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 —Inflammation promotes acute coronary syndromes and ensuing clinical complications . Although statins reduce inflammatory markers in asymptomatic adults or in patients with stable angina , the effect of statins on the markedly heightened inflammation in patients with acute coronary syndromes is unknown . Methods and Results —We measured C-reactive protein ( CRP ) , serum amyloid A ( SAA ) , and interleukin 6 ( IL-6 ) in 2402 subjects enrolled the Myocardial Ischemia Reduction with Aggressive Cholesterol Lowering ( MIRACL ) study . Subjects with unstable angina or non – Q-wave myocardial infa rct ion were r and omized to atorvastatin 80 mg/d or placebo within 24 to 96 hours of hospital admission and treated for 16 weeks . The effect of treatment on inflammatory markers was assessed by ANCOVA after adjustment for presenting syndrome , country , and initial level of marker . All 3 markers were markedly elevated at r and omization and declined over the 16 weeks in both treatment groups . Compared with placebo , atorvastatin significantly reduced CRP , −83 % ( 95 % CI , −84 % , −81 % ) versus −74 % ( 95 % CI , −75 % , −71 % ) ( P < 0.0001 ) and SAA , −80 % ( 95 % CI , −82 % , −78 % ) versus −77 % ( −79 % , −75 % ) ( P = 0.0006 ) but not IL-6 , −55 % ( 95 % CI , −57 % , −53 % ) versus −53 % ( 95 % CI , −55 % , −51 % ) ( P = 0.3 ) . Reductions in CRP and SAA were observed in patients with unstable angina and non – Q-wave myocardial infa rct ion , with initial LDL cholesterol < 3.2 or ≥3.2 mmol/L ( 125 mg/dL ) , age ≥65 or < 65 years , and in men and women . By 16 weeks , CRP was 34 % lower with atorvastatin than with placebo . Conclusions —High-dose atorvastatin potentiated the decline in inflammation in patients with acute coronary syndromes . This supports the value of early statin therapy in these patients CONTEXT Atrial fibrillation is a common , but potentially preventable , complication following coronary artery bypass graft ( CABG ) surgery . OBJECTIVES To assess the nature and consequences of atrial fibrillation after CABG surgery and to develop a comprehensive risk index that can better identify patients at risk for atrial fibrillation . DESIGN , SETTING , AND PARTICIPANTS Prospect i ve observational study of 4657 patients undergoing CABG surgery between November 1996 and June 2000 at 70 centers located within 17 countries , selected using a systematic sampling technique . From a derivation cohort of 3093 patients , associations between predictor variables and postoperative atrial fibrillation were identified to develop a risk model , which was assessed in a validation cohort of 1564 patients . MAIN OUTCOME MEASURE New-onset atrial fibrillation after CABG surgery . RESULTS A total of 1503 patients ( 32.3 % ) developed atrial fibrillation after CABG surgery . Postoperative atrial fibrillation was associated with subsequent greater re source use as well as with cognitive changes , renal dysfunction , and infection . Among patients in the derivation cohort , risk factors associated with atrial fibrillation were advanced age ( odds ratio [ OR ] for 10-year increase , 1.75 ; 95 % confidence interval [ CI ] , 1.59 - 1.93 ) ; history of atrial fibrillation ( OR , 2.11 ; 95 % CI , 1.57 - 2.85 ) or chronic obstructive pulmonary disease ( OR , 1.43 ; 95 % CI , 1.09 - 1.87 ) ; valve surgery ( OR , 1.74 ; 95 % CI , 1.31 - 2.32 ) ; and postoperative withdrawal of a beta-blocker ( OR , 1.91 ; 95 % CI , 1.52 - 2.40 ) or an angiotensin-converting enzyme ( ACE ) inhibitor ( OR 1.69 ; 95 % CI , 1.38 - 2.08 ) . Conversely , reduced risk was associated with postoperative administration of beta-blockers ( OR , 0.32 ; 95 % CI , 0.22 - 0.46 ) , ACE inhibitors ( OR , 0.62 ; 95 % CI , 0.48 - 0.79 ) , potassium supplementation ( OR , 0.53 ; 95 % CI , 0.42 - 0.68 ) , and