***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: IMPORTANCE Diastolic heart failure ( ie , heart failure with preserved ejection fraction ) is a common condition without established therapy , and aldosterone stimulation may contribute to its progression . OBJECTIVE To assess the efficacy and safety of long-term aldosterone receptor blockade in heart failure with preserved ejection fraction . The primary objective was to determine whether spironolactone is superior to placebo in improving diastolic function and maximal exercise capacity in patients with heart failure with preserved ejection fraction . DESIGN AND SETTING The Aldo-DHF trial , a multicenter , prospect i ve , r and omized , double-blind , placebo-controlled trial conducted between March 2007 and April 2012 at 10 sites in Germany and Austria that included 422 ambulatory patients ( mean age , 67 [ SD , 8 ] years ; 52 % female ) with chronic New York Heart Association class II or III heart failure , preserved left ventricular ejection fraction of 50 % or greater , and evidence of diastolic dysfunction . INTERVENTION Patients were r and omly assigned to receive 25 mg of spironolactone once daily  ( n=213 )  or matching placebo  ( n=209 ) with 12 months of follow-up . MAIN OUTCOME MEASURES The equally ranked co- primary end points were changes in diastolic function ( E/e ' ) on echocardiography and maximal exercise capacity ( peak VO2 ) on cardiopulmonary exercise testing , both measured at 12 months . RESULTS Diastolic function ( E/e ' ) decreased from 12.7 ( SD , 3.6 ) to 12.1 ( SD , 3.7 ) with spironolactone and increased from 12.8 ( SD , 4.4 ) to 13.6 ( SD , 4.3 ) with placebo ( adjusted mean difference , -1.5 ; 95 % CI , -2.0 to -0.9 ; P < .001 ) . Peak VO2 did not significantly change with spironolactone vs placebo ( from 16.3 [ SD , 3.6 ] mL/min/kg to 16.8 [ SD , 4.6 ] mL/min/kg and from 16.4 [ SD , 3.5 ] mL/min/kg to 16.9 [ SD , 4.4 ] mL/min/kg , respectively ; adjusted mean difference , + 0.1 mL/min/kg ; 95 % CI , -0.6 to + 0.8 mL/min/kg ; P = .81 ) .  Spironolactone induced reverse remodeling ( left ventricular mass index declined ; difference , -6 g/m2 ; 95 % CI , -10 to-1 g/m2 ; P = .009 ) and improved neuroendocrine activation ( N-terminal pro-brain-type natriuretic peptide geometric mean ratio , 0.86 ; 95 % CI , 0.75 - 0.99 ; P = .03 ) but did not improve heart failure symptoms or quality of life and slightly reduced 6-minute walking distance ( -15 m ; 95 % CI , -27 to -2 m ; P = .03 ) . Spironolactone also modestly increased serum potassium levels ( + 0.2 mmol/L ; 95 % CI , + 0.1 to + 0.3 ; P < .001 ) and decreased estimated glomerular filtration rate ( -5 mL/min/1.73 m2 ; 95 % CI , -8 to -3 mL/min/1.73 m2 ; P < .001 ) without affecting hospitalizations . CONCLUSIONS AND RELEVANCE In this r and omized controlled trial , long-term aldosterone receptor blockade improved left ventricular diastolic function but did not affect maximal exercise capacity , patient symptoms , or quality of life in patients with heart failure with preserved ejection fraction . Whether the improved left ventricular function observed in the Aldo-DHF trial is of clinical significance requires further investigation in larger population s. TRIAL REGISTRATION clinical trials.gov Identifier : IS RCT N94726526 ; Eudra-CT No : 2006 - 002605 - 31 The  efficacy and tolerability of eplerenone , a selective aldosterone blocker , was assessed when added to existing antihypertensive therapy with an ACE inhibitor or an angiotensin II receptor blocker ( ARB ) . Hypertensive patients ( n=341 ) whose blood pressure ( BP ) was not controlled despite ACE inhibitor or ARB  were r and omized ( double-blind ) to receive 50 mg eplerenone ( increasing to 100 mg if required ) once daily or placebo for 8 weeks . Diastolic and systolic BP and adverse events were recorded . By study end ( week 8) , mean seated diastolic BP was significantly reduced from week 0 among patients receiving eplerenone/ARB ( −12.7±0.81 mm Hg ) compared with those receiving placebo/ARB ( −9.3±0.83 mm Hg ) . The change in mean seated diastolic BP was −9.9±0.88 mm Hg in eplerenone/ACE inhibitor patients and −8.0±0.86 mm Hg in placebo/ACE inhibitor patients ( P = NS ) . Systolic BP levels were also significantly lower at week 8 for eplerenone/ACE inhibitor ( −13.4±1.35 mm Hg ) and eplerenone/ARB ( −16.0±1.37 mm Hg ) patients , respectively , compared with placebo/ACE inhibitor ( −7.5±1.31 mm Hg ) and placebo/ARB patients ( −9.2±1.41 mm Hg ) . Adverse events were generally nonsevere and not significantly different between eplerenone and placebo . This study demonstrated that in patients whose BP was not controlled with an ACE inhibitor or ARB , the addition of eplerenone over an 8-week period significantly lowered systolic BP in both groups and diastolic BP in ARB patients . Selective aldosterone blockade with eplerenone , therefore , may be useful add-on therapy in hypertensive patients inadequately controlled on ACE inhibitor or ARB alone Background — LCI699 , a novel inhibitor of aldosterone synthase , reduces serum aldosterone , and may have benefit in the treatment of hypertension . Methods and Results — We performed the first double-blind , r and omized trial with LCI699 in patients with primary hypertension . We r and omized 524 patients to LCI699 0.25 mg once daily ( n=92 ) , 0.5 mg once daily ( n=88 ) , 1.0 mg once daily ( n=86 ) , and 0.5 mg twice daily ( n=97 ) ; eplerenone 50 mg twice daily ( n=84 ) ; or placebo ( n=77 ) for 8 weeks . Adrenocorticotropic hormone ( 250 & mgr;g IV ) stimulation testing was performed in a subset of patients to quantify the selectivity of LCI699 for aldosterone synthase compared with 11-&bgr;-hydroxylase . Reductions in clinic diastolic blood pressure were significant for LCI699 1.0 mg ( −7.1 mm Hg ; P=0.0012 ) and eplerenone 50 mg twice daily ( −7.9 mm Hg ; P<0.0001 ) compared with placebo ( −2.6 mm Hg ) but not other doses of LCI699 . Significant reductions in clinic systolic blood pressure were observed with all doses of LCI699 ( P<0.005 or better ) and eplerenone ( P<0.0001 ) . All doses of LCI699 significantly reduced 24-hour ambulatory blood pressure compared with placebo ( P<0.01 ) . Adrenocorticotropic hormone stimulation of cortisol was suppressed in ≈20 % of subjects receiving LCI699 at a total daily dose of 1.0 mg . Safety and tolerability were similar among LCI699 , placebo , and eplerenone . Conclusions — Aldosterone synthase inhibition with LCI699 significantly lowered clinic and ambulatory blood pressure . A minority of subjects developed blunted adrenocorticotropic hormone – stimulated release of cortisol . These results support additional research to evaluate use of aldosterone synthase inhibition in primary hypertension and /or patients characterized by aldosterone excess . Clinical Trial Registration — URL : http://www . clinical trials.gov . Unique identifier : NCT00758524 Aims Mineralocorticoid receptor antagonists ( MRAs ) improve outcomes in patients with heart failure and reduced left ventricular ejection fraction ( HFrEF ) , but their use is limited by hyperkalaemia and /or worsening renal function ( WRF ) . BAY 94 - 8862 is a highly selective and strongly potent non-steroidal MRA . We investigated its safety and tolerability in patients with HFrEF associated with mild or moderate chronic kidney disease ( CKD ) . Methods and results This r and omized , controlled , phase II trial consisted of two parts . In part A , the safety and tolerability