***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: Objective To do an indirect comparison analysis of apixaban against dabigatran etexilate ( 2 doses ) and rivaroxaban ( 1 dose ) , as well as of rivaroxaban against dabigatranetexilate ( 2 doses ) , for their relative efficacy and safety against each other , with particular focus on the secondary prevention population for stroke prevention in atrial fibrillation . A secondary objective was to do the same analysis in the primary prevention cohort . Design Indirect treatment comparisons of phase III clinical trials of stroke prevention in atrial fibrillation , with a focus on the secondary prevention cohorts . A secondary analysis was done on the primary prevention cohort . Data sources Medline and Central ( up to June 2012 ) , clinical trials registers , conference proceedings , and websites of regulatory agencies . Study selection R and omised controlled trials of rivaroxaban , dabigatran , or apixaban compared with warfarin for stroke prevention in atrial fibrillation . Results In the secondary prevention ( previous stroke ) subgroup , when apixaban was compared with dabigatran ( 110 mg and 150 mg twice daily ) for efficacy and safety endpoints , the only significant difference seen was less myocardial infa rct ion ( hazard ratio 0.39 , 95 % confidence interval 0.16 to 0.95 ) with apixaban compared with dabigatran 150 mg twice daily . No significant differences were seen in efficacy and most safety endpoints between apixaban or dabigatran 150 mg twice daily versus rivaroxaban . Less haemorrhagic stroke ( hazard ratio 0.15 , 0.03 to 0.66 ) , vascular death ( 0.64 , 0.42 to 0.99 ) , major bleeding ( 0.68 , 0.47 to 0.99 ) , and intracranial bleeding ( 0.27 , 0.10 to 0.73 ) were seen with dabigatran 110 mg twice daily versus rivaroxaban . In the primary prevention ( no previous stroke ) subgroup , apixaban was superior to dabigatran 110 mg twice daily for disabling or fatal stroke ( hazard ratio 0.59 , 0.36 to 0.97 ) . Compared with dabigatran 150 mg twice daily , apixaban was associated with more stroke ( hazard ratio 1.45 , 1.01 to 2.08 ) and with less major bleeding ( 0.75 , 0.60 to 0.94 ) , gastrointestinal bleeding ( 0.61 , 0.42 to 0.89 ) , and other location bleeding ( 0.74 , 0.58 to 0.94 ) . Compared with rivaroxaban , dabigatran 110 mg twice daily was associated with more myocardial infa rct ion events . No significant differences were seen for the main efficacy and safety endpoints between dabigatran 150 mg twice daily and rivaroxaban , or in efficacy endpoints between apixaban and rivaroxaban . Apixaban was associated with less major bleeding ( hazard ratio 0.61 , 0.48 to 0.78 ) than rivaroxaban . Conclusions For secondary prevention , apixaban , rivaroxaban , and dabigatran had broadly similar efficacy for the main endpoints , although the endpoints of haemorrhagic stroke , vascular death , major bleeding , and intracranial bleeding were less common with dabigatran 110 mg twice daily than with rivaroxaban . For primary prevention , the three drugs showed some differences in relation to efficacy and bleeding . These results are hypothesis generating and should be confirmed in a head to head r and omised trial OBJECTIVES To investigate the effects of pre-conception thromboprophylaxis among patients with recurrent spontaneous abortion and antiphospholipid syndrome . METHODS A r and omized placebo-controlled trial enrolled patients with a history of recurrent spontaneous abortions and antiphospholipid syndrome who attended an Egyptian center between January 2011 and June 2013 . Using a computer-generated sequence , patients were r and omly allocated to receive 41 mg enoxaparin subcutaneously plus 81 mg aspirin daily pre-conception , or to receive placebo pre-conception . All patients received enoxaparin and aspirin following identification of fetal heart pulsation . The primary outcomes were live-birth rate and clinical -pregnancy rate at 0 - 6 months , and at 6 - 12 months . Intention-to-treat analyses were performed . Clinicians , investigators , and data analysts were masked to the treatment assignments . RESULTS The study enrolled 180 patients ( 90 in each group ) . No significant difference was observed between the intervention and control groups in the live-birth rate ( 67[74 % ] vs 59[66 % ] ; P=0.25 ) . At 0 - 6 months , the