***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 treatment of unstable angina targets the specific pathophysiological thrombotic process at the site of the active culprit lesion . In unstable angina due to a restenotic lesion , smooth muscle cell proliferation and increased vasoreactivity may play a more important role than thrombus formation . Therefore , the relative benefits of nitroglycerin and heparin might differ in unstable angina associated with restenosis compared with classic unstable angina . METHODS AND RESULTS We r and omized 200 patients hospitalized for unstable angina within 6 months after angioplasty ( excluding those with intracoronary stents ) to double-blind administration of intravenous nitroglycerin , heparin , their combination , or placebo  for 63+/-30 hours . Recurrent angina occurred in 75 % of patients in the placebo and heparin-alone groups , compared with 42.6 % of patients in the nitroglycerin-alone group and 41.7 % of patients in the nitroglycerin-plus-heparin group ( P<0.003 ) . Refractory angina requiring angiography occurred in 22.9 % , 29.2 % , 4 . 3 % , and 4.2 % of patients , respectively ( P<0.002 ) . The odds ratios for being event free were 0.24 ( 95 % CI , -0.13 to 0.45 , P=0.0001 ) for nitroglycerin versus no nitroglycerin and 0.98 ( 95 % CI , -0.55 to 1 . 73 , P = NS ) for heparin versus no heparin . No patient died or suffered myocardial infa rct ion . CONCLUSIONS Intravenous nitroglycerin is highly effective in preventing adverse ischemic events ( recurrent or refractory angina ) in patients with unstable angina secondary to restenosis , whereas heparin has no effect 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 Antiplatelet therapy with aspirin and antithrombotic therapy with heparin both prevent the complications of unstable angina ; however , no definitive data exist on the relative clinical efficacy of the two drugs . Methods and Results Aspirin ( 325 mg bid ) or heparin ( 5000-U intravenous bolus followed by a perfusion titrated to the APTT ) were compared in a double-blind r and omized trial of 484 patients in two cohorts enrolled sequentially . The study was initiated at admission to hospital at a mean of 8.3±7.8 hours after the last episode of pain . End points were assessed 5.7±3.3 days later , when the decision for long-term management was made . Myocardial infa rct ion occurred in 2 ( 0.8 % ) of the 240 patients r and omized to heparin  and in 9 ( 3.7 % ) of the 244 r and omized to aspirin ( P=.035 ) , an odds ratio of 0.22 and a risk difference of 2.9%o ( 95 % confidence limits , 0.3 % to 5.6 % ) with heparin . The only death result ed from a myocardial infa rct ion in an aspirin patient . Survival curves with Cox logistic regression analysis showed that the improvement in survival without myocardial infa rct ion  with heparin ( P=.035 ) was independent of other baseline characteristics . Conclusions This study documents that heparin prevents myocardial infa rct ion better than aspirin during the acute phase of unstable angina Platelet glycoprotein IIb/IIIa inhibitors have been extensively studied in the treatment of patients with ischemic heart disease . Data regarding the use of these agents in the absence of concomitant intravenous heparin have been conflicting . We sought to determine , using propensity analysis , whether the benefit of eptifibatide , a IIb/IIIa inhibitor , in the treatment of acute coronary syndromes is affected by the concurrent administration of heparin . By trial design , patients were r and omized to either eptifibatide or placebo , whereas use of intravenous heparin was left to the discretion of treating physicians . The effect of eptifibatide on the 30-day composite end point of death or myocardial infa rct ion was studied in patients who received heparin  and those who did not . Propensity analysis methods were used to control for confounding and presumed selection biases . Among 5,576 patients who were receiving heparin when the bolus dose of the study drug was administered , eptifibatide was associated with a reduced composite end point rate ( 13 % ) compared with that of