of oral BAY 94 - 8862 [ 2.5 , 5 , or 10 mg once daily ( q.d . ) ] was assessed in 65 patients with HFrEF and mild CKD . In part B , BAY 94 - 8862 ( 2.5 , 5 , or 10 mg q.d . , or 5 mg twice daily ) was compared with placebo and open-label spironolactone ( 25 or 50 mg/day ) in 392 patients with HFrEF and moderate CKD . BAY 94 - 8862 was associated with significantly smaller mean increases in serum potassium concentration than spironolactone ( 0.04–0.30 and 0.45 mmol/L , respectively , P < 0.0001–0.0107 ) and lower incidences of hyperkalaemia ( 5.3 and 12.7 % , respectively , P = 0.048 ) and WRF . BAY 94 - 8862 decreased the levels of B-type natriuretic peptide ( BNP ) , amino-terminal proBNP , and albuminuria at least as much as spironolactone . Adverse events related to BAY 94 - 8862 were infrequent and mostly mild . Conclusion In patients with HFrEF and moderate CKD , BAY 94 - 8862 5–10 mg/day was at least as effective as spironolactone 25 or 50 mg/day in decreasing biomarkers of haemodynamic stress , but it was associated with lower incidences of hyperkalaemia and WRF There is currently limited data on which drug should be used to improve blood pressure ( BP ) control in patients with resistant hypertension . This study was design ed to assess the effect of the addition of 25 mg of spironolactone on BP in patients with resistant arterial hypertension . Patients with office systolic BP > 140 mm Hg or diastolic BP > 90 mm Hg despite treatment with at least 3 antihypertensive drugs , including a diuretic , were enrolled in this double-blind , placebo-controlled , multicenter trial . One hundred seventeen patients were r and omly assigned to receive spironolactone ( n=59 ) or a placebo ( n=58 ) as an add-on to their antihypertensive medication , by the method of simple r and omization . Analyses were done with 111 patients ( 55 in the  spironolactone  and 56 in the  placebo  groups ) . At 8 weeks , the primary end points , a difference in mean fall of BP on daytime ambulatory BP monitoring ( ABPM ) , between the groups was −5.4 mm Hg ( 95%CI −10.0 ; −0.8 ) for systolic BP ( P=0.024 ) and −1.0 mm Hg ( 95 % CI −4.0 ; 2.0 ) for diastolic BP ( P=0.358 ) . The APBM nighttime systolic , 24-hour ABPM systolic , and office systolic BP values were significantly decreased by spironolactone ( difference of −8.6 , −9.8 , and −6.5 mm Hg ; P=0.011 , 0.004 , and 0.011 ) , whereas the fall of the respective diastolic BP values was not significant ( −3.0 , −1.0 , and −2.5 mm Hg ; P=0.079 , 0.405 , and 0.079 ) . The adverse events in both groups were comparable . In conclusion , spironolactone is an effective drug for lowering systolic BP in patients with resistant arterial hypertension The effects of spironolactone or metoprolol added to a conventional treatment protocol on QT dispersion , which is accepted as a sudden cardiac death predictor , were evaluated in heart failure patients . ? A total of 105 New York Heart Association class III patients were included in this study . The conventional treatment protocol was st and ardized by giving ramipril , furosemide , and digoxin to all patients for 3 weeks at the same doses . At the end of this period , the patients were divided into three groups . Conventional treatment was continued in group 1 , 25 mg spironolactone was 
    Output:
    
Conclusion Inhibition of the mineralocorticoid receptor with MRAs  in patients with hypertension and heart failure does not change the risk of myocardial infa rct ion , stroke and bleeding events .
Our meta- analysis confirms the favourable effects of MRAs on total and cardiovascular mortality .
These data suggest that MRAs can be considered as safe regarding their effects on haemostasis in patients with hypertension and heart failure