clinical -pregnancy rate was higher in the intervention group ( 50[56%]vs 30[33 % ] , P=0.02 ) . No significant difference between the intervention and control groups was observed in the clinical -pregnancy rate at 6 - 12 months ( 32[36 % ] vs 35[39 % ] , P=0.52 ) . CONCLUSION Among patients with recurrent spontaneous abortion and antiphospholipid syndrome  , pre-conception enoxaparin increased the clinical -pregnancy rate at 0 - 6 months , but did not affect the clinical -pregnancy rate at 6 - 12 months or the live-birth rate . Clinical Trials.gov : NCT01661439 OBJECTIVE We attempted to compare the use of low-dose heparin with a st and ard dose of 40 mg prednisone daily ( both plus low-dose aspirin ) for treatment of pregnant women with antiphospholipid antibody-associated recurrent fetal loss with respect to maternal and perinatal morbidity and efficacy in prevention of fetal death . STUDY DESIGN A multicenter r and omized trial included 20 patients . Generalizability of results from r and omized patients was evaluated by means of additional data from 13 women refusing and 12 women ineligible for r and omization . Data from study groups were compared with Fisher 's exact test , and generalizability was evaluated with a chi 2 test for trend . RESULTS Live birth rates were the same ( 75 % ) with either treatment , but " serious " maternal morbidity and the frequency of preterm delivery were significantly higher among women r and omly assigned to prednisone ( p = 0.02 vs p = 0.006 ) . Preterm delivery among prednisone-treated women was usually associated with premature rupture of the membranes or preeclampsia . These results could be generalized to the other groups of women ascertained during the course of the study . CONCLUSIONS Low-dose heparin should be preferred to prednisone when treatment is indicated for high-risk pregnant women with antiphospholipid antibodies Summary Background Rivaroxaban is established for the treatment and secondary prevention of venous thromboembolism , but whether it is useful in patients with antiphospholipid syndrome is uncertain . Methods This r and omised , controlled , open-label , phase 2/3 , non-inferiority trial , done in two UK hospitals , included patients with antiphospholipid syndrome who were taking warfarin for previous venous thromboembolism , with a target international normalised ratio of 2·5 . Patients were r and omly assigned 1:1 to continue with warfarin or receive 20 mg oral rivaroxaban daily . R and omisation was done central ly , stratified by centre and patient type ( with vs without systemic lupus erythematosus ) . The primary outcome was percentage change in endogenous thrombin potential ( ETP ) from r and omisation to day 42 , with non-inferiority set at less than 20 % difference from warfarin in mean percentage change . Analysis was by modified intention to treat . Other thrombin generation parameters , thrombosis , and bleeding were also assessed . Treatment effect was measured as the ratio of rivaroxaban to warfarin for thrombin generation . This trial is registered with the IS RCT N registry , number IS RCT N68222801 . Findings Of 116 patients r and omised between June 5 , 2013 , and Nov 11 , 2014 , 54 who  received rivaroxaban  and 56 who received warfarin were assessed . At day 42 , ETP was higher in the rivaroxaban than in the warfarin group ( geometric mean 1086 nmol/L per min , 95 % CI 957–1233 vs 548 , 484–621 , treatment effect 2·0 , 95 % CI 1·7–2·4 , p<0·0001 ) . Peak thrombin generation was lower in the rivaroxaban group ( 56 nmol/L , 95 % CI 47–66 vs 86 nmol/L , 72–102 , treatment effect 0·6 , 95 % CI 0·5–0·8 , p=0·0006 ) . No thrombosis or major bleeding were seen . Serious adverse events occurred in four patients in each group . Interpretation ETP for rivaroxaban did not reach the non-inferiority threshold , but as there was no increase in thrombotic risk compared with st and ard-intensity warfarin , this drug could be an effective and safe alternative in patients with antiphospholipid syndrome and previous venous thromboembolism . Funding Arthritis Research UK , Comprehensive Clinical Trials Unit at UCL , LUPUS UK , Bayer , National Institute for Health Research Biomedical Research Centre Background : Antiphospholipid syndrome ( APS ) is an acquired thrombophilia characterized by thrombosis , pregnancy morbidity , and the