***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 We compared the angiotensin receptor-neprilysin inhibitor LCZ696 with enalapril in patients who had heart failure with a reduced ejection fraction . In previous studies , enalapril improved survival in such patients . METHODS In this double-blind trial , we r and omly assigned 8442 patients with class II , III , or IV heart failure and an ejection fraction of 40 % or less to receive either  LCZ696  ( at a dose of 200 mg twice daily ) or enalapril ( at a dose of 10 mg twice daily ) , in addition to recommended therapy . The primary outcome was a composite of death from cardiovascular causes or hospitalization for heart failure , but the trial was design ed to detect a difference in the rates of death from cardiovascular causes . RESULTS The trial was stopped early , according to prespecified rules , after a median follow-up of 27 months , because the boundary for an overwhelming benefit with LCZ696 had been crossed . At the time of study closure , the primary outcome had occurred in 914 patients ( 21.8 % ) in the LCZ696 group and 1117 patients ( 26.5 % ) in the enalapril group ( hazard ratio in the LCZ696 group , 0.80 ; 95 % confidence interval [ CI ] , 0.73 to 0.87 ; P<0.001 ) . A total of 711 patients ( 17.0 % ) receiving LCZ696 and 835 patients ( 19.8 % ) receiving enalapril  died ( hazard ratio for death from any cause , 0.84 ; 95 % CI , 0.76 to 0.93 ; P<0.001 ) ; of these patients , 558 ( 13.3 % ) and 693 ( 16.5 % ) , respectively , died from cardiovascular causes ( hazard ratio , 0.80 ; 95 % CI , 0.71 to 0.89 ; P<0.001 ) . As compared with enalapril , LCZ696 also reduced the risk of hospitalization for heart failure by 21 % ( P<0.001 ) and decreased the symptoms and physical limitations of heart failure ( P=0.001 ) . The  LCZ696 group had higher proportions of patients with hypotension and nonserious angioedema but lower proportions with renal impairment , hyperkalemia , and cough than the enalapril group . CONCLUSIONS LCZ696 was superior to enalapril in reducing the risks of death and of hospitalization for heart failure . ( Funded by Novartis ; PARADIGM-HF Clinical Trials.gov number , NCT01035255 . ) AIMS We identified easily obtained baseline characteristics associated with outcomes in patients with chronic heart failure ( HF ) and elevated heart rate ( HR ) receiving contemporary guideline -recommended therapy in the SHIFT trial , and used them to develop a prognostic model . METHODS We selected the 10 best predictors for each of four outcomes ( cardiovascular death or HF hospitalisation ; all-cause mortality ; cardiovascular mortality ; and HF hospitalisation ) . All variables with p<0.05 for association were entered into a forward stepwise Cox regression model . Our initial analysis excluded baseline therapies , though r and omisation to ivabradine or placebo was forced into the model for the composite endpoint and HF hospitalisation . RESULTS Increased resting HR , low ejection fraction , raised creatinine , New York Heart Association class III/IV , longer duration of HF , history of left bundle branch block , low systolic blood pressure and , for three models , age were strong predictors of all outcomes . Additional predictors were low body mass index , male gender , ischaemic HF , low total cholesterol , no history of hyperlipidaemia or dyslipidaemia and presence of atrial fibrillation/flutter . The c-statistics for the four outcomes ranged from 67.6 % to 69.5 % . There was no evidence for lack of fit of the models with the exception of all-cause mortality ( p=0.017 ) . Similar results were found including baseline therapies . CONCLUSION The SHIFT Risk Model includes simple , readily obtainable clinical characteristics to produce important prognostic information in patients with chronic HF , systolic dysfunction , and elevated HR . This may help better calibrate management to individual patient