***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: We compared the efficacy and safety of low-molecular-weight heparin with that of low-dose unfractionated heparin in the prevention of  venous thromboembolism after total knee arthroplasty in a prospect i ve , r and omized , multicenter trial . One hundred and eighty-five patients were r and omly assigned to two groups : ninety-two received low-molecular-weight heparin ( forty milligrams of enoxaparin the evening before the operation and once a day subsequently ) and ninety-three received unfractionated heparin ( 5000 international units the evening before the operation and three times a day thereafter ) . The prophylaxis was continued until bilateral ascending venography was performed six to nine days after the operation or , if venography was not done , until the eighth postoperative day . Venography revealed a prevalence of deep-vein thrombosis of 27 per cent ( twenty-five of ninety-three patients ) in the group that received unfractionated heparin and 23 per cent ( twenty-one of ninety-two patients ) in the group that received low-molecular-weight heparin . The difference was not significant ( p = 0.6 ) . Five patients ( 5 per cent ) who received unfractionated heparin and 3 patients ( 3 per cent ) who received low-molecular-weight heparin had a deep-vein thrombosis in the proximal veins . Two patients who received unfractionated heparin and one who received low-molecular-weight heparin had clinical symptoms suggestive of a pulmonary embolism . None of these three patients had a positive ventilation-perfusion scan . There were no deaths , major bleeding episodes , or wound hematomas necessitating operative intervention or discontinuation of the anticoagulation in the series . ( ABSTRACT TRUNCATED AT 250 WORDS BACKGROUND Heparins and warfarin are currently used as venous thromboembolism ( VTE ) prophylaxis in surgery . Inhibition of factor ( F ) Xa provides a specific mechanism of anticoagulation and the potential for an improved benefit-risk profile . OBJECTIVES To evaluate the safety and efficacy of apixaban , a potent , direct , oral inhibitor of FXa , in patients following total knee replacement ( TKR ) , and to investigate dose-response relationships . PATIENTS / METHODS A total of 1238 patients were r and omized to one of six double-blind apixaban doses [ 5 , 10 or 20 mg day(-1 ) administered as a single ( q.d . ) or a twice-daily divided dose ( b.i.d . ) ] , enoxaparin ( 30 mg b.i.d . ) or open-label warfarin ( titrated to an International Normalized Ratio of 1.8 - 3.0 ) . Treatment lasted 10 - 14 days , commencing 12 - 24 h after surgery with apixaban or enoxaparin , and on the evening of surgery with warfarin . The primary efficacy outcome was a composite of VTE ( m and atory venography ) and all-cause mortality during treatment . The primary safety outcome was major bleeding . RESULTS A total of 1217 patients were eligible for safety and 856 patients for efficacy analysis . All apixaban groups had lower primary efficacy event rates than either comparator . The primary outcome rate decreased with increasing apixaban dose ( P = 0.09 with q.d./b.i.d . regimens combined , P = 0.19 for q.d . and P = 0.13 for b.i.d . dosing).A significant dose-related increase in the incidence of total adjudicated bleeding events was noted in the q.d . ( P = 0.01 ) and b.i.d . ( P = 0.02 ) apixaban groups ; there was no difference between q.d . and b.i.d . regimens . CONCLUSIONS Apixaban in doses of 2.5 mg b.i.d . or 5 mg q.d . has a promising benefit-risk profile compared with the current st and ards of care following TKR Introduction : We compared the efficacy and safety of st and ard heparin to that of low molecular weight heparin ( Enoxaparin ) in 100 hip replacement patients . Material s and methods : A total of 100 patients who underwent total hip replacement surgery were r and omised to receive a study medication . Enoxaparin was administered to 50 patients ( prophylaxis with subcutaneous injection of 40 mg of Enoxaparin daily was initiated 12 h preoperatively ) , and heparin ( subcutaneous st and ard heparin initiated 8 h preoperatively on a dose of 5,000 IU and continued to 15,000 IU per day in three equal dosages every 8 h ) was given to 50 patients . Each treatment was continued until the patients