***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: Although the benefits of antihypertensive treatment in " young " elderly ( under 70 years ) hypertensive patients are well established , the value of treatment in older patients ( 70 - 84 years ) is less clear . The Swedish Trial in Old Patients with Hypertension ( STOP-Hypertension ) was a prospect i ve , r and omised , double-blind , intervention study set up to compare the effects of active antihypertensive therapy ( three beta-blockers and one diuretic ) and placebo on the frequency of fatal and non-fatal stroke and myocardial infa rct ion and other cardiovascular death in hypertensive Swedish men and women aged 70 - 84 years . We recruited 1627 patients at 116 health centres throughout Sweden , who were willing to participate , and who met the entry criteria of three separate recordings during a 1-month placebo run-in period of systolic blood pressure between 180 and 230 mm Hg with a diastolic pressure of at least 90 mm Hg , or a diastolic pressure between 105 and 120 mm Hg irrespective of the systolic pressure . The total duration of the study was 65 months and the average time in the study was 25 months . 812 patients were r and omly allocated active treatment and 815 placebo . The mean difference in supine blood pressure between the active treatment and placebo groups at the last follow-up before an endpoint , death , or study termination was 19.5/8.1 mm Hg . Compared with placebo , active treatment significantly reduced the number of primary endpoints ( 94 vs 58 ; p = 0.0031 ) and stroke morbidity and mortality ( 53 vs 29 ; p = 0.0081 ) . Although we did not set out to study an effect on total mortality , we also noted a significantly reduced number of deaths in the active treatment group ( 63 vs 36 ; p = 0.0079 ) . The benefits of treatment were discernible up to age 84 years . We conclude that antihypertensive treatment in hypertensive men and women aged 70 - 84 confers highly significant and clinical ly relevant reductions in cardiovascular morbidity and mortality as well as in total mortality Neuroendocrine activation is known to occur in patients with congestive heart failure , but there is uncertainty as to whether this occurs before or after the presence of overt symptoms . In the Studies of Left Ventricular Dysfunction ( SOLVD ) , a multicenter study of patients with ejection fractions of 35 % or less , we compared baseline plasma norepinephrine , plasma renin activity , plasma atrial natriuretic factor , and plasma arginine vasopressin in 56 control subjects , 151 patients with left ventricular dysfunction ( no overt heart failure ) , and 81 patients with overt heart failure before r and omization .  Median values for plasma norepinephrine ( p = 0.0001 ) , plasma atrial natriuretic factor ( p less than 0.0001 ) , plasma arginine vasopressin ( p = 0.006 ) , and plasma renin activity ( p = 0.03 ) were significantly higher in patients with left ventricular dysfunction than in normal control subjects . Neuroendocrine values were highest in patients with overt heart failure . Plasma renin activity was normal in patients with left ventricular dysfunction without heart failure who were not receiving diuretics and was significantly increased ( p less than 0.05 ) in patients on diuretic therapy . We conclude that neuroendocrine activation occurs in patients with left ventricular dysfunction and no heart failure .  Neuroendocrine activation is further increased as overt heart failure ensues and diuretics are added to therapy The diuretic and clinical efficacy and safety of piretanide , a new high‐ceiling loop diuretic , was determined in patients with mild to moderately severe congestive heart failure .  Piretanide  ( n = 20 ) administered orally in a daily dosage of up to 24 mg was compared with placebo ( n = 18 ) for 28 days , using a double‐blind , r and omized , parallel design . Patients were hospitalized during the first 5 days of the study when dosage titration was established and 24‐hour fractionated urine collection s were obtained .  Piretanide  caused significant diuresis for 3 hours after ingestion with a natriuretic response noted for up to 6 hours . While occasional kaliuretic response was noted , it did not significantly increase 24‐hour urinary potassium excretion . Only one patient treated with the highest allowed dose of piretanide developed mild hypokalemia . An improvement in New York Heart Association functional class status was noted after piretanide therapy . In contrast , patients who received placebo exhibited no significant improvement . BUN increased in nine piretanide‐treated patients ; two were discontinued from the study because of progressive azotemia . However , there was no significant increase in serum creatinine levels . Other blood , physical , ECG , and audiometrie examinations also revealed no significant abnormalities . The study suggests that oral