presence of characteristic antibodies . Current therapy for patients having APS with a history of thrombosis necessitates anticoagulation with the vitamin K antagonist warfarin , a challenging drug to manage . Apixaban , approved for the treatment and prevention of venous thrombosis with a low rate of bleeding observed , has never been studied among patients with APS . Aims and Methods : We report study rationale and design of Apixaban for the Secondary Prevention of Thrombosis Among Patients With Antiphospholipid Syndrome ( ASTRO-APS ) , a prospect i ve r and omized open-label blinded event pilot study that will r and omize patients with a clinical diagnosis of APS receiving therapeutic anticoagulation to either adjusted-dose warfarin or apixaban  2.5 mg twice a day . We aim to report our ability to identify , recruit , r and omize , and retain patients with APS r and omized to apixaban compared with warfarin . We will report clinical ly important outcomes of thrombosis and bleeding . All clinical outcomes will be adjudicated by a panel blinded to the treatment arm . A unique aspect of this study is the enrollment of patients with an established clinical diagnosis of APS . Also unique is our use of electronic medical record interrogation techniques to identify patients who would likely meet our inclusion criteria and use of an electronic portal for follow-up visit data capture . Conclusion : ASTRO-APS will be the largest prospect i ve study to date comparing a direct oral anticoagulant with warfarin among patients with APS for the secondary prevention of thrombosis . Our inclusion criteria assure that outcomes obtained will be clinical ly applicable to the routine management of patients with APS receiving indefinite anticoagulation OBJECTIVE To determine whether low molecular weight heparin ( LMWH ) plus low-dose aspirin ( LDA ) is comparable in efficacy and safety to unfractionated heparin ( UFH ) plus LDA in the management of pregnant women with a history of recurrent spontaneous abortion secondary to antiphospholipid syndrome ( APS ) . METHODS In a r and omized prospect i ve study , 60 women with a history of 3 or more consecutive spontaneous abortions and positive antiphospholipid antibodies were assigned in equal numbers to receive either UFH ( 5000 units , twice daily ) plus LDA , or LMWH ( enoxaparin 40 mg , once daily ) plus LDA as soon as pregnancy was diagnosed . RESULTS Twenty-four women in the LMWH group ( 80 % ) and 20 women in the UFH group ( 66.67 % ) delivered a viable infant ( P = 0.243 ) . There were no significant differences in pregnancy complications or neonatal morbidity between the 2 groups . There were no incidences of excessive bleeding , thrombocytopenia , or osteoporotic fractures in either group . CONCLUSION LMWH plus LDA was successfully used as an alternative to UFH plus LDA in the management of recurrent abortion secondary to APS . The results highlight the need for a larger r and omized controlled trial to determine whether LMWH plus LDA should be the treatment of choice for recurrent abortion secondary to APS . Clinical trials.gov NCT01051778 OBJECTIVE The purpose of this study was to compare the use of low-dose aspirin alone with heparin and low-dose aspirin in the treatment of the antiphospholipid antibody syndrome . STUDY DESIGN A prospect i ve , single-center trial included 50 patients who were alternately assigned to treatment . Each patient had at least three consecutive spontaneous pregnancy losses , positive antiphospholipid antibodies on two occasions , and a complete evaluation . Data were 
    Output:
    
There is insufficient evidence to demonstrate benefit or harm of using anticoagulants with or without ASA versus ASA alone in people with aPL antibodies and a history of recurrent pregnancy loss and with no such history ; ASA versus placebo in people with aPL antibodies ; and ASA with LMWH versus placebo or IVIG , and ASA with high-dose LMWH versus ASA with low-dose LMWH or UFH , in women with aPL antibodies and a history of recurrent pregnancy loss , for the primary prevention of thrombotic events .
In a mixed population of people with a history of previous pregnancy loss and without such a history treated with anticoagulant combined with ASA , the incidence of minor bleeding ( nasal bleeding , menorrhagia ) was increased when compared with ASA alone .