***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 
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    Input: BACKGROUND Renin-angiotensin system inhibitors have renoprotective effects in patients with chronic kidney disease , but most patients treated with these drugs have residual urinary albumin excretion . Some small clinical studies show that mineralocorticoid receptor blockade reduces albuminuria . Our study aim ed to examine the beneficial effects of addition of a selective aldosterone antagonist , eplerenone , to renin-angiotensin system inhibitors in hypertensive patients with non-diabetic chronic kidney disease . METHODS In this double-blind , r and omised , placebo-controlled trial , we enrolled hypertensive patients , aged 20–79 years , with albuminuria ( urinary albumin-to-creatinine ratio [ UACR ] in the first morning void urine of 30–599 mg/g ) , an estimated glomerular filtration rate of 50 mL/min per 1·73 m2 or more , and who had received an angiotensin-converting enzyme inhibitor , an angiotensin receptor blocker , or both , for at least 8 weeks . Participants were from 59 clinics and hospitals in Japan . Eligible patients were r and omly assigned ( 1:1 ) , stratified by baseline characteristics , to either low-dose eplerenone ( 50 mg/day ) or placebo , with continuation of st and ard antihypertensive treatment to attain therapeutic goals ( < 130/80 mm Hg ) for 52 weeks . We assessed efficacy in all patients who received allocated treatment , provided a baseline and post-treatment urine sample , and remained in follow-up . We assessed safety in all patients who received allocated treatment . The primary efficacy measure was percent change in UACR in the first morning void urine at week 52 from baseline . The trial is registered at the clinical trials registry of University Hospital Medical Information Network ( UMIN ) , trial identification number UMIN000001803 . FINDINGS Between April 1 , 2009 , and March 31 , 2012 , we r and omly allocated 170 patients to the eplerenone group and 166 patients to the  placebo group . In the primary efficacy analysis , mean percent change in UACR from baseline was −17·3 % ( 95 % CI −33·65 to −0·94 ) for 158 patients in the eplerenone group compared with 10·3 % ( −6·75 to 22·3 ) for 146 patients in the placebo group ( absolute difference −27·6 % [ –51·15 to −3·96 ] ; p=0·0222 ) . In the safety analyses , 53 ( 31 % ) of 169 patients in the eplerenone  group had adverse events ( five serious ) , as did 49 ( 30 % ) of 163 in the placebo group ( seven serious ) . Although mean serum potassium concentration was higher in the eplerenone group than the placebo group , severe hyperkalaemia ( > 5·5 mmol/L ) was not recorded in either group . INTERPRETATION Addition of low-dose eplerenone to renin-angiotensin system inhibitors might have renoprotective effects through reduction of albuminuria in hypertensive patients with non-diabetic chronic kidney disease , without serious safety concerns . FUNDING Pfizer BACKGROUND Eplerenone , a selective aldosterone blocker ( SAB ) that is highly specific for the aldosterone receptor , has the potential to be efficacious in the treatment of hypertension . METHODS This 8-week , multicenter , double-blind , placebo-controlled trial assessed the efficacy , safety , and tolerability of eplerenone in eligible patients r and omized to eplerenone 50 , 100 , or 400 mg once daily ; eplerenone 25 , 50 , or 200 mg twice daily ; spironolactone 50 mg twice daily ; or placebo .  The primary efficacy variable was the adjusted mean change in baseline to final visit for seated diastolic blood pressure ( DBP ) . RESULTS Of 417 r and omized patients , 409 were evaluated for efficacy . The adjusted mean change from baseline to final visit in seated and st and ing systolic blood pressure ( SBP ) and DBP was significantly greater ( P < .05 ) in all eplerenone groups than in the placebo group . The adjusted mean change in 24-h ambulatory blood pressure monitoring ( ABPM ) measurements of SBP and DBP also documented a 24-h duration significantly greater ( P < .05 ) than placebo in eplerenone-treated patients . For all measurements , the antihypertensive effect of eplerenone increased in a dose-response fashion . Eplerenone ( 100 mg ) reduced BP by 75 % compared with spironolactone ( 100 mg ) and had an adverse events incidence rate similar to placebo . No anti and rogenic or progestational effects or clinical ly relevant safety issues were observed in eplerenone-treated patients . However , one spironolactone-treated patient reported menstrual irregularities . CONCLUSIONS Eplerenone doses of 50 to 400 mg once daily are well tolerated and effective in reducing BP in patients with mild-to-moderate hypertension during a 24-h period 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 OBJECTIVES The purpose of this study was to evaluate the efficacy and tolerability of monotherapy with the selective aldosterone blocker eplerenone in both black and white patients with hypertension . BACKGROUND Essential hypertension and cardiovascular-renal-target organ damage is more prevalent in black than white adults in the U.S. METHODS Black ( n = 348 ) and white ( n = 203 ) patients with mild-to-moderate hypertension were r and omized to double-blind treatment with eplerenone 50 mg , the angiotensin II receptor antagonist losartan 50 mg , or placebo once daily . Doses were increased if blood pressure remained uncontrolled . The primary end point was change in mean diastolic blood pressure ( DBP ) after 16 weeks of therapy . RESULTS Adjusted mean changes from baseline in DBP were -5.3 + /- 0.7 , -10.3 + /- 0.7 , and -6.9 + /- 0.6 mm Hg in the placebo , eplerenone-treated , and losartan-treated groups , respectively ( mean + /- SE , p < 0.001 eplerenone vs. placebo , p < 0.001 eplerenone vs. losartan ) . In black patients , DBP decreased by -4.8 + /- 1.0 , -10.2 + /- 0.9 , and -6.0 + /- 0.9 mm Hg for the placebo , eplerenone-treated , and losartan-treated groups , respectively ( mean + /- SE , p < 0.001 eplerenone vs. placebo , p < 0.001 eplerenone vs. losartan ) , whereas in white patients , DBP decreased by -6.4 + /- 1.0 , -11.1 + /- 1.1 , and -8.4 + /- 1.0 mm Hg , respectively ( p = 0.001 eplerenone vs. placebo , p = 0.068 for eplerenone vs. losartan ) . For reduction of systolic blood pressure ( SBP ) , eplerenone was superior to placebo and losartan in all patients combined and in black patients , and was superior to placebo in white patients . Eplerenone was as effective as losartan in reducing SBP and DBP in the high renin patient , but more effective than losartan in the low renin patient . Similarly , eplerenone was at least as effective as losartan in patients with differing baseline levels of aldosterone . Both eplerenone and losartan were well tolerated . CONCLUSIONS The antihypertensive effect of eplerenone was equal in black and white patients and was superior to losartan in black patients AIMS Our objective was to create a simple prognostic risk score for patients with systolic heart failure and mild symptoms . We then assessed the efficacy of eplerenone across different categories of risk . METHODS AND RESULTS The Eplerenone in Mild Patients Hospitalization and Survival Study in Heart Failure trial ( EMPHASIS-HF ) was an international r and omized trial , comparing eplerenone with placebo in 2737 patients with systolic heart failure and mild symptoms . The primary outcome was a composite of cardiovascular death or hospitalization for heart failure , over a median 2.1 years follow-up . Using multivariable Cox modelling age , sex , systolic blood pressure , estimated glomerular filtration rate , diabetes , BMI , haemoglobin , prior heart failure ( HF ) hospitalization , prior myocardial infa rct ion/coronary artery bypass surgery ( CABG ) , and heart rate were identified as strong independent risk factors . Estimates from the model were converted into a simple integer risk score which was categorized into three groups of low- , medium- , and high risk . In placebo patients , the rates ( per 100 patient-years ) for the primary outcome were 7.6 , 19.0 , and 39.4 in the low- , medium- , and high-risk groups , respectively . On eplerenone , these rates were reduced to 5.6 , 12.2 , and 24.2 , respectively . Eplerenone was beneficial across all risk categories and the hazard ratios were similar . The absolute treatment benefit was greatest among those at highest risk . Similar patterns emerged for all-cause mortality and for all HF hospitalizations . CONCLUSION This easy-to-use integer risk score should be of value in quantifying individual patient risk in patients with systolic HF and mild symptoms . The relative benefits of eplerenone appeared consistent across the whole spectrum of risk , including those at lower risk 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 
    Output:
    
Meta- analysis of these studies showed a reduction in systolic blood pressure of 9.21 mmHg ( 95 % CI -11.08 to -7.34 ; I2 = 58 % ) and a reduction of diastolic pressure of 4.18 mmHg ( 95 % CI -5.03 to -3.33 ; I2 = 0 % ) ( moderate quality evidence ) .There may be a dose response effect for eplerenone in the reduction in systolic blood pressure at doses of 400 mg/day .
Overall there does not appear to be a clinical ly important dose response in lowering systolic or diastolic blood pressure at eplerenone doses of 50 mg to 400 mg daily .
There did not appear to be any differences in the number of patients who withdrew due to adverse events or the number of patients with at least one adverse event in the eplerenone group compared to placebo .
Eplerenone 50 to 200 mg/day lowers blood pressure in people with primary hypertension by 9.21 mmHg systolic and 4.18 mmHg diastolic compared to placebo , with no difference of effect between doses of 50 mg/day to 200 mg/day .
A dose of 25 mg/day did not produce a statistically significant reduction in systolic or diastolic blood pressure and there is insufficient evidence for doses above 200 mg/day .
There is currently no available evidence to determine the effect of eplerenone on clinical ly meaningful outcomes such as mortality or morbidity in hypertensive patients .
The evidence available on side effects is insufficient and of low quality , which makes it impossible to draw conclusions about potential harm associated with eplerenone treatment in hypertensive patients