***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 . ) The benefits of fixed-dose combination isosorbide dinitrate plus hydralazine ( ID/H ) in African-Americans with heart failure ( HF ) were established by the African-American Heart Failure Trial ( A-HeFT ) , which was terminated early because of a significant survival benefit of ID/H. The Extension to A-HeFT trial ( X-A-HeFT ) , design ed to make ID/H available for ethical reasons after A-HeFT termination , afforded an opportunity to further observe responsiveness and compliance with ID/H. In total 198 patients completing the A-HeFT took ID/H for an additional 209 + /- 116 days . Their age ( 57 + /- 13 years ) , cause and duration of HF , and HF medications were not different from all A-HeFT patients . New York Heart Association class at X-A-HeFT baseline was > or = III in 51 % of patients versus 100 % of all patients at A-HeFT baseline , remained unchanged in most patients , improved in 24 % , and worsened in only 9 % during X-A-HeFT . The average number of ID/H tablets taken during X-A-HeFT was 3.7 + /- 1.8 per day with compliance averaging 87 + /- 25 % . The most common adverse events , headache ( 34 % ) and dizziness ( 16 % ) , were less than in patients taking ID/H in A-HeFT , with only 6 % discontinuations for adverse events . The 6 % annualized mortality rate in X-A-HeFT was the same as for ID/H in A-HeFT . There were no statistically significant differences in baseline characteristics or outcomes in X-A-HeFT patients analyzed according to their A-HeFT r and omization . In conclusion , these results confirm the good compliance , tolerability , and responsiveness , with low mortality and improved symptoms , during treatment with ID/H observed in A-HeFT Resting hemodynamics improve during vasodilator administration in patients with congestive heart failure ( CHF ) , but the effects of these agents on exercise is unknown . Twenty-two patients with class II or III CHF performed bicycle exercise to symptomatic maximum before and 90 minutes after r and om doubleblind administration of oral hydralazine ( 100 mg ) and isosorbide dinitrate ( 40 mg ) ( 11 patients , group 1 ) or placebo ( 11 patients , group 2 ) . Exercise duration was unchanged after treatment in either group . Maximal oxygen consumption changed insignificantly in both groups , from 12.6 ± 1.2 ( SEM ) to 13.6 ± 1.6 ml/kg/min in group 1 , and from 11.7 ± 1.4 to 13.4 ± 1.7 ml/kg/min in group 2 . Maximal cardiac index was unchanged in both group 1 ( 4.00 ± 0.33 to 4.41 ± 0.29 1/min/m2 ) and group 2 ( 4.11 ± 0.43 to 4.14 ± 0.42 1/min/m2 ) . Systemic vascular resistance at peak exercise was also unchanged in both group 1 ( 14.1 1.6 to 11.8 1.0 units ) and group 2 ( 14.7 1.6 to 13.5 ± 1.6 units ) . At submaximal exercise ( 300 kilopond-meters/min ) , however , cardiac index after treatment increased in group 1 ( 0.51 + 0.18 1/min/m2,p < 0.05 ) and systemic vascular resistance decreased ( -3.3 ± 1.3 units , p < 0.05 ) , but were unchanged in group 2 . Thus , although vasodilators do not improve maximal exercise capacity acutely , they can improve hemodynamics at lower work loads which may , therefore , be better tolerated in patients with CHF The efficacy of orally administered isosorbide dinitrate ( IS ) has been question ed . Recently vasodilators have been shown to lower left ventricular filling pressure ( LVFP ) and raise cardiac output in heart failure . In the present study oral IS was evaluated in 12 patients with high LVFP due to heart failure . After right heart catheterization , patients with LVFP > 14 mm Hg were r and omized double-blind to receive either 20 mg IS or placebo ( P ) . Supine heart rate ( HR ) , arterial pressure ( BP ) , and LVFP were monitored for five hours . After this the alternate drug ( P or IS ) was given , followed by five more hours of monitoring . In the 12 patients after receiving IS , LVFP reached a peak reduction of 6.7 mm Hg ( -26 % , P < 0.005 ) at 30 min . Significant reduction persisted for 4.5 hours . Blood pressure fell concomitantly with the LVFP . At 60 min HR was unchanged , systolic BP was reduced by 8.9 mm Hg ( P < 0.025 ) and diastolic BP by 6.3 mm Hg ( P < 0.005 ) . In the ten patients receiving P , control values were not significantly different from those given IS , and after receiving  P , HR , BP , and LVFP failed to change significantly over the next five hours . Thus , oral IS produces a sustained reduction in LVFP and therefore merits further evaluation as chronic therapy for left ventricular failure Vasodilators are known to be effective in improving the hemodynamics of congestive heart failure by increasing cardiac output and reducing left ventricular filling pressure ( LVFP ) . Long acting agents are needed to augment the practicality and availability of chronic vasodilator therapy . In the present study the vascular effects of chewable