human
***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 — Chronic heart failure remains a major cause of mortality and morbidity . The role of antithrombotic therapy in patients with chronic heart failure has long been debated . The objective of this study was to determine the optimal antithrombotic agent for heart failure patients with reduced ejection fractions who are in sinus rhythm . Methods and Results — This prospect i ve , r and omized clinical trial of open-label warfarin ( target international normalized ratio of 2.5 to 3.0 ) and double-blind treatment with either aspirin ( 162 mg once daily ) or clopidogrel ( 75 mg once daily ) had a 30-month enrollment period and a minimum of 12 months of treatment . We enrolled 1587 men and women ≥18 years of age with symptomatic heart failure for at least 3 months who were in sinus rhythm and had left ventricular ejection fraction of ≤35 % . The primary outcome was the time to first occurrence of death , nonfatal myocardial infa rct ion , or nonfatal stroke . For the primary composite end point , the hazard ratios were as follows : for warfarin versus aspirin , 0.98 ( 95 % CI , 0.86 to 1.12 ; P=0.77 ) ; for clopidogrel versus aspirin , 1.08 ( 95 % CI , 0.83 to 1.40 ; P=0.57 ) ; and for warfarin versus clopidogrel , 0.89 ( 95 % CI , 0.68 to 1.16 ; P=0.39 ) . Warfarin was associated with fewer nonfatal strokes than aspirin or clopidogrel  . Hospitalization for worsening heart failure occurred in 116 ( 22.2 % ) , 97 ( 18.5 % ) , and 89 ( 16.5 % ) patients treated with aspirin , clopidogrel , and warfarin , respectively ( P=0.02 for warfarin versus aspirin ) . Conclusion — The primary outcome measure and the mortality data do not support the primary hypotheses that warfarin is superior to aspirin and that clopidogrel is superior to aspirin BACKGROUND Milrinone , a phosphodiesterase inhibitor , enhances cardiac contractility by increasing intracellular levels of cyclic AMP , but the long-term effect of this type of positive inotropic agent on the survival of patients with chronic heart failure has not been determined . METHODS We r and omly assigned 1,088 patients with severe chronic heart failure ( New York Heart Association class III or IV ) and advanced left ventricular dysfunction to double-blind treatment with  ( 40 mg of oral milrinone daily ( 561 patients ) or placebo ( 527 patients ) . In addition , all patients received conventional therapy with digoxin , diuretics , and a converting-enzyme inhibitor throughout the trial . The median period of follow-up was 6.1 months ( range , 1 day to 20 months ) . RESULTS As compared with placebo , milrinone therapy was associated with a 28 percent increase in mortality from all causes ( 95 percent confidence interval , 1 to 61 percent ; P = 0.038 ) and a 34 percent increase in cardiovascular mortality ( 95 percent confidence interval , 6 to 69 percent ; P = 0.016 ) . The adverse effect of milrinone was greatest in patients with the most severe symptoms ( New York Heart Association class IV ) , who had a 53 percent increase in mortality ( 95 percent confidence interval , 13 to 107 percent ; P = 0.006 ) . Milrinone did not have a beneficial effect on the survival of any subgroup . Patients treated with milrinone had more hospitalizations ( 44 vs. 39 percent , P = 0.041 ) , were withdrawn from double-blind therapy more frequently ( 12.7 vs. 8.7 percent , P = 0.041 ) , and had serious adverse cardiovascular reactions , including hypotension ( P = 0.006 ) and syncope ( P = 0.002 ) , more often than the patients given placebo . CONCLUSIONS Our findings indicate that despite its beneficial hemodynamic actions , long-term therapy with oral milrinone increases the morbidity and mortality of patients with severe chronic heart failure . The mechanism by which the drug exerts its deleterious effects is unknown BACKGROUND Heart failure is commonly associated with vascular disease and a high rate of athero-thrombotic events , but the risks and benefits of antithrombotic therapy are unknown . METHODS The current study was an open-label , r and omized , controlled trial comparing no antithrombotic therapy , aspirin ( 300 mg/day ) , and warfarin ( target international normalized ratio 2.5 ) in