***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 The use of warfarin sodium for treating venous thromboembolism in patients with cancer is associated with a significant risk of recurrence and bleeding . The use of low-molecular-weight heparin sodium for secondary prevention of venous thromboembolism in cancer patients may reduce the complication rate . OBJECTIVE To determine whether a fixed dose of subcutaneous low-molecular-weight heparin is superior to oral warfarin for the secondary prophylaxis of venous thromboembolism in patients with cancer and venous thromboembolism . METHODS In a r and omized , open-label multicenter trial performed between April 1995 and March 1999 , we compared subcutaneous enoxaparin sodium ( 1.5 mg/kg once a day ) with warfarin given for 3 months in 146 patients with venous thromboembolism and cancer . MAIN OUTCOME MEASURE A combined outcome event defined as major bleeding or recurrent venous thromboembolism within 3 months . RESULTS Of the 71 evaluable patients assigned to receive warfarin , 15 ( 21.1 % ; 95 % confidence interval [ CI ] , 12.3%-32.4 % ) experienced one major outcome event compared with 7 ( 10.5 % ) of the 67 evaluable patients assigned to receive enoxaparin ( 95 % CI , 4.3%-20.3 % ; P = .09 ) . There were 6 deaths owing to hemorrhage in the warfarin group compared with none in the enoxaparin group . In the warfarin group , 17 patients ( 22.7 % ) died ( 95 % CI , 13.8%-33.8 % ) compared with 8 ( 11.3 % ) in the enoxaparin group ( 95 % CI , 5.0%-21.0 % ; P = .07 ) . No difference was observed regarding the progression of the underlying cancer or cancer-related death . CONCLUSIONS These results confirm that warfarin is associated with a high bleeding rate in patients with venous thromboembolism and cancer . Prolonged treatment with low-molecular-weight heparin may be as effective as oral anticoagulants and may be safer in these cancer patients Background Patients with cancer are at increased risk of  venous thromboembolism ( VTE ) and the risk is further elevated after a primary VTE . To reduce the risk of recurrent events , extended prophylaxis with vitamin K antagonists ( VKA ) is available for use . However , in a large r and omized trial ( Comparison of Low-Molecular-Weight Heparin versus Oral Anticoagulant Therapy for the Prevention of Recurrent Venous Thromboembolism in Patients with Cancer [ CLOT ] ; Lee et al ) , extended duration dalteparin reduced the relative risk of recurrent VTE by 52 % compared to VKA ( p=0.002 ) . A recent subgroup analysis of patients with moderate-to-severe renal impairment also revealed lower absolute VTE rates with dalteparin ( 3 % vs. 17 % ; p=0.011 ) . To measure the economic value of dalteparin as an alternative to VKA , a patient-level cost utility analysis was conducted from a Canadian perspective . Methods Re source use data captured during the CLOT trial were extracted and linked to 2015 Canadian unit cost estimates . Health state utilities were then measured using the Time-Trade-Off technique in 24 r and omly selected members of the general Canadian public to estimate the gains in quality -adjusted life years ( QALYs ) . Results For the entire CLOT trial population ( n=676 ) , the dalteparin group had significantly higher mean costs compared to the VKA group ( $ Can5,771 vs. $ Can2,569 ; p<0.001 ) . However , the utility assessment revealed that 21 of 24 respondents ( 88 % ) selected dalteparin over VKA , with an associated gain of 0.14 ( 95 % confidence interval [ CI ] : 0.10–0.18 ) QALYs . When the incremental cost of dalteparin was combined with the QALY gain , dalteparin had a cost of $ Can23,100 ( 95 % CI : $ Can19,200–$Can25,800 ) per QALY gained . The analysis in patients with renal impairment suggested even better economic value with the cost per QALY gained being < $ 14,000 . Conclusion Extended duration dalteparin is a cost-effective alternative to VKA for the prevention of recurrent VTE in patients with cancer , especially in those with renal impairment This study evaluated enoxaparin alone versus initial enoxaparin followed by warfarin in secondary prevention of venous thromboembolic events in adults with active malignancy . Cancer patients ( n = 122 ) with acute symptomatic venous thromboembolic events were r and omly allocated to receive subcutaneous enoxaparin 1.0 mg/kg every 12 hours for 5 days , followed by 1.0 mg/kg daily ( group 1a ) or 1.5 mg/kg daily ( group 1b ) for 175 days , or subcutaneous enoxaparin 1.0 mg/kg every 12 hours for at least 5 days and until a stable international normalized ratio of 2 to 3 was achieved on oral warfarin begun on day 2 and continued to day 180 ( group 2 ) . There were no significant differences in major and minor bleeding rates between treatment groups . No bleeding events were intracranial or fatal .  Enoxaparin treatment was feasible , generally well tolerated , and effective for a 180-day period in the secondary prevention of venous thromboembolic events in patients with active malignancy OBJECTIVE To determine the cost and cost effectiveness of adding venous thromboembolism ( VTE ) prophylaxis with enoxaparin , a low-molecular-weight heparin , to st and ard care for acutely ill , hospitalized medical patients . METHODS A pharmacoeconomic model was developed to simulate the 6- to 14-day course of enoxaparin prophylaxis evaluated in the MEDENOX trial in a US healthcare setting . Clinical results as reported for the trial were applied to re source use and treatment costs in a US healthcare environment . The model projects hospital length of stay and cost for an acute medical admission from a third-party payer perspective , as well as costs for the course of enoxaparin . RESULTS VTE prophylaxis with enoxaparin would account for 1.2 % to 2.4 % of the cost of a hospital admission , with an additional $ 23 + /- $ 28 