( < 1.80 ) and difference in risk ( < 3.5 percentage points ) . Major bleeding occurred in 0.6 % of patients who received apixaban and in 1.8 % of those who received conventional therapy ( relative risk , 0.31 ; 95 % CI , 0.17 to 0.55 ; P<0.001 for superiority ) . The composite outcome of major bleeding and clinical ly relevant nonmajor bleeding occurred in 4.3 % of the patients in the apixaban group , as compared with 9.7 % of those in the conventional-therapy group ( relative risk , 0.44 ; 95 % CI , 0.36 to 0.55 ; P<0.001 ) . Rates of other adverse events were similar in the two groups . CONCLUSIONS A fixed-dose regimen of apixaban alone was noninferior to conventional therapy for the treatment of acute venous thromboembolism and was associated with significantly less bleeding ( Funded by Pfizer and Bristol-Myers Squibb ; Clinical Trials.gov number , NCT00643201 ) CONTEXT When unfractionated heparin is used to treat acute venous thromboembolism , it is usually administered by intravenous infusion with coagulation monitoring , which requires hospitalization . However , subcutaneous administration of fixed-dose , weight-adjusted , unfractionated heparin may be suitable for inpatient and outpatient treatment 
    Output:
    
A trend towards studies reporting greater numbers of VKA control measures over time was observed over our review time horizon , particularly , with AF and observational studies