patients with heart failure and left ventricular systolic dysfunction requiring diuretic therapy . The primary objective was to demonstrate the feasibility and inform the design of a larger outcome study . The primary clinical outcome was death , nonfatal myocardial infa rct ion , or nonfatal stroke . RESULTS Two hundred seventy-nine patients were r and omized and 627 patient-years exposure were accumulated over a mean follow-up time of 27 + /- 1 months . Twenty-six ( 26 % ) , 29 ( 32 % ) , and 23 ( 26 % ) patients r and omized to no antithrombotic treatment , aspirin , and warfarin , respectively , reached the primary outcome ( ns ) . There were trends to a worse outcome among those r and omized to aspirin for a number of secondary outcomes . Significantly ( P = .044 ) more patients r and omized to aspirin were hospitalized for cardiovascular reasons , especially worsening heart failure . CONCLUSIONS The Warfarin/Aspirin Study in Heart failure ( WASH ) provides no evidence that aspirin is effective or safe in patients with heart failure . The benefits of warfarin for patients with heart failure in sinus rhythm have not been established . Antithrombotic therapy in patients with heart failure is not evidence based but commonly contributes to polypharmacy BACKGROUND In patients who have had a myocardial infa rct ion , the long-term risk of stroke and its relation to the extent of left ventricular dysfunction have not been determined . We studied whether a reduced left ventricular ejection fraction is associated with an increased risk of stroke after myocardial infa rct ion and whether other factors such as older age and therapy with anticoagulants , thrombolytic agents , or captopril affect long-term rates of stroke . METHODS We performed an observational analysis of prospect ively collected data on 2231 patients who had left ventricular dysfunction after acute myocardial infa rct ion who were enrolled in the Survival and Ventricular Enlargement trial . The mean follow-up was 42 months . Risk factors for stroke were assessed by both univariate and multivariate Cox proportional-hazards analysis . RESULTS Among these patients , 103 ( 4.6 percent ) had fatal or nonfatal strokes during the study ( rate of stroke per year of follow-up , 1.5 percent ) . The estimated five-year rate of stroke in all the patients was 8.1 percent . As compared with patients without stroke , patients with stroke were older ( mean [ + /-SD ] age , 63+/-9 years vs. 59+/-11 years ; P<0.001 ) and had lower ejection fractions ( 29+/-7 percent vs. 31+/-7 percent , P=0.01 ) . Independent risk factors for stroke included a lower ejection fraction ( for every decrease of 5 percentage points in the ejection fraction there was an 18 percent increase in the risk of stroke ) , older age , and the absence of aspirin or anticoagulant therapy . Patients with ejection fractions of < or = 28 percent after myocardial infa rct ion had a relative risk of stroke of 1.86 , as compared with patients with ejection fractions of more than 35 percent ( P=0.01 ) . The use of thrombolytic agents and captopril had no significant effect on the risk of stroke . CONCLUSIONS During the five years after myocardial infa rct ion , patients have a substantial risk of stroke . A decreased ejection fraction and older age are both independent predictors of an increased risk of stroke .  Anticoagulant therapy appears to have a protective effect against stroke after myocardial infa rct ion Background The incidence of thromboembolism and the benefit of anticoagulation in congestive heart failure are controversial . Methods and Results The data base provided by the Veterans Affairs Vasodilator-Heart Failure Trials ( V-HeFT I and II ) was examined retrospectively to address these issues . In V-HeFT I , 642 men with heart failure were followed an average of 2.28 years , providing 1,464 patient-years of follow-up . In V-HeFT II , 804 men were followed an average of 2.56 years , with 2,061 patient-years of follow-up . Mean left ventricular ejection fraction was 30%o in V-HeFT I and 29 % in V-HeFT II . Functional capacity was at the interface of classes II and III with a peak exercise oxygen consumption of 14.7 mL. kg -1 . min-1 in V-HeFT I and 13.7 