***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: CONTEXT Despite many therapeutic advances , mortality in patients with acute ST-segment elevation myocardial infa rct ion ( STEMI ) remains high . The role of additional antithrombotic agents is unclear , especially among patients not receiving reperfusion therapy . OBJECTIVE To evaluate the effect of fondaparinux , a factor Xa inhibitor , when initiated early and given for up to 8 days vs usual care ( placebo in those in whom unfractionated heparin [ UFH ] is not indicated [ stratum 1 ] or unfractionated heparin for up to 48 hours followed by placebo for up to 8 days [ stratum 2 ] ) in patients with STEMI . DESIGN , SETTING , AND PARTICIPANTS R and omized double-blind comparison of fondaparinux 2.5 mg once daily or control for up to 8 days in 12,092 patients with STEMI from 447 hospitals in 41 countries ( September 2003-January 2006 ) . From day 3 through day 9 , all patients received either fondaparinux or placebo according to the original r and omized assignment . MAIN OUTCOME MEASURES Composite of death or reinfa rct ion at 30 days ( primary ) with secondary assessment s at 9 days and at final follow-up ( 3 or 6 months ) . RESULTS Death or reinfa rct ion at 30 days was significantly reduced from 677 ( 11.2 % ) of 6056 patients in the control group to 585 ( 9.7 % ) of 6036 patients in the fondaparinux group ( hazard ratio [ HR ] , 0.86 ; 95 % confidence interval [ CI ] , 0.77 - 0.96 ; P = .008 ) ; absolute risk reduction , 1.5 % ; 95 % CI , 0.4%-2.6 % ) . These benefits were observed at 9 days ( 537 [ 8.9 % ] placebo vs 444 [ 7.4 % ] fondaparinux ; HR , 0.83 ; 95 % CI , 0.73 - 0.94 ; P = .003 , and at study end ( 857 [ 14.8 % ] placebo vs 756 [ 13.4 % ] fondaparinux ; HR , 0.88 ; 95 % CI , 0.79 - 0.97 ; P = .008 ) . Mortality was significantly reduced throughout the study . There was no heterogeneity of the effects of fondaparinux in the 2 strata by planned heparin use . However , there was no benefit in those undergoing primary percutaneous coronary intervention . In other patients in stratum 2 , fondaparinux was superior to unfractionated heparin in preventing death or reinfa rct ion at 30 days ( HR , 0.82 ; 95 % CI , 0.66 - 1.02 ; P = .08 ) and at study end ( HR , 0.77 ; 95 % CI , 0.64 - 0.93 ; P = .008 ) . Significant benefits were observed in those receiving thrombolytic therapy ( HR , 0.79 ; P = .003 ) and those not receiving any reperfusion therapy ( HR , 0.80 ; P = .03 ) . There was a tendency to fewer severe bleeds ( 79 for placebo vs 61 for fondaparinux ; P = .13 ) , with significantly fewer cardiac tamponade ( 48 vs 28 ; P = .02 ) with fondaparinux at 9 days . CONCLUSION In patients with STEMI , particularly those not undergoing primary percutaneous coronary intervention , fondaparinux significantly reduces mortality and reinfa rct ion without increasing bleeding and strokes . TRIAL REGISTRATION Clinical Trials.gov Identifier NCT00064428 Background — The optimal anticoagulant regimen for percutaneous coronary intervention ( PCI ) remains to be determined . Otamixaban , a selective and direct inhibitor of factor Xa , was investigated in patients undergoing nonurgent percutaneous coronary intervention . Methods and Results — In this double-blind , double-dummy , parallel-group , dose-ranging trial , 947 patients were r and omly assigned to either 1 of 5 weight-adjusted otamixaban regimens or weight-adjusted unfractionated heparin ( UFH ) before percutaneous coronary intervention . The primary end points were change in prothrombin fragments 1 + 2 ( F1 + 2 ) , and anti-factor Xa activity . The main secondary end points were Thrombolysis In Myocardial Infa rct ion ( TIMI ) bleeding at day 3 or hospital discharge ( whichever came first ) and 30-day ischemic events . The median change in F1 + 2 from baseline to the end of infusion was greater with the highest otamixaban dose compared with UFH ( −0.3 versus −0.2 ng/mL , P=0.008 ) . Anti-factor Xa levels were 65 , 155 , 393 , 571 , and 691 ng/mL with otamixaban doses 1 to 5 , respectively . Significant TIMI bleeding ( major or minor ) occurred in 2.0 % , 1.9 % , 3.8 % , 3.9 % , and 2.6 % of patients receiving otamixaban doses 1 to 5 , respectively , and in 3.8 % of patients receiving UFH .  