were discharged from the hospital . They were made to undergo lower extremity duplex ultrasonography for deep vein thrombosis before discharge and discontinued from medication if no pathology was found . The primary parameter to determine the efficacy was the prevalence of venous thromboembolic disease . The primary parameter to determine safety was the prevalence of major bleeding . Results : Two patients in the heparin group developed DVT , which was detected by routine duplex ultrasonography at the end of hospitalisation , and two patients in the exoparine group were detected with late DVT during the postoperative period of 6 weeks . Seven patients had minor and major bleeding in both the groups . Six patients in the heparin group discontinued from medication because of hepatic , renal dysfunctions , and serious discharges from the wound . Conclusion : Enoxaparin is as safe and as effective as st and ard heparin in total hip replacement surgery Background — Rivaroxaban ( BAY 59 - 7939)—an oral , direct Factor Xa inhibitor — could be an alternative to heparins and warfarin for the prevention and treatment of thromboembolic disorders . Methods and Results — This r and omized , double-blind , double-dummy , active-comparator – controlled , multinational , dose-ranging study assessed the efficacy and safety of once-daily rivaroxaban relative to enoxaparin for prevention of venous thromboembolism in patients undergoing elective total hip replacement . Patients ( n=873 ) were r and omized to once-daily oral rivaroxaban doses of 5 , 10 , 20 , 30 , or 40 mg ( initiated 6 to 8 hours after surgery ) or a once-daily subcutaneous enoxaparin dose of 40 mg ( given the evening before and ≥6 hours after surgery ) . Study drugs were continued for an additional 5 to 9 days ; m and atory bilateral venography was performed the following day . The primary end point ( composite of any deep vein thrombosis , objective ly confirmed pulmonary embolism , and all-cause mortality ) was observed in 14.9 % , 10.6 % , 8.5 % , 13.5 % , 6.4 % , and 25.2 % of patients receiving 5 , 10 , 20 , 30 , and 40 mg rivaroxaban , and 40 mg enoxaparin , respectively ( n=618 , per- protocol population ) . No significant dose – response relationship was found for efficacy ( P=0.0852 ) . Major postoperative bleeding was observed in 2.3 % , 0.7 % , 4.3 % , 4.9 % , 5.1 % , and 1.9 % of patients receiving 5 , 10 , 20 , 30 , and 40 mg rivaroxaban , and 40 mg enoxaparin , respectively ( n=845 , safety population ) , representing a significant dose – response relationship ( P=0.0391 ) . Conclusions — Rivaroxaban showed efficacy and safety similar to enoxaparin for thromboprophylaxis after total hip replacement , with the convenience of once-daily oral dosing and without the need for coagulation monitoring . When both efficacy and safety are considered , these results suggest that 10 mg rivaroxaban once daily should be investigated in phase III studies A r and omized , parallel-group , open-label clinical trial ( the physicians , patients , and staff were not blinded with regard to the regimen that had been used ) was conducted , between December 1988 and September 1990 , to compare the safety and efficacy of enoxaparin , a low-molecular-weight heparin , with the safety and efficacy of unfractionated heparin for the prevention of deep venous thrombosis after elective hip replacement . Six hundred and ten patients were r and omized , and 607 patients received one of the study medications . The evaluations of efficacy included contrast-media venography , non-invasive vascular examination , and clinical examination . Data on efficacy were available for 604 patients , who had been assigned to one of three treatment groups : thirty milligrams of enoxaparin every twelve hours ( 194 patients ) , forty milligrams of enoxaparin once daily ( 203 patients ) , or 5000 units of unfractionated heparin every eight hours ( 207 patients ) . All drugs were administered subcutaneously . Dosages were not adjusted on the basis of the results of coagulation tests or the body weight of the patient . Treatment was initiated within twenty-four hours after the operation and continued for a maximum of seven days . The primary safety outcome was the occurrence of bleeding episodes . An intent-to-treat patient analysis revealed that deep