***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 The long-term effects of carvedilol on muscle sympathetic nerve activity ( MSNA ) and muscle blood flow at rest and exercise in patients with chronic heart failure ( CHF ) remain unknown . METHODS AND RESULTS Twenty-six patients ( New York Heart Association class II-III ) were r and omized to carvedilol or placebo .  Blood pressure , heart rate , MSNA , and forearm vascular resistance ( FVR ) at rest and during isometric forearm exercise ( 10 % and 30 % maximal voluntary contraction ) were assessed before and after 6 months . Seven patients did not complete the study . Paired data were obtained in 19 ( carvedilol 12 , placebo 7 ) . Carvedilol significantly decreased MSNA levels and heart rate at rest ( -13 + /- 2 versus 3 + /- 8 bursts/min , P = .0001 and -16 + /- 3 vs -4 + /- 6 bpm , P = .05 , respectively ) and peak exercise ( 30 % = -20 + /- 5 versus -3 + /- 7 bursts/min , P = 0.05 and -19 + /- 4 versus -4 + /- 6 bpm , P = 0.03 , respectively ) when compared with placebo . Carvedilol did not change a magnitude of response of MSNA and heart rate during exercise ( -10 + /- 3 versus -7 + /- 2 bursts/min , P = 0.7 and 11 + /- 3 versus 6 + /- 1 , P = .6 , respectively ) . FVR was unchanged by carvedilol . When MSNA was quantified by burst incidence , the strength of reduction in MSNA was attenuated but still greater than placebo . CONCLUSIONS Carvedilol reduces MSNA in patients with CHF .  Carvedilol does not reduce FVR at rest or during isometric exercise Background —Chronic heart failure is associated with inflammation and neurohormonal imbalance . The 3-hydroxy-3-methylglutaryl-CoA ( HMG-CoA ) reductase inhibitors , or statins , exert anti-inflammatory and vascular protective effects . We hypothesized that short-term statin therapy may have beneficial effects in patients with nonischemic heart failure . Methods and Results —Sixty-three patients with symptomatic , nonischemic , dilated cardiomyopathy were r and omly divided into 2 groups . One group received simvastatin ( n=24 ) , and the other group received placebo ( n=27 ) . The initial dose of simvastatin was 5 mg/d , which was increased to 10 mg/d after 4 weeks . After 14 weeks , patients receiving simvastatin exhibited a modest reduction in serum cholesterol level compared with patients receiving placebo ( 130±13 versus 148±18 , P < 0.05 ) . Patients treated with simvastatin had a lower New York Heart Association functional class compared with patients receiving placebo ( 2.04±0.06 versus 2.32±0.05 , P < 0.01 ) . This corresponded to improved left ventricular ejection fraction in the simvastatin group ( 34±3 to 41±4 % , P < 0.05 ) but not in the placebo group . Furthermore , plasma concentrations of tumor necrosis factor-&agr ; , interleukin-6 , and brain natriuretic peptide were significantly lower in the simvastatin group compared with the placebo group . Conclusions —Short-term statin therapy  improves cardiac function , neurohormonal imbalance , and symptoms associated with idiopathic dilated cardiomyopathy . These findings suggest that statins may have therapeutic benefits in patients with heart failure irrespective of serum cholesterol levels or atherosclerotic heart disease Objective To do an indirect comparison analysis of apixaban against dabigatran etexilate ( 2 doses ) and rivaroxaban ( 1 dose ) , as well as of rivaroxaban against dabigatranetexilate ( 2 doses ) , for their relative efficacy and safety against each other , with particular focus on the secondary prevention population for stroke prevention in atrial fibrillation . A secondary objective was to do the same analysis in the primary prevention cohort . Design Indirect treatment comparisons of phase III clinical trials of stroke prevention in atrial fibrillation , with a focus on the secondary prevention cohorts . A secondary analysis was done on the primary prevention cohort . Data sources Medline and Central ( up to June 2012 ) , clinical trials registers , conference proceedings , and websites of regulatory agencies . Study selection R and omised controlled trials of rivaroxaban , dabigatran , or apixaban compared with warfarin for stroke prevention in atrial fibrillation . Results In the secondary prevention ( previous stroke ) subgroup , when apixaban was compared with dabigatran ( 110 mg and 150 mg twice daily ) for efficacy and safety endpoints , the only significant difference seen was less myocardial infa rct ion ( hazard ratio 0.39 , 95 % confidence interval 0.16 to 0.95 ) with apixaban compared with dabigatran 150 mg twice daily . No significant differences were seen in efficacy and most safety endpoints between apixaban or dabigatran 150 mg twice daily versus rivaroxaban . Less haemorrhagic stroke ( hazard ratio 0.15 , 0.03 to 0.66 ) , vascular death ( 0.64 , 0.42 to 0.99 ) , major bleeding ( 0.68 , 0.47 to 0.99 ) , and intracranial bleeding ( 0.27 , 0.10 to 0.73 ) were seen with dabigatran 110 mg twice daily versus rivaroxaban . In the primary prevention ( no previous stroke ) subgroup , apixaban was superior to dabigatran 110 mg twice daily for disabling or fatal stroke ( hazard ratio 0.59 , 0.36 to 0.97 ) . Compared with dabigatran 150 mg twice daily , apixaban was associated with more stroke ( hazard ratio 1.45 , 1.01 to 2.08 ) and with less major bleeding ( 0.75 , 0.60 to 0.94 ) , gastrointestinal bleeding ( 0.61 , 0.42 to 0.89 ) , and other location bleeding ( 0.74 , 0.58 to 0.94 ) . Compared with rivaroxaban , dabigatran 110 mg twice daily was associated with more myocardial infa rct ion events . No significant differences were seen for the main efficacy and safety endpoints between dabigatran 150 mg twice daily and rivaroxaban , or in efficacy endpoints between apixaban and rivaroxaban . Apixaban was associated with less major bleeding ( hazard ratio 0.61 , 0.48 to 0.78 ) than rivaroxaban . Conclusions For secondary prevention , apixaban , rivaroxaban , and dabigatran had broadly similar efficacy for the main endpoints , although the endpoints of haemorrhagic stroke , vascular death , major bleeding , and intracranial bleeding were less common with dabigatran 110 mg twice daily than with rivaroxaban . For primary prevention , the three drugs showed some differences in relation to efficacy and bleeding . These results are hypothesis generating and should be confirmed in a head to head r and omised trial This retrospective , nonr and omized analysis evaluated the effect of initiating statin or beta-blocker treatment early in the course of heart failure developed during acute myocardial infa rct ion compared with the effect of neither or both treatments . Early initiation of statins or beta blockers alone was associated with improved event-free survival , and the benefits of the combined treatment were additive BACKGROUND Statins have pleiotropic effects , such as improvement in endothelial function and antiinflammatory , antiproliferative , and antioxidative effects , that should be beneficial for patients with chronic heart failure ( CHF ) . The aim of this study was to investigate the long-term effect of statins on neurohumoral activation and cardiac function in patients with CHF . METHODS We enrolled 38 out patients with mild to moderate CHF and radionuclide left ventricular ejection fraction ( LVEF ) < 40 % . These patients were r and omly assigned to receive atorvastatin ( 10 mg/d ) or conventional treatment for heart failure and were prospect ively followed up for at least 3 years . At entry , we measured plasma concentrations of brain natriuretic peptides ( BNPs ) and left ventricular end-diastolic dimension and LVEF by echocardiography ; thereafter , these measurements were repeated at least every 6 months . The primary end point was defined as the improvement in cardiac function and BNP . RESULTS There were no significant differences in age , sex , New York Heart Association class , left ventricular end-diastolic dimension , LVEF , and serum cholesterol level