mL- kg-1 min-1 in V-HeFT II . Warfarin and antiplatelet agents were administered at the discretion of individual investigators . The incidence of all thromboembolic events during 1,068 patient-years without warfarin in V-HeFIT I was 2.7/100 patient-years and during 1,188 patient-years in V-HeFT II was 2.1/100 patient-years and was not reduced in patients treated with warfarin . Patients experiencing events had a lower peak exercise oxygen consumption ( P<0.03 in V-HeFT I and P<0.001 in V-HeFT II ) and a lower mean ejection fraction ( P=0.10 in V-HeFT I and P=0.07 in V-HeFT II ) . Atrial fibrillation was not associated with an increased risk of thromboembolic events . Conclusions The incidence of thromboembolism and stroke in class II or III congestive heart failure is not high and may not be significantly reduced with warfarin treatment . Routine use of anticoagulants in patients with heart failure may not be justified Data from epidemiologic , autopsy , Holter monitoring , and electrophysiologic studies support the hypothesis that acute myocardial ischemia , even in the absence of myocardial infa rct ion , is a critical component of the pathophysiology of sudden coronary death . Acute myocardial ischemia superimposed upon ventricles damaged from previous infa rct ions has been demonstrated to enhance the generation of lethal ventricular arrhythmias . This is a retrospective analysis of 6,797 participants in the Studies of Left Ventricular Dysfunction prevention and treatment trials . Both univariate and multivariate Cox proportional-hazards modeling were used to study the association of anticoagulant and antiplatelet therapy with the risk for sudden cardiac death . The following covariates were adjusted for in the analysis : age , ejection fraction , gender , atrial fibrillation , diabetes , a history of angina , prior infa rct ion , prior revascularization , and the regular use of beta blockers , diuretics , digoxin , antiarrhythmic agents , or enalapril . The overall incidence of sudden cardiac death per 100 patient-years of follow-up was 2.24 % . In multivariate analysis , antiplatelet and anticoagulant monotherapy each remained independently associated with a reduction in the risk of sudden cardiac death :  antiplatelet therapy with a 24 % reduction ( relative risk [ RR ] 0.76 ; 95 % confidence interval [ CI ] 0.61 - 0.95 ) and antiplatelet monotherapy with a 32 % reduction ( RR 0.68 ; 95 % CI 0.48 - 0.96 ) . Thus , in patients with moderate to severe left ventricular systolic dysfunction result ing from coronary artery disease , antiplatelet and anticoagulant therapy are each associated with a reduction in the risk of sudden cardiac death BACKGROUND In patients with congestive heart failure ( CHF ) , clinical trials have demonstrated the benefit of a number of drugs on morbidity and mortality . Nevertheless so far , there is no published controlled study of long-term antithrombotic therapy in patients with CHF . The aim of this work was to identify the relationship between cardiovascular drug use , especially antithrombotic therapy , and survival of CHF patients in current clinical practice , using an observational , population -based data base . METHODS The EPICAL study ( Epidémiologie de l'Insuffisance Cardiaque Avancée en Lorraine ) has identified prospect ively all patients with severe CHF in the community of Lorraine . Inclusion criteria were age 20 - 80 years in 1994 , at least one hospitalisation for cardiac decompensation , NYHA III/IV HF , ventricular ejection fraction < or = 30 % or cardiothoracic index > or = 60 % and arterial hypotension or peripheral and /or pulmonary oedema . A total of 417 consecutive patients surviving at hospital discharge were included in the data base . The average follow-up period was 5 years . Univariate Cox models were used to test the relationship of baseline biological and clinical factors to survival .  Cardiovascular drug prescriptions were tested in a multivariate Cox model adjusted by other known predictive factors . RESULTS Duration 
    Output:
    
agent
At present , there are no data on the role of oral anticoagulation versus antiplatelet agents in heart failure with preserved ejection fraction with sinus rhythm .