venous thrombosis occurred in nine ( 5 per cent ) of the 194 patients who received thirty milligrams of enoxaparin every twelve hours , thirty ( 15 per cent ) of the 203 patients who received forty milligrams of enoxaparin once daily , and twenty-four ( 12 per cent ) of the 207 patients who received unfractionated heparin . The rate of deep venous thrombosis was significantly lower in the group that received thirty milligrams of enoxaparin every twelve hours than in the group that received unfractionated heparin ( p = 0.03 ) and in the group that received forty milligrams of enoxaparin once daily ( p = 0.0002 ) . No clinical ly symptomatic pulmonary embolism was observed during the treatment or follow-up phase of this study in the group that received thirty milligrams of enoxaparin every twelve hours . Analysis of evaluable patients revealed a marked reduction in the rate of deep venous thrombosis in the group that received thirty milligrams of enoxaparin every twelve hours ( eight [ 6 per cent ] of 136 patients ) compared with the group that received heparin ( twenty-one [ 15 per cent ] of 145 patients ) ( p = 0.10 ) ; however , this difference was not significant because of the small number of patients included in this analysis . ( ABSTRACT TRUNCATED AT 400 WORDS A series of 80 patients operated for total hip prosthesis under epidural anesthesia was r and omly allocated to treatment with Kabi 2165 ( n = 40 ) : 2,500 U anti-Xa preoperatively and evening of operation and 2,500 U anti-Xa morning and evening daily up to the 9th or 10th day postoperatively , or st and ard heparin ( n = 40 ) : 3,750 U preoperatively and then 8 hourly , at a dose adjusted with thrombin time and cephalin + activator time , daily up to the 9th or 10th day .  Phlebography  was performed routinely on the 9th or 10th day . Venous thrombosis occurred in 7 patients ( 17.5 % ) in the Kabi 2165 group , including two high , potentially emboligenic , localizations ( 5 % ) , and in 4 patients ( 10 % ) in the st and ard heparin group , including 2 potentially emboligenic clots ( 5 % ) . The difference is not statistically significant ( total number : p = 0.5 ; potentially emboligenic : p = 0.33 ) . Pulmonary embolism did not occur . Overall tolerance , evaluated from hemoglobin and hematocrit values , intra- and post-operative bleeding and operation wound hematoma and at injection site was comparable in the two groups 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 etexil 
    Output:
    
Compared with patients who received unfractionated heparin ( UFH ) , patients who received LMWHs had fewer pulmonary embolism , total deep vein thrombosis ( DVT ) , major bleeding , and heparin-induced thrombocytopenia events .
Compared with patients who received vitamin K antagonists ( VKAs ) , patients who received LMWHs had fewer total DVT and distal DVT events but reported increased major bleeding , minor bleeding , and surgical site bleeding events .
Major efficacy end points such as symptomatic venous thromboembolism , pulmonary embolism , and nonfatal pulmonary embolism showed similar benefits of therapy with LMWHs and VKAs .
Compared with patients receiving factor Xa inhibitors , patients who received LMWHs had more major venous thromboembolism , pulmonary embolism , total DVT , asymptomatic DVT , proximal DVT , and distal DVT events but fewer major bleeding events .
Compared with patients receiving direct thrombin inhibitors ( DTIs ) , patients who received LMWHs had more major venous thromboembolism , total DVT , and proximal DVT events without significantly negatively affecting bleeding .
However , patients who received LMWHs had fewer distal DVT events versus those who received DTIs .
Subgroup analyses indicated differences based on the surgical procedure and individual drug within certain pharmacologic classes .
According to moderate-to-high strength of evidence , LMWH prophylaxis provides additional benefits with less harm compared with UFH .
With predominantly moderate strength of evidence , the balance of benefits to harms for factor Xa inhibitors or DTIs compared with LMWHs seems favorable .
With predominantly low-to-moderate strength of evidence , the known benefits in total DVT and distal DVT with LMWHs versus VKAs may not be sufficient to counteract the increased risk of bleeding