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: PURPOSE To determine the incidence of major bleeding in out patients treated with warfarin  and to identify predictive factors known at the start of therapy . PATIENTS AND METHODS The records of 565 patients starting outpatient therapy with warfarin upon discharge from a university hospital were review ed . Follow-up information was obtained for 562 patients ( 99.5 % ) .  Bleeding was classified as major or minor using explicit criteria . The cumulative incidence of bleeding was estimated by means of survival analysis . Independent risk factors for major bleeding were identified using Cox regression analysis in 375 r and omly chosen patients ; they were tested in the remaining 187 patients . RESULTS Major bleeding occurred in 65 patients ( 12 % ) and was fatal in 10 patients ( 2 % ) . The cumulative incidences of major bleeding at one , 12 , and 48 months were 3 % , 11 % , and 22 % , respectively . The monthly risk of major bleeding decreased over time , from 3 % during the first month of outpatient therapy to 0.3 % per month after the first year of therapy . Five independent risk factors for major bleeding -- age 65 years or greater , history of stroke , history of gastrointestinal bleeding , a serious comorbid condition ( recent myocardial infa rct ion , renal insufficiency , or severe anemia ) , atrial fibrillation -- predicted major bleeding in the testing group ; the cumulative incidence of major bleeding at 48 months was 2 % in 57 low-risk patients , 17 % in 110 middle-risk patients , and 63 % in 20 high-risk patients . CONCLUSION These findings provide a quantitative basis for evaluating the risk of major bleeding in individual patients at the start of outpatient therapy with warfarin . Whether the risk of bleeding can be reduced in high-risk patients without reducing the benefit of therapy remains to be determined OBJECTIVES We sought to evaluate the relation between warfarin anticoagulation and survival and morbidity from cardiac disease in patients with left ventricular ( LV ) dysfunction . BACKGROUND Warfarin anticoagulation plays a major role in the management of patients who have had a large myocardial infa rct ion and in those with atrial fibrillation . However , its use in patients with LV systolic dysfunction has been controversial . METHODS We review ed data on  warfarin use in 6,797 patients enrolled in the Studies of Left Ventricular Dysfunction ( SOLVD ) trial and analyzed the relation between warfarin use and all-cause mortality , as well as the combined end point of death or hospital admission for heart failure . We used Cox regression to adjust for differences in baseline characteristics and to test for the interaction between warfarin use and selected patient variables in relation to outcome . RESULTS On multivariate analysis , use of warfarin was associated with a significant reduction in all-cause mortality ( adjusted hazard ratio [ HR ] 0.76 , 95 % confidence interval [ CI ] 0.65 to 0.89 , p = 0.0006 ) and in the risk of death or hospital admission for heart failure ( HR 0.82 , 95 % CI 0.72 to 0.93 , p = 0.0002 ) . Risk reduction was observed when each trial or r and omization arm was analyzed separately , as well as in both genders . It was not significantly influenced by the presence of atrial fibrillation , age , ejection fraction , New York Heart Association functional class or etiology . CONCLUSIONS In patients with LV systolic dysfunction , warfarin use is associated with improved survival and reduced morbidity . This association is primarily due to a reduction in cardiac events and does not appear to be limited to any particular subgroup 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 To evaluate the influence of the angiotensin-converting-enzyme inhibitor enalapril ( 2.5 to 40 mg per day ) on the prognosis of severe congestive heart failure ( New York Heart Association [ NYHA ] functional class IV ) , we r and omly assigned 253 patients in a double-blind study to receive either placebo ( n = 126 ) or enalapril ( n = 127 ) . Conventional treatment for heart failure , including the use of other vasodilators , was continued in both groups . Follow-up averaged 188 days ( range , 1 day to 20 months ) . The crude mortality at the end of six months ( primary end point ) was 26 percent in the enalapril group and 44 percent in the placebo group -- a reduction of 40 percent ( P = 0.002 ) . Mortality was reduced by 31 percent at one year ( P = 0.001 ) . By the end of the study , there had been 68 deaths in the placebo group and 50 in the enalapril group -- a reduction of 27 percent ( P = 0.003 ) . The entire reduction in total mortality was found to be among patients with progressive heart failure ( a reduction of 50 percent ) , whereas no difference was seen in the incidence of sudden cardiac death . A significant improvement in NYHA classification was observed in the enalapril group , together with a reduction in heart size and a reduced requirement for other medication for heart failure . The overall withdrawal rate was similar in both groups , but hypotension requiring withdrawal occurred in seven patients in the enalapril group and in no patients in the placebo group . After the initial dose of enalapril was reduced to 2.5 mg daily in high-risk patients , this side effect was less frequent . We conclude that the addition of enalapril to conventional therapy in patients with severe congestive heart failure can reduce mortality and improve symptoms . The beneficial effect on mortality is due to a reduction in death from the progression of heart failure 
    Output:
    
agent
Limited evidence from r and omized trials and observational studies found a reduction in mortality and cardiovascular events with anticoagulants compared to controls .
