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 Trials of beta blockers in patients undergoing non-cardiac surgery have reported conflicting results . This r and omised controlled trial , done in 190 hospitals in 23 countries , was design ed to investigate the effects of perioperative beta blockers . METHODS We r and omly assigned 8351 patients with , or at risk of , atherosclerotic disease who were undergoing non-cardiac surgery to receive extended-release metoprolol succinate ( n=4174 ) or placebo ( n=4177 ) , by a computerised r and omisation phone service . Study treatment was started 2 - 4 h before surgery and continued for 30 days . Patients , health-care providers , data collectors , and outcome adjudicators were masked to treatment allocation . The primary endpoint was a composite of cardiovascular death , non-fatal myocardial infa rct ion , and non-fatal cardiac arrest . Analyses were by intention to treat . This trial is registered with Clinical Trials.gov , number NCT00182039 . FINDINGS All 8351 patients were included in analyses ; 8331 ( 99.8 % ) patients completed the 30-day follow-up . Fewer patients in the metoprolol group than in the placebo group reached the primary endpoint ( 244 [ 5.8 % ] patients in the metoprolol group vs 290 [ 6.9 % ] in the placebo group ; hazard ratio 0.84 , 95 % CI 0.70 - 0.99 ; p=0.0399 ) . Fewer patients in the metoprolol group than in the placebo group had a myocardial infa rct ion ( 176 [ 4.2 % ] vs 239 [ 5.7 % ] patients ; 0.73 , 0.60 - 0.89 ; p=0.0017 ) . However , there were more deaths in the metoprolol group than in the placebo group ( 129 [ 3.1 % ] vs 97 [ 2.3 % ] patients ; 1.33 , 1.03 - 1.74 ; p=0.0317 ) . More patients in the metoprolol group than in the placebo group had a stroke ( 41 [ 1.0 % ] vs 19 [ 0.5 % ] patients ; 2.17 , 1.26 - 3.74 ; p=0.0053 ) . INTERPRETATION Our results highlight the risk in assuming a perioperative beta-blocker regimen has benefit without substantial harm , and the importance and need for large r and omised trials in the perioperative setting . Patients are unlikely to accept the risks associated with perioperative extended-release metoprolol Objective —To get a better insight into the role of hemostasis in coronary artery disease ( CAD ) , we assessed the impact of von Willebr and factor ( vWF ) , fibrinogen , thrombin-antithrombin ( TAT ) complexes , D-dimers , and plasmin-antiplasmin ( PAP ) complexes on the risk of cardiovascular event in a prospect i ve cohort of CAD patients . Methods and Results —The prospect i ve Atherogene cohort includes 1057 individuals with an angiographically proven coronary artery disease at baseline . After a median follow-up of 6.6 years , 135 individuals died from a cardiovascular cause and 97 had a nonfatal cardiovascular event . Higher levels of all 5 hemostatic markers at baseline were associated with an increased risk of cardiovascular death , but not of nonfatal event . Except for vWF , these associations remained significant after adjustment for conventional cardiovascular risk factors and C-reactive protein ( CRP ) levels ( P for trend according to increasing tertiles=0.20 , 0.011 , 0.026 , 0.019 , and 0.01 for vWF , fibrinogen , TAT , D-Dimer , and PAP , respectively ) . When including the 5 hemostatic markers in a stepwise Cox regression analysis where conventional risk factors and CRP were forced into the model , fibrinogen and D-dimers remained independently associated with the risk of cardiovascular death . Adjusted hazard ratios ( 95 % CI ) associated with one SD increase of fibrinogen and D-dimers were 1.27 ( 1.04 to 1.55 ) and 1.29 ( 1.09 to 1.53 ) , respectively . Conclusions —In patients with coronary artery disease , fibrinogen and D-dimer levels are independent predictors of subsequent cardiovascular death . Our data support a role of impaired coagulation/fibrinolysis process in the complications of coronary artery disease OBJECTIVES The purpose of this study was to assess the value of preoperative cardiac testing in intermediate-risk patients receiving beta-blocker therapy with tight heart rate ( HR ) control scheduled for major vascular surgery . BACKGROUND Treatment guidelines of the American College