Also , there were no data from RCTs on the utility of non-vitamin K antagonist oral anticoagulants compared to antiplatelet agents in heart failure with sinus rhythm
***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 — Chronic heart failure remains a major cause of mortality and morbidity . The role of antithrombotic therapy in patients with chronic heart failure has long been debated . The objective of this study was to determine the optimal antithrombotic agent for heart failure patients with reduced ejection fractions who are in sinus rhythm . Methods and Results — This prospect i ve , r and omized clinical trial of open-label warfarin ( target international normalized ratio of 2.5 to 3.0 ) and double-blind treatment with either aspirin ( 162 mg once daily ) or clopidogrel ( 75 mg once daily ) had a 30-month enrollment period and a minimum of 12 months of treatment . We enrolled 1587 men and women ≥18 years of age with symptomatic heart failure for at least 3 months who were in sinus rhythm and had left ventricular ejection fraction of ≤35 % . The primary outcome was the time to first occurrence of death , nonfatal myocardial infa rct ion , or nonfatal stroke . For the primary composite end point , the hazard ratios were as follows : for warfarin versus aspirin , 0.98 ( 95 % CI , 0.86 to 1.12 ; P=0.77 ) ; for clopidogrel versus aspirin , 1.08 ( 95 % CI , 0.83 to 1.40 ; P=0.57 ) ; and for warfarin versus clopidogrel , 0.89 ( 95 % CI , 0.68 to 1.16 ; P=0.39 ) . Warfarin was associated with fewer nonfatal strokes than aspirin or clopidogrel  . Hospitalization for worsening heart failure occurred in 116 ( 22.2 % ) , 97 ( 18.5 % ) , and 89 ( 16.5 % ) patients treated with aspirin , clopidogrel , and warfarin , respectively ( P=0.02 for warfarin versus aspirin ) . Conclusion — The primary outcome measure and the mortality data do not support the primary hypotheses that warfarin is superior to aspirin and that clopidogrel is superior to aspirin BACKGROUND Milrinone , a phosphodiesterase inhibitor , enhances cardiac contractility by increasing intracellular levels of cyclic AMP , but the long-term effect of this type of positive inotropic agent on the survival of patients with chronic heart failure has not been determined . METHODS We r and omly assigned 1,088 patients with severe chronic heart failure ( New York Heart Association class III or IV ) and advanced left ventricular dysfunction to double-blind treatment with  ( 40 mg of oral milrinone daily ( 561 patients ) or placebo ( 527 patients ) . In addition , all patients received conventional therapy with digoxin , diuretics , and a converting-enzyme inhibitor throughout the trial . The median period of follow-up was 6.1 months ( range , 1 day to 20 months ) . RESULTS As compared with placebo , milrinone therapy was associated with a 28 percent increase in mortality from all causes ( 95 percent confidence interval , 1 to 61 percent ; P = 0.038 ) and a 34 percent increase in cardiovascular mortality ( 95 percent confidence interval , 6 to 69 percent ; P = 0.016 ) . The adverse effect of milrinone was greatest in patients with the most severe symptoms ( New York Heart Association class IV ) , who had a 53 percent increase in mortality ( 95 percent confidence interval , 13 to 107 percent ; P = 0.006 ) . Milrinone did not have a beneficial effect on the survival of any subgroup . Patients treated with milrinone had more hospitalizations ( 44 vs. 39 percent , P = 0.041 ) , were withdrawn from double-blind therapy more frequently ( 12.7 vs. 8.7 percent , P = 0.041 ) , and had serious adverse cardiovascular reactions , including hypotension ( P = 0.006 ) and syncope ( P = 0.002 ) , more often than the patients given placebo . CONCLUSIONS Our findings indicate that despite its beneficial hemodynamic actions , long-term therapy with oral milrinone increases the morbidity and mortality of patients with severe chronic heart failure . The mechanism by which the drug exerts its deleterious effects is unknown BACKGROUND Heart failure is commonly associated with vascular disease and a high rate of athero-thrombotic events , but the risks and benefits of antithrombotic therapy are unknown . METHODS The current study was an