risk Background and Purpose — In heart failure ( HF ) , left ventricular ejection fraction ( LVEF ) is inversely associated with mortality and cardiovascular outcomes . Its relationship with stroke is controversial , as is the effect of antithrombotic treatment . We studied the relationship of LVEF with stroke and cardiovascular events in patients with HF and the effect of different antithrombotic treatments . Methods — In the Warfarin Versus Aspirin in Reduced Ejection Fraction ( WARCEF ) trial , 2305 patients with systolic HF ( LVEF⩽35 % ) and sinus rhythm were r and omized to warfarin or aspirin and followed for 3.5±1.8 years . Although no differences between treatments were observed on primary outcome ( death , stroke , or intracerebral hemorrhage ) , warfarin decreased the stroke risk . The present report compares the incidence of stroke and cardiovascular events across different LVEF and treatment subgroups . Results — Baseline LVEF was inversely and linearly associated with primary outcome , mortality and its components ( sudden and cardiovascular death ) , and HF hospitalization , but not myocardial infa rct ion . A relationship with stroke was only observed for LVEF of < 15 % ( incidence rates : 2.04 versus 0.95/100 patient-years ; P=0.009 ) , which more than doubled the adjusted stroke risk ( adjusted hazard ratio , 2.125 ; 95 % CI , 1.182–3.818 ; P=0.012 ) . In warfarin-treated patients , each 5 % LVEF decrement significantly increased the stroke risk ( adjusted hazard ratio , 1.346 ; 95 % CI , 1.044–1.737 ; P=0.022 ; P value for interaction=0.04 ) . Conclusions — In patients with systolic HF and sinus rhythm , LVEF is inversely associated with death and its components , whereas an association with stroke exists for very low LVEF values . An interaction with warfarin treatment on stroke risk may exist . Clinical Trial Registration — URL : http://www . clinical trials.gov . Unique identifier : NCT00041938 AIMS The angiotensin-receptor-neprilysin inhibitor ( ARNI ) LCZ696 reduced cardiovascular deaths and all-cause mortality compared with enalapril in patients with chronic heart failure in the prospect i ve comparison of ARNI with an Angiotensin-Converting Enzyme Inhibitor to Determine Impact on Global Mortality and Morbidity in Heart Failure ( PARADIGM-HF ) trial . To more completely underst and the components of this mortality benefit , we examined the effect of LCZ696 on mode of death . METHODS AND RESULTS PARADIGM-HF was a prospect i ve , double-blind , r and omized trial in 8399 patients with chronic heart failure , New York Heart Association Class II-IV symptoms , and left ventricular ejection fraction ≤40 % receiving guideline -recommended medical therapy and followed for a median of 27 months . Mode of death was adjudicated by a blinded clinical endpoints committee . The majority of deaths were cardiovascular ( 80.9 % ) , and the risk of cardiovascular death was significantly reduced by treatment with LCZ ( hazard ratio , HR 0.80 , 95 % CI 0.72 - 0.89 , P < 0.001 ) . Among cardiovascular deaths , both sudden cardiac death ( HR 0.80 , 95 % CI 0.68 - 0.94 , P = 0.008 ) and death due to worsening heart failure ( HR 0.79 , 95 % CI 0.64 - 0.98 , P = 0.034 ) were reduced by treatment with LCZ696 compared with enalapril . Deaths attributed to other cardiovascular causes , including myocardial infa rct ion and stroke , were infrequent and distributed evenly between treatment groups , as were non-cardiovascular deaths . CONCLUSIONS LCZ696 was superior to enalapril in reducing both sudden cardiac deaths and deaths from worsening heart failure , which accounted for the majority of cardiovascular deaths . CLINICAL TRIAL REGISTRATION https:// clinical trials.gov/ , NCT01035255 BACKGROUND Angiotensin II type 1 receptor blockers have favourable effects on haemodynamic measurements , neurohumoral activity , and left-ventricular remodelling when added to angiotensin-converting-enzyme ( ACE ) inhibitors in patients with chronic heart failure ( CHF ) . We aim ed to find out whether these drugs improve clinical outcome . METHODS Between March , 1999 , and November , 1999 , we enrolled 2548 patients with New York Heart Association functional class II-IV CHF and left-ventricular ejection fraction 40 % or lower , and who were being treated with ACE inhibitors .  