of Cardiology/American Heart Association recommend cardiac testing in these patients to identify subjects at increased risk . This policy delays surgery , even though test results might be redundant and beta-blockers with tight HR control provide sufficient myocardial protection . Furthermore , the benefit of revascularization in high-risk patients is ill-defined . METHODS All 1,476 screened patients were stratified into low-risk ( 0 risk factors ) , intermediate-risk ( 1 to 2 risk factors ) , and high-risk ( > or =3 risk factors ) . All patients received beta-blockers . The 770 intermediate-risk patients were r and omly assigned to cardiac stress-testing ( n = 386 ) or no testing . Test results influenced management . In patients with ischemia , physicians aim ed to control HR below the ischemic threshold . Those with extensive stress-induced ischemia were considered for revascularization . The primary end point was cardiac death or myocardial infa rct ion at 30-days after surgery . RESULTS Testing showed no ischemia in 287 patients ( 74 % ) ; limited ischemia in 65 patients ( 17 % ) , and extensive ischemia in 34 patients ( 8.8 % ) . Of 34 patients with extensive ischemia , revascularization before surgery was feasible in 12 patients ( 35 % ) . Patients assigned to no testing had similar incidence of the primary end point as those assigned to testing ( 1.8 % vs. 2.3 % ; odds ratio [ OR ] 0.78 ; 95 % confidence interval [ CI ] 0.28 to 2.1 ; p = 0.62 ) . The strategy of no testing brought surgery almost 3 weeks forward . Regardless of allocated strategy , patients with a HR < 65 beats/min had lower risk than the remaining patients ( 1.3 % vs. 5.2 % ; OR 0.24 ; 95 % CI 0.09 to 0.66 ; p = 0.003 ) . CONCLUSIONS Cardiac testing can safely be omitted in intermediate-risk patients , provided that beta-blockers aim ing at tight HR control are prescribed Background — Few studies have examined whether hemostatic markers contribute to risk of coronary disease and ischemic stroke independently of conventional risk factors . This study examines 11 hemostatic markers that reflect different aspects of the coagulation process to determine which have prognostic value after accounting for conventional risk factors . Methods and Results — A total of 2398 men aged 49 to 65 years were examined in 1984 to 1988 , and the majority gave a fasting blood sample for assay of lipids and hemostatic markers . Men were followed up for a median of 13 years , and cardiovascular disease ( CVD ) events were recorded . There were 486 CVD events in total , 353 with prospect i ve coronary disease and 133 with prospect i ve ischemic stroke . On univariable analysis , fibrinogen , low activated protein C ratio , D-dimer , tissue plasminogen activator ( tPA ) , and plasminogen activator inhibitor-1 ( PAI-1 ) were associated significantly with risk of CVD . On multivariable analyses with conventional risk factors forced into the proportional hazards model , fibrinogen , D-dimer , and PAI-1 were significantly associated with risk of CVD , whereas factor VIIc showed an inverse association ( P=0.001 ) . In a model that contained the conventional risk factors , the hazard ratio for subsequent CVD in the top third of the distribution of predicted risk relative to the bottom third was 2.7 for subjects without preexisting CVD . This ratio increased to 3.7 for the model that also contained the 4 hemostatic factors . Conclusions — Fibrinogen , D-dimer , PAI-1 activity , and factor VIIc each has potential to increase the prediction of coronary disease/ischemic stroke in middle-aged men , in addition to conventional risk factors Background : Perioperative metoprolol increases  postoperative stroke .  