***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: Spironolactone is recommended as fourth-line therapy for essential hypertension despite few supporting data for this indication . We evaluated the effect among 1411 participants in the Anglo-Sc and inavian Cardiac Outcomes Trial-Blood Pressure Lowering Arm who received spironolactone mainly as a fourth-line antihypertensive agent for uncontrolled blood pressure and who had valid BP measurements before and during spironolactone treatment . Among those who received spironolactone , the mean age was 63 years ( SD : ±8 years ) , 77 % were men , and 40 % had diabetes .  Spironolactone was initiated a median of 3.2 years ( interquartile range : 2.0 to 4.4 years ) after r and omization and added to a mean of 2.9 ( SD : ±0.9 ) other antihypertensive drugs . The median duration of spironolactone  treatment was 1.3 years ( interquartile range : 0.6 to 2.6 years ) . The median dose of spironolactone was 25 mg ( interquartile range : 25 to 50 mg ) at both the start and end of the observation period . During spironolactone therapy , mean blood pressure fell from 156.9/85.3 mm Hg ( SD : ±18.0/11.5 mm Hg ) by 21.9/9.5 mm Hg ( 95 % CI : 20.8 to 23.0/9.0 to 10.1 mm Hg ; P<0.001 ) ; the BP reduction was largely unaffected by age , sex , smoking , and diabetic status . Spironolactone was generally well tolerated ; 6 % of participants discontinued the drug because of adverse effects . The most frequent adverse events were gynecomastia or breast discomfort and biochemical abnormalities ( principally hyperkaliemia ) , which were recorded as adverse events in 6 % and 2 % of participants , respectively . In conclusion , spironolactone  effectively lowers blood pressure in patients with hypertension uncontrolled by a mean of ≈3 other drugs . Although nonr and omized and not placebo controlled , these data support the use of spironolactone in uncontrolled hypertension Abstract —Recent reports suggesting that the prevalence of primary hyperaldosteronism may be higher than historically thought have relied on an elevated plasma aldosterone concentration/plasma renin activity ratio to either diagnose or identify subjects at high risk of having primary hyperaldosteronism and have not included suppression testing of all evaluated subjects . In this prospect i ve study of 88 consecutive patients referred to a university clinic for resistant hypertension , we determined the 24-hour urinary aldosterone excretion during high dietary salt ingestion , baseline plasma renin activity , and plasma aldosterone in all subjects . Primary hyperaldosteronism was confirmed if plasma renin activity was < 1.0 ng/mL per hour and urinary aldosterone was > 12 & mgr;g/24-hour during high urinary sodium excretion ( > 200 mEq/24-hour ) . Eighteen subjects ( 20 % ) were confirmed to have primary hyperaldosteronism . The prevalence of hyperaldosteronism was similar in black and white subjects . Of the 14 subjects with confirmed hyperaldosteronism who have been treated with spironolactone , all have manifested a significant reduction in blood pressure . In this population , an elevated plasma aldosterone/plasma renin activity ratio ( > 20 ) had a sensitivity of 89 % and a specificity of 71 % with a corresponding positive predictive value of 44 % and a negative predictive value of 96 % . These data provide strong evidence that hyperaldosteronism is a common cause of resistant hypertension in black and white subjects . The accuracy of these results is strengthened by having done suppression testing of all evaluated subjects 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 Obstructive sleep apnoea ( OSA ) and hyperaldosteronism are very common in subjects with resistant hypertension . We hypothesized that aldosterone-mediated chronic fluid retention may influence OSA severity in patients with resistant hypertension . We tested this in an open-label evaluation by assessing the changes in the severity of OSA in patients with resistant hypertension after treatment with spironolactone . Subjects with resistant hypertension ( clinical blood pressure ( BP ) ⩾140/90 mm Hg on ⩾3 antihypertensive medications , including a thiazide diuretic and OSA ( defined as an apnoea – hypopnoea index ( AHI ) ⩾15 ) had full diagnostic , polysomnography before and 8 weeks after spironolactone ( 25–50 mg a day ) was added to their ongoing antihypertensive therapy . In all , 12 patients ( mean age 56 years and body mass index 36.8 kg m–2 ) were evaluated . After treatment with spironolactone , the AHI ( 39.8±19.5 vs 22.0±6.8 events/h ; P<0.05 ) and hypoxic index ( 13.6±10.8 vs 6.7±6.6 events/h ; P<0.05 ) , weight and clinic and ambulatory BP were significantly reduced . Plasma renin activity ( PRA ) and serum creatinine were significantly higher . This study provides preliminary evidence that treatment with a mineralocorticoid receptor antagonist  substantially reduces the severity of OSA . If confirmed in a r and omized assessment , it will support aldosterone-mediated chronic fluid retention as an important mediator of OSA severity in patients with resistant hypertension The role of spironolactone in resistant hypertension management is unclear . The aim of this prospect i ve trial was to evaluate the antihypertensive effect of spironolactone in patients with true resistant hypertension diagnosed by ambulatory blood pressure monitoring . A total of 175 patients had clinical and complementary exams obtained at baseline and received spironolactone in doses of 25 to 100 mg/d . A second ambulatory blood pressure