nonsteroidal anti-inflammatory drugs ( OR , 0.49 ; 95 % CI , 0.40 - 0.60 ) . The result ing multivariable risk index had adequate discriminative power with an area under the receiver operating characteristic ( ROC ) curve of 0.77 in the validation sample . Forty-three percent ( 640/1503 ) of patients who had atrial fibrillation after CABG surgery experienced more than 1 episode of atrial fibrillation . Predictors of recurrent atrial fibrillation included older age , history of congestive heart failure , left ventricular hypertrophy , aortic atherosclerosis , bicaval venous cannulation , withdrawal of ACE inhibitor or beta-blocker therapy , and use of amiodarone or digoxin ( area under the ROC curve of 0.66 ) . Patients with recurrent atrial fibrillation had longer hospital stays and experienced greater infectious , renal , and neurological complications than those with a single episode . CONCLUSIONS We have developed and vali date d models predicting the occurrence of atrial fibrillation  after CABG surgery based on an analysis of a large multicenter international cohort . Our findings suggest that treatment with beta-blockers , ACE inhibitors , and /or nonsteroidal anti-inflammatory drugs may offer protection . Atrial fibrillation after CABG surgery is associated with important complications Background — Atrial fibrillation ( AF ) after cardiac surgery is associated with increased risk of complications , length of stay , and cost of care . Observational evidence suggests that patients who have undergone previous statin therapy have a lower incidence of postoperative AF . We tested this observation in a r and omized , controlled trial . Methods and Results — Two hundred patients undergoing elective cardiac surgery with cardiopulmonary bypass , without previous statin treatment or history of AF , were enrolled . Patients were r and omized to atorvastatin ( 40 mg/d , n=101 ) or placebo  ( n=99 ) starting 7 days before operation . The primary end point was incidence of postoperative AF ; secondary end points were length of stay , 30-day major adverse cardiac and cerebrovascular events , and postoperative C-reactive protein ( CRP ) variations . Atorvastatin significantly reduced the incidence of AF versus placebo ( 35 % versus 57 % , P=0.003 ) . Accordingly , length of stay was longer in the placebo versus atorvastatin arm ( 6.9±1.4 versus 6.3±1.2 days , P=0.001 ) . Peak CRP levels were lower in patients without AF ( P=0.01 ) , irrespective of r and omization assignment . Multivariable analysis showed that atorvastatin treatment conferred a 61 % reduction in risk of AF ( odds ratio 0.39 , 95 % confidence interval 0.18 to 0.85 , P=0.017 ) , whereas high postoperative CRP levels were associated with increased risk ( odds ratio 2.0 , 95 % confidence interval 1.2 to 7.0 , P=0.01 ) . The incidence of major adverse cardiac and cerebrovascular events at 30 days was similar in the 2 arms . Conclusions — Treatment with atorvastatin 40 mg/d , initiated 7 days before surgery , significantly reduces the incidence of postoperative AF after elective cardiac surgery with cardiopulmonary bypass and shortens hospital stay . These results may influence practice patterns with regard to adjuvant pharmacological therapy before cardiac surgery CONTEXT Patients experience the highest rate of death and recurrent ischemic events during the early period after an acute coronary syndrome , but it is not known whether early initiation of treatment with a statin can reduce the occurrence of these early events . OBJECTIVE To determine whether treatment with atorvastatin , 80 mg/d , initiated 24 to 96 hours after an acute coronary syndrome , reduces death and nonfatal ischemic events . DESIGN AND SETTING A r and omized , double-blind trial conducted from May 1997 to September 1999 , with follow-up through 16 weeks at 122 clinical centers in