Animal studies indicate that the mechanism may be related to attenuated & bgr;2-adrenoreceptor-mediated cerebral vasodilatation . The authors therefore conducted a cohort to study whether the highly & bgr;1-specific & bgr;-blocker ( bisoprolol ) was associated with a reduced risk of postoperative stroke compared with less selective & bgr;-blockers ( metoprolol or atenolol ) . Methods : The authors conducted a single-center study on 44,092 consecutive patients with age 50 yr or more having noncardiac , nonneurologic surgery . The primary outcome was stroke within 7 days of surgery . The secondary outcome was a composite of all-cause mortality , postoperative myocardial injury , and stroke . A propensity score-matched cohort was created to assess the independent association between bisoprolol and less & bgr;1-selective agents metoprolol or atenolol . A secondary analysis using logistic regression , based on previously identified confounders , also compared selective & bgr;1-antagonism . Results : Twenty-four percent ( 10,756 ) of patients were exposed to in-hospital & bgr;-blockers . A total of 88 patients ( 0.2 % ) suffered a stroke within 7 days of surgery . The matched cohort consisted of 2,462 patients , and the pairs were well matched for all variables . Bisoprolol was associated with fewer postoperative strokes than the less selective agents ( odds ratio = 0.20 ; 95 % CI , 0.04–0.91 ) . Multivariable risk-adjustment in the & bgr;-blockers-exposed patients comparing bisoprolol with the less selective agents was associated with a similarly reduced stroke rate . Conclusions : The use of metoprolol and atenolol is associated with increased risks of postoperative stroke , compared with bisoprolol . These findings warrant confirmation in a pragmatic r and omized trial AIM To assess the long-term cardioprotective effect of bisoprolol in a r and omized high-risk population after successful major vascular surgery . High-risk patients were defined by the presence of one or more cardiac risk factor(s ) and a dobutamine echocardiography test positive for ischaemia . METHODS 1351 patients were screened prior to surgery , 846 patients had one or more risk factor(s ) , and 173 of these patients also had ischaemia during dobutamine echocardiography . One hundred and twelve patients could be r and omized for additional bisoprolol therapy or st and ard care . Eleven patients died in the peri-operative period ( up to 1 month after surgery ) . R and omized patients continued bisoprolol or st and ard care after surgery . During follow-up of 101 survivors ( median 22 months , range 11 - 30 ) cardiac death or myocardial infa rct ion was noted . No patient was lost during follow-up . Results The incidence of cardiac events during follow-up in the bisoprolol group was 12 % vs 32 % in the st and ard care group ( P=0.025 ) . Cardiac death occurred in 15 patients , nine patients in the st and ard care and in six in the bisoprolol group ; myocardial infa rct ion occurred in six patients , five in the st and ard care and one in the bisoprolol group . The odds ratio for cardiac death or myocardial infa rct ion after surgery in high-risk patients with additional bisoprolol therapy was 0.30 ( 0.11 - 0.83 ) . CONCLUSIONS Bisoprolol significantly reduced long-term cardiac death and myocardial infa rct ion in high-risk patients after successful major cardiac vascular surgery Objective : This study was design ed to investigate whether patients with stable coronary artery disease ( CAD ) receiving chronic statin treatment who are undergoing noncardiac emergency surgery benefit from acute atorvastatin reload . Methods : A total of 500 patients with stable CAD and regular administration of statin before noncardiac emergency surgery were r and omized to atorvastatin reload ( n = 250 ) or placebo ( n = 250 ) . All patients received atorvastatin treatment thereafter . The primary end point was a 30-day incidence of major adverse cardiac events ( MACE ) . Secondary end points were the incidence of atrial fibrillation ( AF ) during hospitalization and length of hospital stay . Results : The primary end point occurred in 2.4 % of patients treated with atorvastatin reload and in 8 % in the placebo arm ( p = 0.0088 ) . The incidence of AF during hospitalization was 6.8 % in patients treated with atorvastatin reload and 17 % in the placebo arm ( p = 0.0003 ) . Compared with the placebo arm , the atorvastatin reload arm shortened the length 
    Output:
    
agent
Due to the limited number of included trials , there is insufficient evidence to draw any conclusions about the effectiveness of cardiovascular prophylaxis in reducing mortality and cardiovascular events in people with AAA .