open-label , r and omized , controlled trial comparing no antithrombotic therapy , aspirin ( 300 mg/day ) , and warfarin ( target international normalized ratio 2.5 ) in patients with heart failure and left ventricular systolic dysfunction requiring diuretic therapy . The primary objective was to demonstrate the feasibility and inform the design of a larger outcome study . The primary clinical outcome was death , nonfatal myocardial infa rct ion , or nonfatal stroke . RESULTS Two hundred seventy-nine patients were r and omized and 627 patient-years exposure were accumulated over a mean follow-up time of 27 + /- 1 months . Twenty-six ( 26 % ) , 29 ( 32 % ) , and 23 ( 26 % ) patients r and omized to no antithrombotic treatment , aspirin , and warfarin , respectively , reached the primary outcome ( ns ) . There were trends to a worse outcome among those r and omized to aspirin for a number of secondary outcomes . Significantly ( P = .044 ) more patients r and omized to aspirin were hospitalized for cardiovascular reasons , especially worsening heart failure . CONCLUSIONS The Warfarin/Aspirin Study in Heart failure ( WASH ) provides no evidence that aspirin is effective or safe in patients with heart failure . The benefits of warfarin for patients with heart failure in sinus rhythm have not been established . Antithrombotic therapy in patients with heart failure is not evidence based but commonly contributes to polypharmacy BACKGROUND In patients who have had a myocardial infa rct ion , the long-term risk of stroke and its relation to the extent of left ventricular dysfunction have not been determined . We studied whether a reduced left ventricular ejection fraction is associated with an increased risk of stroke after myocardial infa rct ion and whether other factors such as older age and therapy with anticoagulants , thrombolytic agents , or captopril affect long-term rates of stroke . METHODS We performed an observational analysis of prospect ively collected data on 2231 patients who had left ventricular dysfunction after acute myocardial infa rct ion who were enrolled in the Survival and Ventricular Enlargement trial . The mean follow-up was 42 months . Risk factors for stroke were assessed by both univariate and multivariate Cox proportional-hazards analysis . RESULTS Among these patients , 103 ( 4.6 percent ) had fatal or nonfatal strokes during the study ( rate of stroke per year of follow-up , 1.5 percent ) . The estimated five-year rate of stroke in all the patients was 8.1 percent . As compared with patients without stroke , patients with stroke were older ( mean [ + /-SD ] age , 63+/-9 years vs. 59+/-11 years ; P<0.001 ) and had lower ejection fractions ( 29+/-7 percent vs. 31+/-7 percent , P=0.01 ) . Independent risk factors for stroke included a lower ejection fraction ( for every decrease of 5 percentage points in the ejection fraction there was an 18 percent increase in the risk of stroke ) , older age , and the absence of aspirin or anticoagulant therapy . Patients with ejection fractions of < or = 28 percent after myocardial infa rct ion had a relative risk of stroke of 1.86 , as compared with patients with ejection fractions of more than 35 percent ( P=0.01 ) . The use of thrombolytic agents and captopril had no significant effect on the risk of stroke . CONCLUSIONS During the five years after myocardial infa rct ion , patients have a substantial risk of stroke . A decreased ejection fraction and older age are both independent predictors of an increased risk of stroke .  Anticoagulant therapy appears to have a protective effect against stroke after myocardial infa rct ion Background The incidence of thromboembolism and the benefit of anticoagulation in congestive heart failure are controversial . Methods and Results The data base provided by the Veterans Affairs Vasodilator-Heart Failure Trials ( V-HeFT I and II ) was examined retrospectively to address these issues . In V-HeFT I , 642 men with heart failure were followed an average of 2.28 years , providing 1,464 patient-years of follow-up . In V-HeFT II , 804 men were followed an average of 2.56 years , with 2,061 patient-years of follow-up . Mean left ventricular ejection fraction was 30%o in V-HeFT I and 