Europe , North America , South Africa , and Australasia . PATIENTS A total of 3086 adults aged 18 years or older with unstable angina or non-Q-wave acute myocardial infa rct ion . INTERVENTIONS Patients were stratified by center and r and omly assigned to receive treatment with atorvastatin ( 80 mg/d ) or matching placebo between 24 and 96 hours after hospital admission . MAIN OUTCOME MEASURES Primary end point event defined as death , nonfatal acute myocardial infa rct ion , cardiac arrest with resuscitation , or recurrent symptomatic myocardial ischemia with objective evidence and requiring emergency rehospitalization . RESULTS A primary end point event occurred in 228 patients ( 14.8 % ) in the atorvastatin group and 269 patients ( 17.4 % ) in the placebo group ( relative risk [ RR ] , 0.84 ; 95 % confidence interval [ CI ] , 0.70 - 1.00 ; P = .048 ) . There were no significant differences in risk of death , nonfatal myocardial infa rct ion , or cardiac arrest between the atorvastatin group and the placebo group , although the atorvastatin group had a lower risk of symptomatic ischemia with objective evidence and requiring emergency rehospitalization ( 6.2 % vs 8.4 % ; RR , 0.74 ; 95 % CI , 0.57 - 0.95 ; P = .02 ) . Likewise , there were no significant differences between the atorvastatin group and the placebo group in the incidence of secondary outcomes of coronary revascularization procedures , worsening heart failure , or worsening angina , although there were fewer strokes in the atorvastatin group than in the placebo group ( 12 vs 24 events ; P = .045 ) . In the atorvastatin group , mean low-density lipoprotein cholesterol level declined from 124 mg/dL ( 3.2 mmol/L ) to 72 mg/dL ( 1.9 mmol/L ) . Abnormal liver transaminases ( > 3 times upper limit of normal ) were more common in the atorvastatin group than in the placebo group ( 2.5 % vs 0.6 % ; P<.001 ) . CONCLUSION For patients with acute coronary syndrome , lipid-lowering therapy with atorvastatin , 80 mg/d , reduces recurrent ischemic events in the first 16 weeks , mostly recurrent symptomatic ischemia requiring rehospitalization BACKGROUND Previous prospect i ve outcome studies of statins have not provided any guidance on benefit-risk in patients with heart failure . AIM The primary objective is to determine whether rosuvastatin ( 10 mg ) reduces the combined endpoint of cardiovascular mortality , non-fatal myocardial infa rct ion or non-fatal stroke ( time to first event ) . The first secondary endpoint is all-cause mortality . METHODS CORONA is a r and omized , double-blind , placebo-controlled trial . Briefly , men and women , aged > or = 60 years with chronic symptomatic systolic heart failure of ischemic aetiology and ejection fraction < or = 0.40 ( NYHA class III and IV ) or < or = 0.35 ( NYHA class II ) were eligible if they were not using or in need of cholesterol lowering drugs .  RESULTS Mean age was 73 years ( n=5016 ; 24 % women ) , with 37 % in NYHA II and 62 % in NYHA III , ejection fraction 0.31 , total cholesterol 5.2 mmol/L. Sixty percent have a history of myocardial infa rct ion , 63 % hypertension , and 30 % diabetes . Patients are well treated for heart failure with 90 % on loop or thiazide diuretics , 42 % aldosterone antagonists , 91 % ACE inhibitor or AT-I blocker , 75 % beta-blockers , and 32 % digitalis . CONCLUSION CORONA is important for three main reasons : ( 1 ) A positive result is very important because of the high risk of the population studied , the increasing prevalence of elderly patients with chronic symptomatic systolic heart failure in our society , and the health economic issues involved . ( 2 ) If negative , new mechanistic questions about heart failure have to be raised . (  
    Output:
    
agent