***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 Trials of beta blockers in patients undergoing non-cardiac surgery have reported conflicting results . This r and omised controlled trial , done in 190 hospitals in 23 countries , was design ed to investigate the effects of perioperative beta blockers . METHODS We r and omly assigned 8351 patients with , or at risk of , atherosclerotic disease who were undergoing non-cardiac surgery to receive extended-release metoprolol succinate ( n=4174 ) or placebo ( n=4177 ) , by a computerised r and omisation phone service . Study treatment was started 2 - 4 h before surgery and continued for 30 days . Patients , health-care providers , data collectors , and outcome adjudicators were masked to treatment allocation . The primary endpoint was a composite of cardiovascular death , non-fatal myocardial infa rct ion , and non-fatal cardiac arrest . Analyses were by intention to treat . This trial is registered with Clinical Trials.gov , number NCT00182039 . FINDINGS All 8351 patients were included in analyses ; 8331 ( 99.8 % ) patients completed the 30-day follow-up . Fewer patients in the metoprolol group than in the placebo group reached the primary endpoint ( 244 [ 5.8 % ] patients in the metoprolol group vs 290 [ 6.9 % ] in the placebo group ; hazard ratio 0.84 , 95 % CI 0.70 - 0.99 ; p=0.0399 ) . Fewer patients in the metoprolol group than in the placebo group had a myocardial infa rct ion ( 176 [ 4.2 % ] vs 239 [ 5.7 % ] patients ; 0.73 , 0.60 - 0.89 ; p=0.0017 ) . However , there were more deaths in the metoprolol group than in the placebo group ( 129 [ 3.1 % ] vs 97 [ 2.3 % ] patients ; 1.33 , 1.03 - 1.74 ; p=0.0317 ) . More patients in the metoprolol group than in the placebo group had a stroke ( 41 [ 1.0 % ] vs 19 [ 0.5 % ] patients ; 2.17 , 1.26 - 3.74 ; p=0.0053 ) . INTERPRETATION Our results highlight the risk in assuming a perioperative beta-blocker regimen has benefit without substantial harm , and the importance and need for large r and omised trials in the perioperative setting . Patients are unlikely to accept the risks associated with perioperative extended-release metoprolol Objective —To get a better insight into the role of hemostasis in coronary artery disease ( CAD ) , we assessed the impact of von Willebr and factor ( vWF ) , fibrinogen , thrombin-antithrombin ( TAT ) complexes , D-dimers , and plasmin-antiplasmin ( PAP ) complexes on the risk of cardiovascular event in a prospect i ve cohort of CAD patients . Methods and Results —The prospect i ve Atherogene cohort includes 1057 individuals with an angiographically proven coronary artery disease at baseline . After a median follow-up of 6.6 years , 135 individuals died from a cardiovascular cause and 97 had a nonfatal cardiovascular event . Higher levels of all 5 hemostatic markers at baseline were associated with an increased risk of cardiovascular death , but not of nonfatal event . Except for vWF , these associations remained significant after adjustment for conventional cardiovascular risk factors and C-reactive protein ( CRP ) levels ( P for trend according to increasing tertiles=0.20 , 0.011 , 0.026 , 0.019 , and 0.01 for vWF , fibrinogen , TAT , D-Dimer , and PAP , respectively ) . When including the 5 hemostatic markers in a stepwise Cox regression analysis where conventional risk factors and CRP were forced into the model , fibrinogen and D-dimers remained independently associated with the risk of cardiovascular death . Adjusted hazard ratios ( 95 % CI ) associated with one SD increase of fibrinogen and D-dimers were 1.27 ( 1.04 to 1.55 ) and 1.29 ( 1.09 to 1.53 ) , respectively . Conclusions —In patients with coronary artery disease , fibrinogen and D-dimer levels are independent predictors of subsequent cardiovascular death . Our data support a role of impaired coagulation/fibrinolysis process in the complications of coronary artery disease OBJECTIVES The purpose of this study was to assess the value of preoperative cardiac testing in intermediate-risk patients receiving beta-blocker therapy with tight heart rate ( HR ) control scheduled for