Four TIMI major bleeds were observed . Ischemic events occurred in 5.8 % , 7.1 % , 3.8 % , 2.5 % , and 5.1 % of patients receiving otamixaban doses 1 to 5 , respectively , and in 5.6 % of patients receiving UFH . Conclusions — Otamixaban  reduced F1 + 2 significantly more than UFH at the highest dose regimen , whereas no significant difference in the incidence of TIMI bleeding was observed between the otamixaban and UFH groups . These results set the stage for adequately powered clinical outcome trials of selective direct factor Xa inhibition in patients with acute coronary syndromes Background —Factor Xa plays a central role in the generation of thrombin , making it a novel target for treatment of arterial thrombosis . Fondaparinux is a synthetic factor Xa inhibitor that has been shown to be superior to st and ard therapies for the prevention of venous thrombosis . We performed a r and omized trial to determine the safety and feasibility of fondaparinux in the percutaneous coronary intervention ( PCI ) setting . Methods and Results —A total of 350 patients undergoing elective or urgent PCI were r and omized in a blinded manner to receive unfractionated heparin ( UFH ) , 2.5 mg fondaparinux IV , or 5.0 mg fondaparinux IV . R and omization was stratified for planned or no planned use of glycoprotein ( GP ) IIb/IIIa antagonists . The primary safety outcome was total bleeding , which was a combination of major and minor bleeding events . The incidence of total bleeding was 7.7 % in the UFH group and 6.4 % in the combined fondaparinux groups ( hazard ratio , 0.81 ; 95 % confidence interval , 0.35 to 1.84 ; P=0.61 ) . Bleeding was less common in the 2.5-mg fondaparinux group compared with the 5-mg fondaparinux group ( 3.4 % versus 9.6 % , P=0.06 ) . The composite efficacy outcome of all-cause mortality , myocardial infa rct ion , urgent revascularization , or need for a bailout GPIIb/IIIa antagonist was 6.0 % in the UFH group and 6.0 % in the fondaparinux group , with no significant difference in efficacy among the fondaparinux doses compared with UFH . Coagulation marker analysis at 6 and 12 hours after PCI demonstrated that fondaparinux was superior to UFH in inducing a sustained reduction in markers of thrombin generation , as measured by prothrombin fragment F1.2 ( P=0.02 ) . Conclusions —In this pilot study of patients undergoing contemporary PCI , factor Xa inhibition with the synthetic anticoagulant fondaparinux in doses of 2.5 and 5.0 mg was comparable to UFH for clinical safety and efficacy outcomes . These data form the basis for further evaluation of fondaparinux in arterial thrombosis BACKGROUND The combined use of anticoagulants , antiplatelet agents , and invasive coronary procedures reduces ischemic coronary events but also increases bleeding in patients with acute coronary syndromes . We therefore assessed whether fondaparinux would preserve the anti-ischemic benefits of enoxaparin while reducing bleeding . METHODS We r and omly assigned 20,078 patients with acute coronary syndromes to receive either fondaparinux ( 2.5 mg daily ) or enoxaparin ( 1 mg per kilogram of body weight twice daily ) for a mean of six days and evaluated death , myocardial infa rct ion , or refractory ischemia at nine days ( the primary