Use of statins was significantly associated with a decreased risk of incidence or recurrence of AF in patients in sinus rhythm with a history of previous AF or undergoing cardiac surgery or after acute coronary syndrome
***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 —Inflammation promotes acute coronary syndromes and ensuing clinical complications . Although statins reduce inflammatory markers in asymptomatic adults or in patients with stable angina , the effect of statins on the markedly heightened inflammation in patients with acute coronary syndromes is unknown . Methods and Results —We measured C-reactive protein ( CRP ) , serum amyloid A ( SAA ) , and interleukin 6 ( IL-6 ) in 2402 subjects enrolled the Myocardial Ischemia Reduction with Aggressive Cholesterol Lowering ( MIRACL ) study . Subjects with unstable angina or non – Q-wave myocardial infa rct ion were r and omized to atorvastatin 80 mg/d or placebo within 24 to 96 hours of hospital admission and treated for 16 weeks . The effect of treatment on inflammatory markers was assessed by ANCOVA after adjustment for presenting syndrome , country , and initial level of marker . All 3 markers were markedly elevated at r and omization and declined over the 16 weeks in both treatment groups . Compared with placebo , atorvastatin significantly reduced CRP , −83 % ( 95 % CI , −84 % , −81 % ) versus −74 % ( 95 % CI , −75 % , −71 % ) ( P < 0.0001 ) and SAA , −80 % ( 95 % CI , −82 % , −78 % ) versus −77 % ( −79 % , −75 % ) ( P = 0.0006 ) but not IL-6 , −55 % ( 95 % CI , −57 % , −53 % ) versus −53 % ( 95 % CI , −55 % , −51 % ) ( P = 0.3 ) . Reductions in CRP and SAA were observed in patients with unstable angina and non – Q-wave myocardial infa rct ion , with initial LDL cholesterol < 3.2 or ≥3.2 mmol/L ( 125 mg/dL ) , age ≥65 or < 65 years , and in men and women . By 16 weeks , CRP was 34 % lower with atorvastatin than with placebo . Conclusions —High-dose atorvastatin potentiated the decline in inflammation in patients with acute coronary syndromes . This supports the value of early statin therapy in these patients CONTEXT Atrial fibrillation is a common , but potentially preventable , complication following coronary artery bypass graft ( CABG ) surgery . OBJECTIVES To assess the nature and consequences of atrial fibrillation after CABG surgery and to develop a comprehensive risk index that can better identify patients at risk for atrial fibrillation . DESIGN , SETTING , AND PARTICIPANTS Prospect i ve observational study of 4657 patients undergoing CABG surgery between November 1996 and June 2000 at 70 centers located within 17 countries , selected using a systematic sampling technique . From a derivation cohort of 3093 patients , associations between predictor variables and postoperative atrial fibrillation were identified to develop a risk model , which was assessed in a validation cohort of 1564 patients . MAIN OUTCOME MEASURE New-onset atrial fibrillation after CABG surgery . RESULTS A total of 1503 patients ( 32.3 % ) developed atrial fibrillation after CABG surgery . Postoperative atrial fibrillation was associated with subsequent greater re source use as well as with cognitive changes , renal dysfunction , and infection . Among patients in the derivation cohort , risk factors associated with atrial fibrillation were advanced age ( odds ratio [ OR ] for 10-year increase , 1.75 ; 95 % confidence interval [ CI ] , 1.59 - 1.93 ) ; history of atrial fibrillation ( OR , 2.11 ; 95 % CI , 1.57 - 2.85 ) or chronic obstructive pulmonary disease ( OR , 1.43 ; 95 % CI , 1.09 - 1.87 ) ; valve surgery ( OR , 1.74 ; 95 % CI , 1.31 - 2.32 ) ; and postoperative withdrawal of a beta-blocker ( OR , 1.91 ; 95 % CI , 1.52 - 2.40 ) or an angiotensin-converting enzyme ( ACE ) inhibitor ( OR 1.69 ; 95 % CI , 1.38 - 2.08 ) . Conversely , reduced risk was associated with postoperative administration of beta-blockers ( OR , 0.32 ; 95 % CI , 0.22 - 0.46 ) , ACE inhibitors ( OR , 0.62 ; 95 % CI , 0.48 - 0.79 ) , potassium supplementation ( OR , 0.53 ; 95 % CI , 0.42 - 0.68 ) , and nonsteroidal anti-inflammatory drugs ( OR , 0.49 ; 95 % CI , 0.40 - 0.60 ) . The result ing multivariable risk index had adequate discriminative power with an area under the receiver operating characteristic ( ROC ) curve of 0.77 in the validation sample . Forty-three percent ( 640/1503 ) of patients who had atrial fibrillation after CABG surgery experienced more than 1 episode of atrial fibrillation . Predictors of recurrent atrial fibrillation included older age , history of congestive heart failure , left ventricular hypertrophy , aortic atherosclerosis , bicaval venous cannulation , withdrawal of ACE inhibitor or beta-blocker therapy , and use of amiodarone or digoxin ( area under the ROC curve of 0.66 ) . Patients with recurrent atrial fibrillation had longer hospital stays and experienced greater infectious , renal , and neurological complications than those with a single episode . CONCLUSIONS We have developed and vali date d models predicting the occurrence of atrial fibrillation  after CABG surgery based on an analysis of a large multicenter international cohort . Our findings suggest that treatment with beta-blockers , ACE inhibitors , and /or nonsteroidal anti-inflammatory drugs may offer protection . Atrial fibrillation after CABG surgery is associated with important complications Background — Atrial fibrillation ( AF ) after cardiac surgery is associated with increased risk of complications , length of stay , and cost of care . Observational evidence suggests that patients who have undergone previous statin therapy have a lower incidence of postoperative AF . We tested this observation in a r and omized , controlled trial . Methods and Results — Two hundred patients undergoing elective cardiac surgery with cardiopulmonary bypass , without previous statin treatment or history of AF , were enrolled . Patients were r and omized to atorvastatin ( 40 mg/d , n=101 ) or placebo  ( n=99 ) starting 7 days before operation . The primary end point was incidence of postoperative AF ; secondary end points were length of stay , 30-day major adverse cardiac and cerebrovascular events , and postoperative C-reactive protein ( CRP ) variations . Atorvastatin significantly reduced the incidence of AF versus placebo ( 35 % versus 57 % , P=0.003 ) . Accordingly , length of stay was longer in the placebo versus atorvastatin arm ( 6.9±1.4 versus 6.3±1.2 days , P=0.001 ) . Peak CRP levels were lower in patients without AF ( P=0.01 ) , irrespective of r and omization assignment . Multivariable analysis showed that atorvastatin treatment conferred a 61 % reduction in risk of AF ( odds ratio 0.39 , 95 % confidence interval 0.18 to 0.85 , P=0.017 ) , whereas high postoperative CRP levels were associated with increased risk ( odds ratio 2.0 , 95 % confidence interval 1.2 to 7.0 , P=0.01 ) . The incidence of major adverse cardiac and cerebrovascular events at 30 days was similar in the 2 arms . Conclusions — Treatment with atorvastatin 40 mg/d , initiated 7 days before surgery , significantly reduces the incidence of postoperative AF after elective cardiac surgery with cardiopulmonary bypass and shortens hospital stay . These results may influence practice patterns with regard to adjuvant pharmacological therapy before cardiac surgery CONTEXT Patients experience the highest rate of death and recurrent ischemic events during the early period after an acute coronary syndrome , but it is not known whether early initiation of treatment with a statin can reduce the occurrence of these early events . OBJECTIVE To determine whether treatment with atorvastatin , 80 mg/d , initiated 24 to 96 hours after an acute coronary syndrome , reduces death and nonfatal ischemic events . DESIGN AND SETTING A r and omized , double-blind