major vascular surgery . BACKGROUND Treatment guidelines of the American College of Cardiology/American Heart Association recommend cardiac testing in these patients to identify subjects at increased risk . This policy delays surgery , even though test results might be redundant and beta-blockers with tight HR control provide sufficient myocardial protection . Furthermore , the benefit of revascularization in high-risk patients is ill-defined . METHODS All 1,476 screened patients were stratified into low-risk ( 0 risk factors ) , intermediate-risk ( 1 to 2 risk factors ) , and high-risk ( > or =3 risk factors ) . All patients received beta-blockers . The 770 intermediate-risk patients were r and omly assigned to cardiac stress-testing ( n = 386 ) or no testing . Test results influenced management . In patients with ischemia , physicians aim ed to control HR below the ischemic threshold . Those with extensive stress-induced ischemia were considered for revascularization . The primary end point was cardiac death or myocardial infa rct ion at 30-days after surgery . RESULTS Testing showed no ischemia in 287 patients ( 74 % ) ; limited ischemia in 65 patients ( 17 % ) , and extensive ischemia in 34 patients ( 8.8 % ) . Of 34 patients with extensive ischemia , revascularization before surgery was feasible in 12 patients ( 35 % ) . Patients assigned to no testing had similar incidence of the primary end point as those assigned to testing ( 1.8 % vs. 2.3 % ; odds ratio [ OR ] 0.78 ; 95 % confidence interval [ CI ] 0.28 to 2.1 ; p = 0.62 ) . The strategy of no testing brought surgery almost 3 weeks forward . Regardless of allocated strategy , patients with a HR < 65 beats/min had lower risk than the remaining patients ( 1.3 % vs. 5.2 % ; OR 0.24 ; 95 % CI 0.09 to 0.66 ; p = 0.003 ) . CONCLUSIONS Cardiac testing can safely be omitted in intermediate-risk patients , provided that beta-blockers aim ing at tight HR control are prescribed Background — Few studies have examined whether hemostatic markers contribute to risk of coronary disease and ischemic stroke independently of conventional risk factors . This study examines 11 hemostatic markers that reflect different aspects of the coagulation process to determine which have prognostic value after accounting for conventional risk factors . Methods and Results — A total of 2398 men aged 49 to 65 years were examined in 1984 to 1988 , and the majority gave a fasting blood sample for assay of lipids and hemostatic markers . Men were followed up for a median of 13 years , and cardiovascular disease ( CVD ) events were recorded . There were 486 CVD events in total , 353 with prospect i ve coronary disease and 133 with prospect i ve ischemic stroke . On univariable analysis , fibrinogen , low activated protein C ratio , D-dimer , tissue plasminogen activator ( tPA ) , and plasminogen activator inhibitor-1 ( PAI-1 ) were associated significantly with risk of CVD . On multivariable analyses with conventional risk factors forced into the proportional hazards model , fibrinogen , D-dimer , and PAI-1 were significantly associated with risk of CVD , whereas factor VIIc showed an inverse association ( P=0.001 ) . In a model that contained the conventional risk factors , the hazard ratio for subsequent CVD in the top third of the distribution of predicted risk relative to the bottom third was 2.7 for subjects without preexisting CVD . This ratio increased to 3.7 for the model that also contained the 4 hemostatic factors . Conclusions — Fibrinogen , D-dimer , PAI-1 activity , and factor VIIc each has potential to increase the prediction of coronary disease/ischemic stroke in middle-aged men , in addition to conventional risk factors Background : Perioperative metoprolol increases  postoperative stroke .  