to $ 99 + /- $ 122 to complete the course of prophylaxis out of hospital . Incremental cost effectiveness of VTE prophylaxis relative to no prophylaxis ranges from $ 1249 to $ 3088 per VTE avoided . Venous thromboembolism prophylaxis appears to be a break-even intervention , with the cost recouped through avoided treatment , if the rate of treated VTE without prophylaxis is at least 3 - 4 % . DISCUSSION AND CONCLUSIONS The MEDENOX trial demonstrated that prophylaxis with enoxaparin substantially decreases the risk of VTE among acutely ill , hospitalized medical patients . Economic analysis indicates that this protection represents a small increase in current treatment costs . Prophylaxis is cost effective in terms of incremental cost per VTE avoided . Furthermore , there is a reasonable likelihood that the cost of prophylaxis will be offset by avoided future VTE treatment Background : In a r and omized trial ( ie , Comparison of Low-Molecular-Weight Heparin versus Oral Anticoagulant Therapy for the Prevention of Recurrent Venous Thromboembolism in Patients with Cancer [ CLOT ] ) that evaluated secondary prophylaxis of recurrent venous thromboembolism ( VTE ) in patients with cancer , dalteparin reduced the relative risk by 52 % compared to oral vitamin K antagonists ( VKAs ; hazard ratio = 0.48 , P = .002 ) . A recent subgroup analysis in patients with moderate to severe renal impairment also revealed lower absolute VTE rates with dalteparin ( 3 % vs 17 % ; P = .011 ) . To measure the economic value of dalteparin in these population s , a pharmacoeconomic analysis was conducted from the Dutch health-care system perspective . Methods : Re source utilization data contained within the CLOT trial data base were extracted and converted into direct cost estimates . Univariate analysis was then conducted to compare the total cost of therapy between patients r and omized to dalteparin or VKA therapy . Health state utilities were then measured in 24 members of the general public using the time trade-off technique . Results : When all of the cost components were combined for the entire population ( n = 676 ) , the dalteparin group had significantly higher overall costs than the VKA control group ( dalteparin = € 2375 vs VKA = € 1724 ; P < .001 ) . However , dalteparin was associated with a gain of 0.14 ( 95 % confidence interval [ CI ] : 0.10 - 0.18 ) quality -adjusted life years ( QALYs ) over VKA . When the incremental cost was combined with the utility gain , dalteparin had a cost of € 4,697 ( 95 % CI : € 3824-€4951 ) per QALY gained . Conclusion : Secondary prophylaxis with dalteparin is a cost-effective alternative to VKA for the prevention of recurrent VTE in patients with cancer OBJECTIVE To evaluate whether low-molecular-weight heparin ( LMWH ) could be equally ( or more ) effective than oral anti-vitamin-K agents ( AVK ) in the long-term treatment of deep venous thrombosis ( DVT ) . DESIGN A r and omised , open-label trial . MATERIAL AND METHODS In this trial , 241 patients with symptomatic proximal DVT of the lower limbs confirmed by duplex ultrasound scan were included . After initial LMWH , patients received 6 months of treatment with full therapeutic dosage of tinzaparin or acenocoumarol . The primary outcome was the 12-month incidence of symptomatic recurrent venous thrombo-embolism ( VTE ) . Duplex scans were performed at 6 and 12 months . RESULTS During the 12-month period , six patients ( 5 % ) of 119 who received LMWH and 13 ( 10.7 % ) of 122 who received AVK had recurrent VTE ( p=0.11 ) . In patients with cancer , recurrent VTE tended to be lower in the LMWH group ( two of 36 [ 5.5 % ] ) vs. seven of 33 [ 21.2 % ] ; p=0.06 ) . One major bleeding occurred in the LMWH group and three in the AVK group . Venous re-canalisation increased significantly at 6 months ( 73.1 % vs. 47.5 % ) and at 12 months ( 91.5 % vs. 69.2 % ) in the LMWH group . CONCLUSIONS Tinzaparin was more effective than AVK in achieving re-canalisation of leg thrombi . Long-term tinzaparin was at least as efficacious and safe as AVK for preventing recurrent VTE , especially in patients with cancer Direct oral anticoagulants may be effective and safe for treatment of venous thromboembolism ( VTE ) in cancer patients , but they have not been compared with low-molecular-weight heparin ( LMWH ) , the current recommended treatment for these patients . The Hokusai VTE-cancer study is a r and omised , open-label , clinical trial to evaluate whether edoxaban , an oral factor Xa inhibitor , is non-inferior to LMWH for treatment of VTE in patients with cancer . We present the rationale and some design features of the study . One such feature is the composite primary outcome of recurrent VTE and major bleeding during a 12-month study period . These two complications occur frequently in cancer patients receiving anticoagulant treatment and have a significant impact . The evaluation beyond six months will fill the current gap in the evidence base for the long-term treatment of these patients . Based on the observation that the risk of recurrent VTE in patients with active cancer is similar to that in those with a history of cancer , the Hokusai VTE-cancer study will enrol patients if whose cancer was diagnosed within the past two years . In addition , patients with incidental VTE are eligible because their risk of recurrent VTE is similar to that in patients with symptomatic disease . The unique design features of the Hokusai VTE-cancer study should lead to enrolment of a broad spectrum of cancer patients with VTE who could benefit from oral anticoagulant treatment 
    Output:
    
Conclusions The totality of high- quality clinical and cost-effectiveness data supports the use of dalteparin over other low-molecular-weight heparins for preventing recurrent venous thromboembolism in patients with cancer