***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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    Input: Venous thromboembolism ( VTE ) has a significant impact on healthcare costs but is largely preventable with anticoagulant prophylaxis using low-molecular-weight heparins ( LMWHs ) , such as enoxaparin or dalteparin . Rivaroxaban and dabigatran etexilate are two new oral anticoagulants ( NOACs ) both compared with enoxaparin in separate trials . A decision analytic model with a healthcare and national payer perspective over a five-year time horizon was used to evaluate the cost-effectiveness of the NOACs for VTE prophylaxis after total hip replacement ( THR ) or total knee replacement ( TKR ) in France , Italy and Spain .  Efficacy and safety data were obtained from r and omised controlled trials of rivaroxaban vs enoxaparin and an indirect statistical comparison for rivaroxaban vs dabigatran . Rivaroxaban demonstrated dominance across all comparisons , indications and countries . In THR , total per-patient costs were reduced by up to € 160 in the enoxaparin comparison and € 115 in the dabigatran comparison , respectively . In addition , quality -adjusted life-years ( QALYs ) were increased by up to 0.0011 and 0.0012 in each comparison , respectively . Similarly , total costs were reduced in TKR by up to € 137 and € 28 in the enoxaparin and dabigatran comparisons , respectively . The total number of QALYs was increased by up to 0.0014 in the enoxaparin comparison and 0.0005 in the dabigatran comparison . The results were driven by costs since the incremental benefits were minimal . Rivaroxaban use could result in substantial healthcare cost savings and improved quality of life . The results are applicable across three European countries with differing healthcare systems so , potentially , could be generalised to a much wider population BACKGROUND After hip replacement surgery , prophylaxis following discharge from hospital is recommended to reduce the risk of venous thromboembolism . Our aim was to assess the oral , direct thrombin inhibitor dabigatran etexilate for such prophylaxis . METHODS In this double-blind study , we r and omised 3494 patients undergoing total hip replacement to treatment for 28 - 35 days with dabigatran etexilate 220 mg ( n=1157 ) or 150 mg ( 1174 ) once daily , starting with a half-dose 1 - 4 h after surgery ,  or subcutaneous enoxaparin  40 mg once  daily  ( 1162 ) , starting the evening before surgery . The primary efficacy outcome was the composite of total venous thromboembolism ( venographic or symptomatic ) and death from all causes during treatment . On the basis of the absolute difference in rates of venous thromboembolism with enoxaparin versus placebo , the non-inferiority margin for the difference in rates of thromboembolism was defined as 7.7 % . Efficacy analyses were done by modified intention to treat . This trial is registered with Clinical Trials.gov , number NCT00168818 . FINDINGS Median treatment duration was 33 days . 880 patients in the dabigatran etexilate 220 mg group , 874 in the dabigatran etexilate  150 mg group , and 897 in the enoxaparin group were available for the primary efficacy outcome analysis ; the main reasons for exclusion in all three groups were the lack of adequate venographic data . The primary efficacy outcome occurred in 60 ( 6.7 % ) of 897 individuals in the enoxaparin group versus 53 ( 6.0 % ) of 880 patients in the dabigatran etexilate 220 mg group ( absolute difference -0.7 % , 95 % CI -2.9 to 1.6 % ) and 75 ( 8.6 % ) of 874 people in the 150 mg group ( 1.9 % , -0.6 to 4.4 % ) . Both doses were thus non-inferior to enoxaparin . There was no significant difference in major bleeding rates with either dose of dabigatran etexilate compared with enoxaparin ( p=0.44 for 220 mg , p=0.60 for 150 mg ) . The frequency of increases in liver enzyme concentrations and of acute coronary events during the study did not differ significantly