Animal studies indicate that the mechanism may be related to attenuated & bgr;2-adrenoreceptor-mediated cerebral vasodilatation . The authors therefore conducted a cohort to study whether the highly & bgr;1-specific & bgr;-blocker ( bisoprolol ) was associated with a reduced risk of postoperative stroke compared with less selective & bgr;-blockers ( metoprolol or atenolol ) . Methods : The authors conducted a single-center study on 44,092 consecutive patients with age 50 yr or more having noncardiac , nonneurologic surgery . The primary outcome was stroke within 7 days of surgery . The secondary outcome was a composite of all-cause mortality , postoperative myocardial injury , and stroke . A propensity score-matched cohort was created to assess the independent association between bisoprolol and less & bgr;1-selective agents metoprolol or atenolol . A secondary analysis using logistic regression , based on previously identified confounders , also compared selective & bgr;1-antagonism . Results : Twenty-four percent ( 10,756 ) of patients were exposed to in-hospital & bgr;-blockers . A total of 88 patients ( 0.2 % ) suffered a stroke within 7 days of surgery . The matched cohort consisted of 2,462 patients , and the pairs were well matched for all variables . Bisoprolol was associated with fewer postoperative strokes than the less selective agents ( odds ratio = 0.20 ; 95 % CI , 0.04–0.91 ) . Multivariable risk-adjustment in the & bgr;-blockers-exposed patients comparing bisoprolol with the less selective agents was associated with a similarly reduced stroke rate . Conclusions : The use of metoprolol and atenolol is associated with increased risks of postoperative stroke , compared with bisoprolol . These findings warrant confirmation in a pragmatic r and omized trial AIM To assess the long-term cardioprotective effect of bisoprolol in a r and omized high-risk population after successful major vascular surgery . High-risk patients were defined by the presence of one or more cardiac risk factor(s ) and a dobutamine echocardiography test positive for ischaemia . METHODS 1351 patients were screened prior to surgery , 846 patients had one or more risk factor(s ) , and 173 of these patients also had ischaemia during dobutamine echocardiography . One hundred and twelve patients could be r and omized for additional bisoprolol therapy or st and ard care . Eleven patients died in the peri-operative period ( up to 1 month after surgery ) . R and omized patients continued bisoprolol or st and ard care after surgery . During follow-up of 101 survivors ( median 22 months , range 11 - 30 ) cardiac death or myocardial infa rct ion was noted . No patient was lost during follow-up . Results The incidence of cardiac events during follow-up in the bisoprolol group was 12 % vs 32 % in the st and ard care group ( P=0.025 ) . Cardiac death occurred in 15 patients , nine patients in the st and ard care and in six in the bisoprolol group ; myocardial infa rct ion occurred in six patients , five in the st and ard care and one in the bisoprolol group . The odds ratio for cardiac death or myocardial infa rct ion after surgery in high-risk patients with additional bisoprolol therapy was 0.30 ( 0.11 - 0.83 ) . CONCLUSIONS Bisoprolol significantly reduced long-term cardiac death and myocardial infa rct ion in high-risk patients after successful major cardiac vascular surgery Objective : This study was design ed to investigate whether patients with stable coronary artery disease ( CAD ) receiving chronic statin treatment who are undergoing noncardiac emergency surgery benefit from acute atorvastatin reload . Methods : A total of 500 patients with stable CAD and regular administration of statin before noncardiac emergency surgery were r and omized to atorvastatin reload ( n = 250 ) or placebo ( n = 250 ) . All patients received atorvastatin treatment thereafter . The primary end point was a 30-day incidence of major adverse cardiac events ( MACE ) . Secondary end points were the incidence of atrial fibrillation ( AF ) during hospitalization and length of hospital stay . Results : The primary end point occurred in 2.4 % of patients treated with atorvastatin reload and in 8 % in the placebo arm ( p = 0.0088 ) . The incidence of AF during hospitalization was 6.8 % in patients treated with atorvastatin reload and 17 % in the placebo arm ( p = 0.0003 ) . Compared with the placebo arm , the atorvastatin reload arm shortened the length 
    Output:
    