***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: 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 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 BACKGROUND Heparin is an effective , widely used treatment for unstable angina . Among patients enrolled in a double-blind , r and omized , placebo-controlled trial comparing intravenous heparin , aspirin , both treatments , and neither during the acute phase of unstable angina , we encountered patients in whom unstable angina was reactivated after heparin was discontinued . METHODS The study population included 403 of the original 479 patients in the trial who had completed six days of blinded therapy without refractory angina or myocardial infa rct ion . After the discontinuation of therapy , clinical events , including reactivation of unstable angina and myocardial infa rct ion occurring within 96 hours after hospitalization , were closely monitored . RESULTS Early reactivation occurred in 14 of the 107 patients who received heparin alone , as compared with only 5 patients in each of the other three study groups ( P less than 0.01 ) . These reactivations required urgent intervention ( thrombolysis , angioplasty , or coronary-bypass surgery ) in 11 patients treated with heparin alone , but in only 2 patients in the other groups combined ( P less than 0.01 ) . Four of the six patients who had a myocardial infa rct ion during a reactivation of their disease were in the heparin group . Reactivations in this group occurred in a cluster a mean ( + /- SD ) of 9.5 + /- 5 hours after the discontinuation of the study drug but were r and omly distributed over the initial 96 hours in the other three groups . CONCLUSIONS Although heparin is beneficial in treating unstable angina , the disease process may be reactivated within hours of the discontinuation of this drug . Concomitant therapy with aspirin may prevent this withdrawal phenomenon The FRISC II study addressed two key questions in the management of acute coronary syndromes : is it beneficial to extend low‐molecular‐weight heparin ( LMWH ) therapy with dalteparin beyond the initial period of acute treatment ; and , is a strategy of early invasive therapy , including angioplasty and surgical revascularization , preferable to a more conservative strategy ? The study focused on patients with unstable coronary artery disease ( UCAD ) , that is , angina and non‐ST‐segment‐elevation myocardial infa rct ion ( MI ) . Patients were allocated in a r and omized , factorial study design to either an invasive or a conservative management strategy . Within each of these groups , patients were further r and omized to receive either 3 months of extended treatment with dalteparin or placebo , following at least 5 days ' treatment with open‐label dalteparin . After 1 year , patient survival and MI‐free survival were significantly higher in the invasive therapy group than in the noninvasive group . Patients who received extended dalteparin treatment had a significantly reduced probability of death or MI after 1 month ( relative risk reduction 47 % ; p = 0.002 ) , a benefit still evident after 60 days , but after 3 months there was no longer any significant clinical advantage compared with placebo . There was , however , a significant reduction in the combined incidence of death , MI , or revascularization at 3 months in the extended dalteparin treatment group ( relative risk reduction 13 % ; p = 0.031 ) . The benefits of extended dalteparin treatment were particularly marked in patients with elevated troponin‐T or ST‐segment depression . A subgroup analysis of conservatively managed patients who underwent revascularization in the first 45 days revealed that the probability of death or MI at 1 year was significantly lower among patients who received extended dalteparin treatment ( relative risk reduction 35 % ; p = 0.02 ) . Extended dalteparin treatment is , however , associated with a small increase in bleeding risk . in conclusion , early invasive therapy ( following combined treatment with aspirin and dalteparin ) is recommended in a majority of patients with UCAD . Furthermore , extended dalteparin treatment for up to 45 days is efficacious and well tolerated , and therefore provides a useful “ bridge ” to revascularization when early revascularization is not immediately available Increased thrombin generation is frequently associated with an increase in  anginal activity .  