monitoring was performed after a median interval of 7 months . Paired Student t test was used to assess differences in blood pressure before and during spironolactone administration , and multivariate analysis adjusted for age , sex , and number of antihypertensive drugs to assess the predictors of blood pressure fall . There were mean reductions of 16 and 9 mm Hg , respectively , in 24-hour systolic and diastolic blood pressures ( 95 % CIs : 13 to 18 and 7 to 10 mm Hg ; P<0.001 ) . Office systolic blood pressure and diastolic blood pressure also decreased ( 14 and 7 mm Hg ) . Controlled ambulatory blood pressure was reached in 48 % of patients . Factors associated with better response were higher waist circumference , lower aortic pulse wave velocity , and lower serum potassium . No association with plasma aldosterone or aldosterone : renin ratio was found . Adverse effects were observed in 13 patients ( 7.4 % ) . A third ambulatory blood pressure monitoring performed in 78 patients after a median of 15 months confirmed the persistence of the spironolactone effect . In conclusion , spironolactone administration to true resistant hypertensive patients is safe and effective in decreasing blood pressure , especially in those with abdominal obesity and lower arterial stiffness . Its addition to an antihypertensive regimen as the fourth or fifth drug is recommended Background : Aldosterone antagonists have proven efficacy for management of resistant hypertension and proteinuria reduction ; however , they are not widely used due to risk of hyperkalemia . This study assesses the risk factors for hyperkalemia in patients with chronic kidney disease ( CKD ) and resistant hypertension whose blood pressure ( BP ) is reduced to a guideline goal . Methods : This is a two-center study conducted in university-based hypertension clinics directed by clinical hypertension specialists . Forty-six patients with resistant hypertension and stages 2 or 3 CKD ( mean estimated glomerular filtration rate ( eGFR ) 56.5 ± 16.2 ml/min/1.73 m2 ) were evaluated for safety and efficacy of aldosterone blockade added to preexisting BP-lowering regimens . All patients were on three mechanistically complementary antihypertensive agents including a diuretic and a renin-angiotensin system blocker . Patients were evaluated after a median of 45 treatment days . The primary endpoint was change in systolic BP . Secondary endpoints included change in serum potassium , creatinine , eGFR , diastolic BP and tolerability . Results : The mean age of the patients studied was 64.9 ± 10.7 years , all were obese and 86 % had type 2 diabetes , with 82 % being African-American . Addition of aldosterone antagonism yielded a further mean reduction in systolic BP of 14.7 ± 5.1 mm Hg ( p = 0.001 ) . Females with BMI > 30 and those with a baseline systolic BP > 160 mm Hg were more likely to have a greater BP reduction to aldosterone antagonism . In total , 39 % of the patients had a > 30 % decrease in eGFR when the BP goal was achieved . The mean increase in serum potassium was 0.4 mEq/l above baseline ( p = 0.001 ) , with 17.3 % manifesting hyperkalemia , i.e. serum potassium > 5.5 mEq/l . Predictors of hyperkalemia included a baseline eGFR of ≤45 ml/min/1.73 m2 in whom serum potassium was > 4.5 mEq/l on appropriately dosed diuretics . Contributing risks in this subgroup included a systolic BP reduction of > 15 mm Hg associated with an eGFR fall of > 30 % . Conclusion : Aldosterone antagonism is effective and safe for achieving a BP goal among people with diabetic nephropathy when added to a triple antihypertensive regimen that includes a blocker of the renin-angiotensin system and an appropriately selected and dosed diuretic . Caution is advised when using aldosterone blockade for BP control in people with advanced stage 3 nephropathy with a serum potassium of > 4.5 mEq/l for safety reasons To determine the antihypertensive benefit of adding low dose sprinolactone to multi-drug regimens that included a diuretic , a calcium channel blocker and angiotensin-converting enzyme inhibitor or angiotensin receptor blocker in patients with moderately severe chronic kidney disease ( CKD ) [ glomerular filtration rate ( GFR ) 25 - 50 mL/min ] and resistant hyper-tension , we studied 41 patients r and omly divided into two groups : group 1 : patients who received  placebo as spironolactone  and group 2 : patients who received spironolactone 25 - 50 mg/day . The patients were evaluated during follow-up at the 6th and 12th weeks . The mean decrease in systolic and diastolic blood pressure after 6 weeks of spironolactone was 33 ± 8 and 13 ± 2 mmHg , respectively , and it was maintained after 12 weeks of spironolactone wherein the values were 36 ± 10 and 12 ± 2 mmHg , respectively , while there was no change in the blood pressure in the control group . Hyperkalemia ( serum potassium > 5.5 meq/L ) occurred in one subject in the spironolactone group . We conclude that low- 
    Output:
    
Subgroup analysis showed that the systolic BP change was more pronounced in patients with baseline systolic BP > 150 mm Hg ( weighted mean difference ( WMD ) , −23.1 mm Hg ) than in patients with ⩽150 mm Hg ( WMD , −15.4 mm Hg ) ( between groups P<0.001 ) , suggesting that the baseline systolic BP was a predictor of the BP response to AA treatment .
Furthermore , AA demonstrated a mild increase in serum potassium and creatinine ( for both , P<0.001 ) .
The findings suggest that AA as an add-on therapy was effective for lowering systolic and diastolic BP in patients with RH