between the groups . INTERPRETATION Oral dabigatran etexilate was as effective as enoxaparin in reducing the risk of  venous thromboembolism after total hip replacement surgery , with a similar safety profile BACKGROUND Chronic thromboembolic pulmonary hypertension ( CTPH ) is associated with considerable morbidity and mortality . Its incidence after pulmonary embolism and associated risk factors are not well documented . METHODS We conducted a prospect i ve , long-term , follow-up study to assess the incidence of symptomatic CTPH  in consecutive patients with an acute episode of pulmonary embolism but without prior venous thromboembolism . Patients with unexplained persistent dyspnea during follow-up underwent  transthoracic echocardiography and , if supportive findings were present , ventilation-perfusion lung scanning and pulmonary angiography .  CTPH was considered to be present if systolic and mean pulmonary-artery pressures exceeded 40 mm Hg and 25 mm Hg , respectively ; pulmonary-capillary wedge pressure was normal ; and there was angiographic evidence of disease . RESULTS The cumulative incidence of symptomatic CTPH was 1.0 percent ( 95 percent confidence interval , 0.0 to 2.4 ) at six months , 3.1 percent ( 95 percent confidence interval , 0.7 to 5.5 ) at one year , and 3.8 percent ( 95 percent confidence interval , 1.1 to 6.5 ) at two years . No cases occurred after two years among the patients with more than two years of follow-up data . The following increased the risk of CTPH : a previous pulmonary embolism ( odds ratio , 19.0 ) , younger age ( odds ratio , 1.79 per decade ) , a larger perfusion defect ( odds ratio , 2.22 per decile decrement in perfusion ) , and idiopathic pulmonary embolism at presentation ( odds ratio , 5.70 ) . CONCLUSIONS CTPH is a relatively common , serious complication of pulmonary embolism . Diagnostic and therapeutic strategies for the early identification and prevention of CTPH are needed BACKGROUND Oral anticoagulants , such as dabigatran etexilate , an oral , direct thrombin inhibitor , that do not require monitoring or dose adjustment offer potential for prophylaxis against venous thromboembolism ( VTE ) after total knee replacement surgery . METHODS In this r and omized , double-blind study , 2076 patients undergoing total knee replacement received dabigatran etexilate , 150 mg or 220 mg once-daily , starting with a half-dose 1 - 4 hours after surgery , or subcutaneous enoxaparin 40 mg once-daily , starting the evening before surgery , for 6 - 10 days . Patients were followed-up for 3 months . The primary efficacy outcome was a composite of total VTE ( venographic or symptomatic ) and mortality during treatment , and the primary safety outcome was the incidence of bleeding events . RESULTS The primary efficacy outcome occurred in 37.7 % ( 193 of 512 ) of the enoxaparin group versus 36.4 % ( 183 of 503 ) of the dabigatran etexilate 220 mg group ( absolute difference , -1.3 % ; 95 % CI , -7.3 to 4.6 ) and 40.5 % ( 213 of 526 ) of the 150 mg group ( 2.8 % ; 95 % CI , -3.1 to 8.7 ) . Both doses were noninferior to enoxaparin based on the pre-specified noninferiority criterion . The incidence of major bleeding did not differ significantly between the three groups ( 1.3 % versus 1.5 % and 1.3 % respectively ) . No significant differences in the incidences of liver enzyme elevation and acute coronary events were observed during treatment or follow-up . CONCLUSIONS Dabigatran etexilate ( 220 mg or 150 mg ) was at least as effective and with a similar safety profile as enoxaparin for prevention of VTE after total knee-replacement surgery This trial compared the efficacy and safety of oral dabigatran , a direct thrombin inhibitor , versus subcutaneous enoxaparin for extended thromboprophylaxis in patients undergoing total hip arthroplasty . A total of 2,055 patients were r and omised to 28 - 35 days treatment with oral dabigatran , 220 mg once-daily , starting with a half-dose 