29 % in V-HeFT II . Functional capacity was at the interface of classes II and III with a peak exercise oxygen consumption of 14.7 mL. kg -1 . min-1 in V-HeFT I and 13.7 mL- kg-1 min-1 in V-HeFT II . Warfarin and antiplatelet agents were administered at the discretion of individual investigators . The incidence of all thromboembolic events during 1,068 patient-years without warfarin in V-HeFIT I was 2.7/100 patient-years and during 1,188 patient-years in V-HeFT II was 2.1/100 patient-years and was not reduced in patients treated with warfarin . Patients experiencing events had a lower peak exercise oxygen consumption ( P<0.03 in V-HeFT I and P<0.001 in V-HeFT II ) and a lower mean ejection fraction ( P=0.10 in V-HeFT I and P=0.07 in V-HeFT II ) . Atrial fibrillation was not associated with an increased risk of thromboembolic events . Conclusions The incidence of thromboembolism and stroke in class II or III congestive heart failure is not high and may not be significantly reduced with warfarin treatment . Routine use of anticoagulants in patients with heart failure may not be justified Data from epidemiologic , autopsy , Holter monitoring , and electrophysiologic studies support the hypothesis that acute myocardial ischemia , even in the absence of myocardial infa rct ion , is a critical component of the pathophysiology of sudden coronary death . Acute myocardial ischemia superimposed upon ventricles damaged from previous infa rct ions has been demonstrated to enhance the generation of lethal ventricular arrhythmias . This is a retrospective analysis of 6,797 participants in the Studies of Left Ventricular Dysfunction prevention and treatment trials . Both univariate and multivariate Cox proportional-hazards modeling were used to study the association of anticoagulant and antiplatelet therapy with the risk for sudden cardiac death . The following covariates were adjusted for in the analysis : age , ejection fraction , gender , atrial fibrillation , diabetes , a history of angina , prior infa rct ion , prior revascularization , and the regular use of beta blockers , diuretics , digoxin , antiarrhythmic agents , or enalapril . The overall incidence of sudden cardiac death per 100 patient-years of follow-up was 2.24 % . In multivariate analysis , antiplatelet and anticoagulant monotherapy each remained independently associated with a reduction in the risk of sudden cardiac death :  antiplatelet therapy with a 24 % reduction ( relative risk [ RR ] 0.76 ; 95 % confidence interval [ CI ] 0.61 - 0.95 ) and antiplatelet monotherapy with a 32 % reduction ( RR 0.68 ; 95 % CI 0.48 - 0.96 ) . Thus , in patients with moderate to severe left ventricular systolic dysfunction result ing from coronary artery disease , antiplatelet and anticoagulant therapy are each associated with a reduction in the risk of sudden cardiac death BACKGROUND In patients with congestive heart failure ( CHF ) , clinical trials have demonstrated the benefit of a number of drugs on morbidity and mortality . Nevertheless so far , there is no published controlled study of long-term antithrombotic therapy in patients with CHF . The aim of this work was to identify the relationship between cardiovascular drug use , especially antithrombotic therapy , and survival of CHF patients in current clinical practice , using an observational , population -based data base . METHODS The EPICAL study ( Epidémiologie de l'Insuffisance Cardiaque Avancée en Lorraine ) has identified prospect ively all patients with severe CHF in the community of Lorraine . Inclusion criteria were age 20 - 80 years in 1994 , at least one hospitalisation for cardiac decompensation , NYHA III/IV HF , ventricular ejection fraction < or = 30 % or cardiothoracic index > or = 60 % and arterial hypotension or peripheral and /or pulmonary oedema . A total of 417 consecutive patients surviving at hospital discharge were included in the data base . The average follow-up period was 5 years . Univariate Cox models were used to test the relationship of baseline biological and clinical factors to survival .  Cardiovascular drug prescriptions were tested in a multivariate Cox model adjusted by other known predictive factors . RESULTS Duration 
    Output:
    