We r and omly assigned patients c and esartan ( n=1276 , target dose 32 mg once daily ) or placebo ( n=1272 ) . At baseline , 55 % of patients were also treated with beta blockers and 17 % with spironolactone . The primary outcome of the study was the composite of cardiovascular death or hospital admission for CHF . Analysis was done by intention to treat . FINDINGS The median follow-up was 41 months . 483 ( 38 % ) patients in the c and esartan group and 538 ( 42 % ) in the placebo group experienced the primary outcome ( unadjusted hazard ratio 0.85 [ 95 % CI 0.75 - 0.96 ] , p=0.011 ; covariate adjusted p=0.010 ) . C and esartan reduced each of the components of the primary outcome significantly , as well as the total number of hospital admissions for CHF . The benefits of c and esartan were similar in all predefined subgroups , including patients receiving baseline beta blocker treatment . INTERPRETATION The addition of c and esartan to ACE inhibitor and other treatment leads to a further clinical ly important reduction in relevant cardiovascular events in patients with CHF and reduced left-ventricular ejection fraction Background — The factors that determine the risk for sudden death or implantable cardioverter defibrillator therapy in patients receiving cardiac resynchronization therapy ( CRT ) therapies  are largely unknown . Methods and Results — We hypothesized that clinical measures of heart failure severity and the presence of comorbid conditions would predict the risk of malignant arrhythmias in the 1520 patients enrolled in the Comparison of Medical Therapy , Pacing , and Defibrillation in Heart Failure ( COMPANION ) Trial . Outcomes in the CRT group after implantable cardioverter defibrillator therapy were also evaluated . The CRT-defibrillator device reduced the risk of sudden death by 56 % compared with drug therapy ( 17 of 595 [ 2.9 % ] versus 18 of 308 [ 5.8 % ] , P<0.02 ) . CRT therapy was not associated with sudden death risk reduction ( 48 of 617 [ 7.8 % ] ) . Other factors associated with reduced sudden death risk were left ventricular ejection fraction > 20 % ( HR , 0.55 [ 95 % CI , 0.35 to 0.87 ] ; P=0.01 ) , QRS duration > 160 ms ( HR , 0.63 [ 95 % CI , 0.40 to 0.997 ] ; P=0.05 ) , and female gender ( HR , 0.56 [ 95 % CI , 0.34 to 0.94 ] ; P=0.003 ) . The risk for sudden death was increased by advanced New York Heart Association class IV heart failure ( HR , 2.62 [ 95 % CI , 1.61 to 4.26 ] ; P<0.011 ) and renal dysfunction ( HR , 1.69 [ 95 % CI , 1.06 to 2.69 ] ; P=0.03 ) . An appropriate shock was experienced in 88 ( 15 % ) of the 595 CTR-D patients . In the CRT-defibrillator patients , female gender ( HR , 0.54 [ 95 % CI , 0.31 to 0.94 ] ; P=0.03 ) and use of neurohormonal antagonists were associated with reduced risk . Class IV heart failure status increased risk . Appropriate implantable cardioverter defibrillator therapy was positively associated with risk of death or all-cause hospitalization ( HR , 1.57 ; P<0.002 ) , pump failure death or hospitalization ( HR , 2.35 ; P<0.001 ) , and sudden death ( HR , 2.99 ; P=0.03 ) , but not total mortality ( HR , 1.3 ; P=0.28 ) . Conclusions — In CRT c and i date s , sudden cardiac 
    Output:
    
In our meta- analysis of contemporary r and omized trials of drug therapy for heart failure with reduced ejection fraction , the rate of ICD use was low and associated with a decreased risk in both all-cause mortality and sudden cardiac death .
This benefit was still present in trials with new medical therapy