1 - 4 hours after surgery , or subcutaneous enoxaparin 40 mg once-daily , starting the evening before surgery . The primary efficacy outcome was a composite of total venous thromboembolism [ VTE ] ( venographic or symptomatic ) and death from all-causes . The main secondary composite outcome was major VTE ( proximal deep-vein thrombosis or non-fatal pulmonary embolism ) plus VTE-related death . The main safety outcome was major bleeding . In total , 2,013 were treated , of whom 1,577 operated patients were included in the primary efficacy analysis . The primary efficacy outcome occurred in 7.7 % of the dabigatran group versus 8.8 % of the enoxaparin group , risk difference ( RD ) -1.1 % ( 95%CI -3.8 to 1.6 % ) ; p<0.0001 for the pre-specified non-inferiority margin . Major VTE plus VTE-related death occurred in 2.2 % of the dabigatran group versus 4.2 % of the enoxaparin group , RD -1.9 % ( -3.6 % to -0.2 % ) ; p=0.03 . Major bleeding occurred in 1.4 % of the dabigatran group and 0.9 % of the enoxaparin group ( p=0.40 ) . The incidence of adverse events , including liver enzyme elevations and cardiac events , during treatment was similar between the groups . Extended prophylaxis with oral dabigatran 220 mg once-daily was as effective as subcutaneous enoxaparin 40 mg once-daily in reducing the risk of VTE after total hip arthroplasty , and superior to enoxaparin for reducing the risk of major VTE . The risk of bleeding and safety profiles were similar BACKGROUND We investigated the efficacy of rivaroxaban , an orally active direct factor Xa inhibitor , in preventing venous thrombosis after total knee arthroplasty . METHODS In this r and omized , double-blind trial , 2531 patients who were to undergo total knee arthroplasty received either oral rivaroxaban , 10 mg once daily , beginning 6 to 8 hours after surgery , or subcutaneous enoxaparin , 40 mg once daily , beginning 12 hours before surgery . The primary efficacy outcome was the composite of any deep-vein thrombosis , nonfatal pulmonary embolism , or death from any cause within 13 to 17 days after surgery . Secondary efficacy outcomes included major venous thromboembolism ( i.e. , proximal deep-vein thrombosis , nonfatal pulmonary embolism , or death related to venous thromboembolism ) and symptomatic venous thromboembolism . The primary safety outcome was major bleeding . RESULTS The primary efficacy outcome occurred in 79 of 824 patients ( 9.6 % ) who received rivaroxaban and in 166 of 878 ( 18.9 % ) who received enoxaparin ( absolute risk reduction , 9.2 % ; 95 % confidence interval [ CI ] , 5.9 to 12.4 ; P<0.001 ) . Major venous thromboembolism occurred in 9 of 908 patients ( 1.0 % ) given rivaroxaban and 24 of 925 ( 2.6 % ) given enoxaparin ( absolute risk reduction , 1.6 % ; 95 % CI , 0.4 to 2.8 ; P=0.01 ) . Symptomatic events occurred less frequently with rivaroxaban than with enoxaparin ( P=0.005 ) . Major bleeding occurred in 0.6 % of patients in the rivaroxaban group and 0.5 % of patients in the enoxaparin group . The incidence of drug-related adverse events , mainly gastrointestinal , was 12.0 % in the rivaroxaban group and 13.0 % in the enoxaparin group . CONCLUSIONS Rivaroxaban was superior to enoxaparin for thromboprophylaxis after total knee arthroplasty , with similar rates of bleeding . ( Clinical Trials.gov number , NCT00361894 . BACKGROUND Low-molecular-weight heparins such as enoxaparin are preferred for prevention of venous thromboembolism after major joint replacement .  Apixaban , an orally active factor Xa inhibitor , might be as effective , have lower bleeding risk , and be easier to use than is enoxaparin . We assessed efficacy and safety 
    Output:
    
Conclusions The economic analyses showed reasonable consistency in the model structures used and the events captured .
The results strongly suggested that NOACs are cost effective alternatives to low molecular-weight heparin .
Dabigatran appeared to be the least cost effective NOAC .