isosorbide dinitrate ( CHIS ) , sublingual nitroglycerin ( NTG ) and placebo ( P ) were compared in eight patients with high LVFP due to heart failure . Patients with LVFP ( pulmonary wedge pressure ) over 14 mm Hg were given CHIS , 10 mg , NTG , 0.6 mg , and P , two chewable tablets , in r and om fashion . Heart rate ( HR ) , blood pressure ( BP ) , and LVFP were monitored for three hours after each drug . HR was not significantly affected by any drug , although it rose slightly after NTG and fell after CHIS . Significant reduction of BP occurred only after NTG , with peak effect at five minutes , but lasting only 15 minutes . NTG reduced LVFP 5.1 mm Hg ( 19.5 % , P < 0.05 ) , at peak effect , but LVFP was no longer significantly lower by 20 minutes after NTG . After CHIS , LVFP fell significantly within five minutes , reached a peak reduction of 8.6 mm Hg ( 32.7 % , P < 0.01 ) at 15 minutes , and remained significantly lower through three hours . Thus CHIS provides a nitrate action of rapid onset and sustained effect that may be useful for chronic vasodilator therapy of heart failure We compared the effects of Hydralazine and Isosorbide dinitrate ( ISDN ) with those of an angiotensin-converting-enzyme inhibitor , captopril on mortality in patients with chronic congestive heart failure ( NYHA class III and IV ) . Patients receiving conventional treatment with digoxin and diuretics  were r and omly assigned to receive either placebo ( n = 51 ) , hydralazine-ISDN . ( n = 50 ) or captopril ( n = 52 ) in a double blind trial . At the end of 6 months there were 14 deaths in the placebo group ( 27.4 % ) as compared with 11 deaths in the hydralazine-ISDN group (22%)--a mortality reduction of 20 % ( P > 0.05 ) and 10 deaths in the captopril group (19.2%)--a mortality reduction of 30 % ( p > 0.05 ) . At the end of one year , mortality was 50 % , 42 % and 30 % in the placebo , hydralazine-ISDN and captopril groups respectively with a mortality reduction of 16 % in the hydralazine-ISDN group ( p > 0.05 ) and 40 % in the captopril group ( p < 0.05 ) compared to the placebo group . The mortality reduction was mainly due to reduction in deaths attributed to progressive heart failure . The data suggests that the addition of captopril to conventional treatment significantly reduces mortality in patients with severe congestive heart failure .  Hydralazine-isorobide dinitrate also reduced mortality but statistically this was not significant A r and omized double-blind crossover trial included 16 patients with severe congestive heart failure who received isosorbide dinitrate or placebo for eight weeks , and then the opposite treatment for eight more weeks . All patients received their usual maintenance therapy with digitalis and diuretics . Seven morbid events occurred during 85 patient-weeks of isosorbide dinitrate therapy compared with 17 during 76 patient-weeks of placebo .  Severity of congestive heart failure improved in all eight patients who received isosorbide dinitrate compared with two patients who showed improvement and five whose symptoms became worse with placebo . No significant differences in physical findings , cardiac dimensions , or resting hemodynamics were observed . Maximal exercise duration increased significantly by 2.54 minutes with isosorbide dinitrate therapy , and rose insignificantly by 1.24 minutes with placebo . This preliminary trial suggests that long-term vasodilator therapy may be clinical ly beneficial in congestive heart failure We evaluated the effects of intravenous hydralazine ( 5 to 30 mg ) and oral nifedipine ( 20 to 80 mg ) on plasma catecholamines , renin , and aldosterone in 18 patients with severe chronic heart failure . Both drugs result ed in a significant decrease in systemic vascular resistance and mean systemic blood pressure , and led to an increase in cardiac output . Baseline plasma norepinephrine concentration was elevated in most patients ; however , augmentation of cardiac output with both drugs did not decrease the values of this hormone ( from 870 + /- 128 to 946 + /- 161 pg/ml with hydralazine and from 1088 + /- 260 to 1106 + /- 187 pg/ml with nifedipine ) . Plasma epinephrine level was also elevated at baseline and did not change significantly following nifedipine therapy ( 164 + /- 44 vs 199 + /- 54 pg/ml ) , but increased in most patients following the administration of hydralazine ( from 105 + /- 45 to 153 + /- 27 pg/ml , p less than 0.01 ) . The renin-aldosterone system was activated in our patients and also demonstrated a different response to both drugs . Hydralazine therapy did not change 
    Output:
    
Compared to placebo , H&N reduces mortality in patients with CHF .
Whether race or background therapy influences benefit is uncertain , but on direct comparison H&N appears inferior to ACEI .
There is little evidence to support the use of either drug alone in CHF