outcome ) ; major bleeding ; and their combination . Patients were followed for up to six months . RESULTS The number of patients with primary - outcome events was similar in the two groups ( 579 with fondaparinux [ 5.8 percent ] vs. 573 with enoxaparin [ 5.7 percent ] ; hazard ratio in the fondaparinux group , 1.01 ; 95 percent confidence interval , 0.90 to 1.13 ) , satisfying the noninferiority criteria . The number of events meeting this combined outcome showed a nonsignificant trend toward a lower value in the fondaparinux group at 30 days ( 805 vs. 864 , P=0.13 ) and at the end of the study ( 1222 vs. 1308 , P=0.06 ) . The rate of major bleeding at nine days was markedly lower with fondaparinux than with enoxaparin ( 217 events [ 2.2 percent ] vs. 412 events [ 4.1 percent ] ; hazard ratio , 0.52 ; P<0.001 ) . The composite of the primary outcome and major bleeding at nine days favored fondaparinux ( 737 events [ 7.3 percent ] vs. 905 events [ 9.0 percent ] ; hazard ratio , 0.81 ; P<0.001 ) . Fondaparinux was associated with a significantly reduced number of deaths at 30 days ( 295 vs. 352 , P=0.02 ) and at 180 days ( 574 vs. 638 , P=0.05 ) . CONCLUSIONS Fondaparinux is similar to enoxaparin in reducing the risk of ischemic events at nine days , but it substantially reduces major bleeding and improves long term mortality and morbidity . ( Clinical Trials.gov number , NCT00139815 . ) AIM OF THE STUDY To assess the antithrombotic properties of SR90107/ORG31540 . a sulfated pentasaccharide , which enhances specifically antithrombin III mediated inactivation of factor-Xa , in a clinical setting known to promote arterial thrombosis , i.e. coronary angioplasty . METHODS AND RESULTS Percutaneous transluminal coronary angioplasty ( PTCA ) was carried out with conventional balloons with a single 5 min intravenous infusion of 12 mg pentasaccharide , and 500 mg intravenous aspirin . Heparin was not allowed before , during PTCA , and within 24 h after PTCA . The primary end point was the rate of abrupt vessel closure during and within 24 h after the procedure . The sample size was set at 60 evaluable patients , in order to be able to conclude with a good level of confidence ( > 95 % ) that the abrupt vessel closure rate was less than 10 % , if less than 3 abrupt vessel closures were observed . Seventy-one patients were included in the study , of whom 10 needed elective stenting  , and were not considered as evaluable for efficacy . Two out of the 61 remaining evaluable patients experienced acute vessel closure during the study period [ 3.28 % , 95 % confidence interval ( 0.4 % ; 11.4 % ) ] . No major bleeding occurred . The drug plasma concentrations reached 1.91+/-0.39 mg/ ] , 10 min after pentasaccharide injection , and decreased on average to 1 . 18+/-0.27 mg/l at 2 h , and to 0.36+/-0.11 mg/l at 23 h after administration of pentasaccharide .  Activated clotting time ( ACT ) and activated partial thromboplastin ( aPTT ) time remained within normal range . Thrombin-antithrombin complex levels fell from 22+/-17.1 to 4.5+/-3.4 microg/ml , prothrombin fragment 1 + 2 levels decreased from 2.15+/-1.01 to 1.73+/-0.87 , and activated factor VII levels decreased from 43.4+/-16.8 mU/ml to 18.9+/-7.3 mU/ml respectively from baseline to 2 h following injection of the tested drug . CONCLUSIONS Administration of pentasaccharide led to the inhibition of thrombin generation without modification of aPTT and ACT . The rate of abrupt vessel closure was within range of rates reported in 
    Output:
    
The therapeutic efficacy of factor Xa inhibitors in ACS seemed to be related to a reduced risk in all-cause mortality at 90 to 180 days , with a better safety profile than enoxaparin in terms of reduce incidence of major and minor bleeding