trial conducted from May 1997 to September 1999 , with follow-up through 16 weeks at 122 clinical centers in Europe , North America , South Africa , and Australasia . PATIENTS A total of 3086 adults aged 18 years or older with unstable angina or non-Q-wave acute myocardial infa rct ion . INTERVENTIONS Patients were stratified by center and r and omly assigned to receive treatment with atorvastatin ( 80 mg/d ) or matching placebo between 24 and 96 hours after hospital admission . MAIN OUTCOME MEASURES Primary end point event defined as death , nonfatal acute myocardial infa rct ion , cardiac arrest with resuscitation , or recurrent symptomatic myocardial ischemia with objective evidence and requiring emergency rehospitalization . RESULTS A primary end point event occurred in 228 patients ( 14.8 % ) in the atorvastatin group and 269 patients ( 17.4 % ) in the placebo group ( relative risk [ RR ] , 0.84 ; 95 % confidence interval [ CI ] , 0.70 - 1.00 ; P = .048 ) . There were no significant differences in risk of death , nonfatal myocardial infa rct ion , or cardiac arrest between the atorvastatin group and the placebo group , although the atorvastatin group had a lower risk of symptomatic ischemia with objective evidence and requiring emergency rehospitalization ( 6.2 % vs 8.4 % ; RR , 0.74 ; 95 % CI , 0.57 - 0.95 ; P = .02 ) . Likewise , there were no significant differences between the atorvastatin group and the placebo group in the incidence of secondary outcomes of coronary revascularization procedures , worsening heart failure , or worsening angina , although there were fewer strokes in the atorvastatin group than in the placebo group ( 12 vs 24 events ; P = .045 ) . In the atorvastatin group , mean low-density lipoprotein cholesterol level declined from 124 mg/dL ( 3.2 mmol/L ) to 72 mg/dL ( 1.9 mmol/L ) . Abnormal liver transaminases ( > 3 times upper limit of normal ) were more common in the atorvastatin group than in the placebo group ( 2.5 % vs 0.6 % ; P<.001 ) . CONCLUSION For patients with acute coronary syndrome , lipid-lowering therapy with atorvastatin , 80 mg/d , reduces recurrent ischemic events in the first 16 weeks , mostly recurrent symptomatic ischemia requiring rehospitalization BACKGROUND Previous prospect i ve outcome studies of statins have not provided any guidance on benefit-risk in patients with heart failure . AIM The primary objective is to determine whether rosuvastatin ( 10 mg ) reduces the combined endpoint of cardiovascular mortality , non-fatal myocardial infa rct ion or non-fatal stroke ( time to first event ) . The first secondary endpoint is all-cause mortality . METHODS CORONA is a r and omized , double-blind , placebo-controlled trial . Briefly , men and women , aged > or = 60 years with chronic symptomatic systolic heart failure of ischemic aetiology and ejection fraction < or = 0.40 ( NYHA class III and IV ) or < or = 0.35 ( NYHA class II ) were eligible if they were not using or in need of cholesterol lowering drugs .  RESULTS Mean age was 73 years ( n=5016 ; 24 % women ) , with 37 % in NYHA II and 62 % in NYHA III , ejection fraction 0.31 , total cholesterol 5.2 mmol/L. Sixty percent have a history of myocardial infa rct ion , 63 % hypertension , and 30 % diabetes . Patients are well treated for heart failure with 90 % on loop or thiazide diuretics , 42 % aldosterone antagonists , 91 % ACE inhibitor or AT-I blocker , 75 % beta-blockers , and 32 % digitalis . CONCLUSION CORONA is important for three main reasons : ( 1 ) A positive result is very important because of the high risk of the population studied , the increasing prevalence of elderly patients with chronic symptomatic systolic heart failure in our society , and the health economic issues involved . ( 2 ) If negative , new mechanistic questions about heart failure have to be raised . (  
    Output:
    