placebo ( 14.5 % vs 16.6 % , p = 0.03 ) . In contrast , among 1,441 patients who were not receiving heparin , there was no difference in 30-day event rates with eptifibatide compared with placebo ( 13.7 % vs 13.1 % , p > 0.7 ) . After a propensity score for use of heparin was developed , however , use of heparin did not affect the reduced risk associated with eptifibatide ( adjusted relative risk [ RR ] for heparin-eptifibatide interaction term 0.90 , 95 % confidence interval [ CI ] 0.61 to 1.32 , p > 0.5 ) , but the propensity for heparin use was a strong predictor of events ( adjusted RR 1.76 , 95 % CI 1.42 to 2.17 , p < 0.001 ) . The use of eptifibatide independently predicted a lower risk of events ( adjusted RR 0.31 , 95 % CI 0.10 to 0.93 , p = 0.04 ) . Thus , the apparent positive impact of heparin on the benefits of eptifibatide therapy was largely due to confounding and bias Heparin , aspirin with dipyridamole or placebo were given to 266 patients with pre-infa rct ion angina treated with isosorbide dinitrate , beta blockers and nifedipidine .  The number of patients who developed acute myocardial infa rct ion ( MI ) in the next 72 hours was comparable in all 3 groups . However , patients on heparin  developed only 3.2 % ( 2 out of 61 ) Q MI compared with 20 % ( 20 out of 100 , p = 0.005 ) taking dipyridamole with aspirin and 19 % ( 20 out of 105 on placebo , p = 0.006 ) . Infa rct ions of patients treated with heparin as assessed by peak of serum creatine kinase ( CK ) were also smaller ( 810 + /- 538 IU/1 ) than in groups taking antiplatelets ( 1229 + /- 829 IU/1 , p = 10.048 ) or placebo ( 1417 + /- 919 IU/1 , p = 0.009 ) . We defined a subgroup at high risk patients who had prolonged chest pain longer than 45 min and ECG changes with ST segment depression more than 1 mm within 6 hours of admission : 55 % of these patients developed acute infa rct ion in the following 72 hours . Aggressive management including coronary angiography and fibrinolysis should be considered in well equipped centers for patients with evolving coronary thrombus in a general hospital , heparin infusion should be part of routine treatment as patients on heparin developed smaller infa rct ions OBJECTIVES The aims of the Safety and Efficacy of Subcutaneous Enoxaparin Versus Intravenous Unfractionated Heparin and Tirofiban Versus Placebo in the Treatment of Acute ST-Segment Elevation Myocardial Infa rct ion Patients Ineligible for Reperfusion ( TETAMI ) study were to demonstrate that enoxaparin was superior to unfractionated heparin ( UFH ) and that tirofiban was better than placebo in patients with acute ST-segment elevation myocardial infa rct ion ( STEMI ) who do not receive timely reperfusion . BACKGROUND An optimal treatment strategy has not been identified for the many STEMI patients ineligible for acute reperfusion . METHODS A total of 1224 patients were enrolled in 91 centers in 14 countries between July 1999 and July 2002 . Patients with STEMI ineligible for reperfusion were r and omized to enoxaparin , enoxaparin plus tirofiban , UFH , or UFH plus tirofiban . All patients received oral aspirin . The primary efficacy end point was the 30-day combined incidence of death , reinfa rct ion , or recurrent angina ; the primary analysis was the comparison of the pooled enoxaparin and UFH groups . RESULTS The incidence of the primary efficacy end point was 15.7 % enoxaparin versus 17.3 % for UFH ( odds ratio 0.89 [ 95 % confidence interval CI = 0.66 to 1.21 ] ) and 16.6 % for tirofiban versus 16.4 % for placebo ( odds ratio 1.02 [ 95 % CI 0.75 to 1.38 ] ) . The Thrombolysis In Myocardial Infa rct ion ( TIMI ) major hemorrhage rate was 1.5 % for enoxaparin versus 1.3 % for UFH ( odds ratio 1.16 [ 95 % CI 0.44 to 3.02 ] ) and 1.8 % versus 1 % for tirofiban versus placebo ( odds ratio 1.82 [ 95 % CI 0.6 
    Output:
    
Compared with placebo , patients treated with heparins had a similar risk of mortality , revascularization , recurrent angina , and thrombocytopenia .
However , those treated with heparins had a decreased risk of myocardial infa rct ion and a higher incidence of minor bleeding .