A cross-over , single-blind , completely r and omized study was planned in order to evaluate whether the control of thrombin generation affected the increase in anginal activity . After discharge from the hospital , 24 patients ( 18 men and 6 women , aged 40 to 69 years ) suffering from spontaneous angina were followed up to 12 months and were alternatively treated during two consecutive 6-month periods with calcium heparin , 12,500 IU by the subcutaneous route , or with placebo by the intramuscular route , in addition to the usual antianginal medications . Thrombin generation and clinical activity of angina were assessed every 15 days by measuring fibrinopeptide A ( FPA ) plasma levels and by grading in three classes ( symptomless , mildly symptomatic , and severely symptomatic ) the anginal activity on the basis of the number and the time concentration of the ischemic attacks and ECG changes . Low-dose heparin treatment significantly reduced both the FPA plasma level ( from 4.1 + /- 3.7 to 2.3 + /- 1.8 ng/ml , p less than 0.001 ) and the clinical activity of angina . During heparin treatment , the frequency of the observations in the severely and mildly symptomatic classes decreased , respectively , by 53 % and by 30 % , whereas that in the symptomless class increased by 23 % ( p less than 0.001 ) in comparison with the period on placebo . Present results indicate that the control of thrombin generation obtained by low-dose heparin treatment favorably affects the degree of anginal activity in patients with spontaneous angina OBJECTIVES This study compared the effects of heparin and aspirin versus aspirin alone on transient myocardial ischemia and in-hospital prognosis in patients with unstable angina . BACKGROUND Transient myocardial ischemia occurring in patients with unstable angina is associated with an adverse prognosis . Heparin and aspirin are two drugs used frequently in the treatment of this condition , but the effect of combination therapy versus aspirin alone on transient myocardial ischemia is unknown . METHODS Two hundred eighty-five consecutive patients with unstable angina were r and omized to receive either intravenous heparin plus oral aspirin ( 150 mg once daily ) ( Group H + A ) or aspirin alone ( Group A ) . Patients also received a beta-adrenergic blocking agent , diltiazem and intravenous nitrates . ST segment monitoring was performed for the 1st 48 h of treatment . Patients were followed up for the duration of their in-hospital stay . RESULTS One hundred fifty-four patients ( 30 women , mean [ + /- SEM ] age 58.3 + /- 0.8 years ) received heparin and aspirin ( Group H + A ) , and 131 patients ( 26 women , mean age 60.6 + /- 0.8 years ) received aspirin only ( Group A ) . ST segment monitoring ( 11,622 h ) yielded 244 episodes of transient myocardial ischemia of a total duration of 7,819 min . There were no significant differences between the two treatment arms in the number of patients with transient myocardial ischemia ( 27 [ 18 % ] in Group H + A vs. 31 [ 24 % ] in Group A ) , number of episodes ( 96 in Group H + A vs. 148 in Group A ) or total duration of transient myocardial ischemia ( 2,911 min in Group H + A vs. 4,908 min in Group A ) . The incidence of in-hospital myocardial infa rct ion or death was significantly higher in patients with transient myocardial ischemia ( 53 % vs. 22 % , p < 0.0001 ) . Five of the six deaths occurred in patients with transient myocardial ischemia . Event-free survival from myocardial infa rct ion or death was similar in both treatment groups . Preadmission therapy with aspirin was associated with a lower in-hospital infa rct ion rate ( 19 % vs. 34 % , p = 0.01 ) . CONCLUSIONS The presence of transient myocardial ischemia in patients with unstable angina is associated with a significantly higher incidence of myocardial infa rct ion or death in hospital . Combined therapy with heparin and aspirin compared with aspirin alone makes no difference in the development of these events , nor does it reduce the development of transient myocardial ischemia BACKGROUND The purpose of this study was to compare combination antithrombotic therapy with aspirin plus anticoagulation versus aspirin alone , when added to conventional antianginal therapy in patients with unstable rest angina or non-Q-wave myocardial infa rct ion who were nonprior aspirin users . METHODS AND RESULTS Two hundred fourteen patients were r and omized ; 109 were r and omized to receive aspirin alone  ( 162.5 mg daily ) and 105 to receive a combination of aspirin plus anticoagulation , ie , aspirin 162.5 mg daily plus heparin ( activated partial thromboplastin time , two times control ) followed by aspirin 162.5 mg daily plus warfarin ( international normalized ratio , 2 to 3 ) . Trial therapy was begun by 9.5 + /- 8.8 hours of qualifying pain and was continued for 12 weeks . Primary end points were recurrent angina with ECG changes , myocardial infa rct ion , and /or death . Analysis by intention to treat of primary events at 12 weeks was performed . At 14 days , there was a significant reduction in total ischemic events in the combination group versus aspirin alone ( 10.5 % versus 27 % , P = .004 ) . An efficacy analysis of primary events at 12 weeks also revealed a large reduction in total ischemic events in the combination group versus aspirin alone ( 13 % versus 25 % , P = .06 ) . Bleeding complications were slightly more common with combination therapy . CONCL 
    Output:
    
Compared to placebo , patients treated with heparins had similar risk of mortality , revascularization , recurrent angina , major bleeding and thrombocytopenia .
However , those treated with heparins had decreased risk of MI and a higher incidence of minor bleeding