at entry between patients with ( n = 19 ) and without atorvastatin ( control , n = 19 ) . After a follow-up period of 31 + /- 14 months , BNP ( median [ 25th , 75th percentile ] ) significantly decreased in the atorvastatin group ( 84 [ 36 , 186 ] to 55 [ 37 , 91 ] pg/mL , P = .02 ) but not in the control group . Left ventricular end-diastolic dimension significantly decreased ( 67.1 [ 59.9 , 70.8 ] to 61.1 [ 58 , 63.9 ] mm , P = .02 ) , and LVEF also significantly increased in the atorvastatin group ( 33.3 % + /- 7.4 % to 39.1 % + /- 12.1 % , P = .01 ) but not in the control group . CONCLUSION Long-term atorvastatin therapy decreases neurohumoral activation and improves cardiac function in patients with mild to moderate CHF Background — Small studies suggest that statins may improve mortality in patients with heart failure ( HF ) . Whether these results are generalizable to a broader group of patients with HF remains unclear . Our objective was to evaluate the association between statin use and survival among a national sample of elderly patients hospitalized with HF . Methods and Results — A nationwide sample of 61 939 eligible Medicare beneficiaries ≥65 years of age who were hospitalized with a primary discharge diagnosis of HF between April 1998 and March 1999 or July 2000 and June 2001 was evaluated . The analysis was restricted to patients with no contraindications to statins ( n=54 960 ) . Of these patients , only 16.7 % received statins on discharge . Older patients were less likely to receive a statin  at discharge . Patients with hyperlipidemia and those cared for by a cardiologist or cared for in a teaching hospital were more likely to receive a statin at discharge . In a Cox proportional hazards model that took into account demographic , clinical characteristics , treatments , physician specialty , and hospital characteristics , discharge statin therapy was associated with significant improvements in 1- and 3-year mortality ( hazard ratio , 0.80 ; 95 % CI , 0.76 to 0.84 ; and hazard ratio , 0.82 ; 95 % CI , 0.79 to 0.85 , respectively ) . Regardless of total cholesterol level or coronary artery disease status  , statin therapy was associated with significant differences in mortality . Conclusions — Our data demonstrate that statin therapy is associated with better long-term mortality in older patients with HF . This study suggests a potential role for statins as an adjunct to current HF therapy . R and omized clinical trials are required to determine the role of these agents in improving outcomes in the large and growing group of patients with HF We prospect ively followed 202 patients with ischemic heart failure who underwent percutaneous coronary intervention ( PCI ) for acute myocardial infa rct ion ( left ventricular [ LV ] ejection fraction < 40 % ) . Patients were divided into 2 groups : groups I  ( simvastatin group , n = 106 , aged 60.8 + /- 10.3 years , men 71.7 % ) and II ( non-simvastatin group , n = 96 , aged 60.9 + /- 10.4 years , men 78.1 % ) . During 1-year clinical follow-up , simvastatin therapy was associated with a significant reduction in mortality ( 1.9 % vs 7.5 % , p = 0.048 ) , restenosis rate ( 25.7 % vs 43.1 % , p = 0.033 ) , and repeat PCI rate ( 25.7 % vs 43.1 % , p = 0.033 ) , and with significant improvement in LV ejection fraction ( 31 % to 42 % vs 32 % to 39 % , p = 0.042 ) . The event-free survival rate was higher in group I than in group II ( 79.8 % vs 57.0 % , p = 0.001 ) . In conclusion , simvastatin therapy improves LV systolic function and decreases mortality , restenosis , and repeat PCI rate in patients with ischemic heart failure who underwent PCI for acute myocardial infa rct ion BACKGROUND In retrospective studies , statin therapy has been related to decreased incidence of 
    Output:
    
Conclusions Lipophilic statin treatment shows significant decreases in all-cause mortality , cardiovascular mortality and hospitalization for worsening HF compared with rosuvastatin treatment .