Although oral anticoagulation is indicated in certain groups of patients with heart failure ( e.g. atrial fibrillation ) , the available data do not support its routine use in heart failure patients who remain in 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: PURPOSE To determine the incidence of major bleeding in out patients treated with warfarin  and to identify predictive factors known at the start of therapy . PATIENTS AND METHODS The records of 565 patients starting outpatient therapy with warfarin upon discharge from a university hospital were review ed . Follow-up information was obtained for 562 patients ( 99.5 % ) .  Bleeding was classified as major or minor using explicit criteria . The cumulative incidence of bleeding was estimated by means of survival analysis . Independent risk factors for major bleeding were identified using Cox regression analysis in 375 r and omly chosen patients ; they were tested in the remaining 187 patients . RESULTS Major bleeding occurred in 65 patients ( 12 % ) and was fatal in 10 patients ( 2 % ) . The cumulative incidences of major bleeding at one , 12 , and 48 months were 3 % , 11 % , and 22 % , respectively . The monthly risk of major bleeding decreased over time , from 3 % during the first month of outpatient therapy to 0.3 % per month after the first year of therapy . Five independent risk factors for major bleeding -- age 65 years or greater , history of stroke , history of gastrointestinal bleeding , a serious comorbid condition ( recent myocardial infa rct ion , renal insufficiency , or severe anemia ) , atrial fibrillation -- predicted major bleeding in the testing group ; the cumulative incidence of major bleeding at 48 months was 2 % in 57 low-risk patients , 17 % in 110 middle-risk patients , and 63 % in 20 high-risk patients . CONCLUSION These findings provide a quantitative basis for evaluating the risk of major bleeding in individual patients at the start of outpatient therapy with warfarin . Whether the risk of bleeding can be reduced in high-risk patients without reducing the benefit of therapy remains to be determined OBJECTIVES We sought to evaluate the relation between warfarin anticoagulation and survival and morbidity from cardiac disease in patients with left ventricular ( LV ) dysfunction . BACKGROUND Warfarin anticoagulation plays a major role in the management of patients who have had a large myocardial infa rct ion and in those with atrial fibrillation . However , its use in patients with LV systolic dysfunction has been controversial . METHODS We review ed data on  warfarin use in 6,797 patients enrolled in the Studies of Left Ventricular Dysfunction ( SOLVD ) trial and analyzed the relation between warfarin use and all-cause mortality , as well as the combined end point of death or hospital admission for heart failure . We used Cox regression to adjust for differences in baseline characteristics and to test for the interaction between warfarin use and selected patient variables in relation to outcome . RESULTS On multivariate analysis , use of warfarin was associated with a significant reduction in all-cause mortality ( adjusted hazard ratio [ HR ] 0.76 , 95 % confidence interval [ CI ] 0.65 to 0.89 , p = 0.0006 ) and in the risk of death or hospital admission for heart failure ( HR 0.82 , 95 % CI 0.72 to 0.93 , p = 0.0002 ) . Risk reduction was observed when each trial or r and omization arm was analyzed separately , as well as in both genders . It was not significantly influenced by the presence of atrial fibrillation , age , ejection fraction , New York Heart Association functional class or etiology . CONCLUSIONS In patients with LV systolic dysfunction , warfarin use is associated with improved survival and reduced morbidity . This association is primarily due to a reduction in cardiac events and does not appear to be limited to any particular subgroup 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 To evaluate the influence of the angiotensin-converting-enzyme inhibitor enalapril ( 2.5 to 40 mg per day ) on the prognosis of severe congestive heart failure ( New York Heart Association [ NYHA ] functional class IV ) , we r and omly assigned 253 patients in a double-blind study to receive either placebo ( n = 126 ) or enalapril ( n = 127 ) . Conventional treatment for heart failure , including the use of other vasodilators , was continued in both groups . Follow-up averaged 188 days ( range , 1 day to 20 months ) . The crude mortality at the end of six months ( primary end point ) was 26 percent in the enalapril group and 44 percent in the placebo group -- a reduction of 40 percent ( P = 0.002 ) . Mortality was reduced by 31 percent at one year ( P = 0.001 ) . By the end of the study , there had been 68 deaths in the placebo group and 50 in the enalapril group -- a reduction of 27 percent ( P = 0.003 ) . The entire reduction in total mortality was found to be among patients with progressive heart failure ( a reduction of 50 percent ) , whereas no difference was seen in the incidence of sudden cardiac death . A significant improvement in NYHA classification was observed in the enalapril group , together with a reduction in heart size and a reduced requirement for other medication for heart failure . The overall withdrawal rate was similar in both groups , but hypotension requiring withdrawal occurred in seven patients in the enalapril group and in no patients in the placebo group . After the initial dose of enalapril was reduced to 2.5 mg daily in high-risk patients , this side effect was less frequent . We conclude that the addition of enalapril to conventional therapy in patients with severe congestive heart failure can reduce mortality and improve symptoms . The beneficial effect on mortality is due to a reduction in death from the progression of heart failure 
    Output:
    