piretanide is a relatively safe and effective diuretic for treating congestive heart failure with a potential advantage of having potassium‐sparing properties Background Ten chronic heart failure patients were studied on three occasions in r and omized double-blind fashion to compare the acute hemodynamic , neurohormonal , and renal sodium-h and ling responses to 1 mg captopril versus 25 mg captopril , both in the absence of loop diuretic therapy and during furosemide-stimulated natriuresis . Methods and Results Compared with placebo , 1 mg captopril caused nonsignificant decreases in mean arterial pressure and circulating angiotensin II level and had no effect on glomerular filtration rate as determined by 51Cr-EDTA elimination . Captopril ( 25 mg ) produced marked suppression of serum angiotensin II with or without oral furosemide ( both p < 0.002 ) , a marked decrease in mean arterial pressure ( p < 0.0001 ) that was accentuated by furosemide ( p < 0.00001 ) , and a decrease in glomerular filtration rate ( p = 0.0007 ) . No difference from placebo in renal sodium excretion was noted with either 1 or 25 mg captopril in the absence of furosemide . In contrast , while 25 mg captopril caused slight attenuation of the natriuretic response to furosemide , 1 mg captopril significantly enhanced furosemideinduced natriuresis ( p < 0.05 ) . No correlation was found in our patients between the natriuretic effect of furosemide and either absolute mean arterial pressure or change in mean arterial pressure during the furosemide phase of each study session . This suggests that blood pressure is not the important factor mediating the divergent renal responses to furosemide of the two captopril dosage regimens . Conclusions We propose that in the face of furosemide-induced postglomerular vasodilatation in chronic heart failure , captopril at a starting dose of 1 mg ( but not 25 mg ) preserves enough circulating angiotensin II to maintain efferent arteriolar tone and thus glomerular filtration , while off setting the antinatriuretic renal tubular effects of angiotensin II BACKGROUND The RALES study showed that spironolactone , added to conventional therapy for chronic heart failure , dramatically reduced mortality . We tested the hypothesis that this benefit was partially due to improvement in endothelial function and /or to amplified suppression of the vascular renin-angiotensin axis . METHODS AND RESULTS We performed a r and omized , placebo-controlled , double-blind crossover study on 10 patients with NYHA class II to III chronic heart failure on st and ard diuretic/ACE inhibitor therapy , comparing 50 mg/d spironolactone ( 1 month ) versus placebo .  Forearm vasculature endothelial function was assessed by bilateral forearm venous occlusion plethysmography using acetylcholine and N-monomethyl-L-arginine ( L-NMMA ) , with sodium nitroprusside as a control vasodilator . Also , vascular ACE activity was assessed by use of angiotensin ( Ang ) I , with Ang II as a control vasoconstrictor . Spironolactone significantly increased the forearm blood flow response to acetylcholine ( percentage change in forearm blood flow [ mean+/-SEM ] , 177+/-29 % versus 95+/-20 % , spironolactone versus placebo ; P<0.001 ) , with an associated increase in vasoconstriction due to L-NMMA ( -35+/-6 % versus -18+/-4 % ; P<0.05 ) . The Ang I response was also significantly reduced with spironolactone ( P<0.05 ) , with Ang II responses unaltered . CONCLUSIONS Spironolactone improves endothelial dysfunction , increases NO bioactivity , and inhibits vascular Ang I/Ang II conversion in patients with heart failure , providing novel mechanisms for its beneficial effect on cardiovascular mortality Background — In patients with chronic heart failure ( CHF ) , a β-blocker is generally added to a regimen containing an angiotensin-converting-enzyme ( ACE ) inhibitor . It is unknown whether β-blockade as initial therapy may be as useful . Methods and Results — We r and omized 1010 patients with mild to moderate CHF and left ventricular ejection fraction ≤35 % , who were not receiving ACE inhibitor , β-blocker , or angiotensin receptor blocker therapy , to open-label monotherapy with either bisoprolol  ( target dose 10 mg QD ; n=505 ) or enalapril ( target dose 10 mg BID ; n=505 ) for 6 months , followed by their combination for 6 to 24 months . The 2 strategies were blindly compared with regard to the combined primary end point of all-cause mortality or hospitalization and with regard to each of these end point components individually . Bisoprolol-first treatment was noninferior to enalapril-first treatment if the upper limit of the 95 % confidence interval ( CI ) for the absolute between-group difference was < 5 % , corresponding to a hazard ratio ( HR ) of 1.17 . In the intention-to-treat sample , the primary end point occurred in 178 patients allocated to bisoprolol-first treatment versus 186 allocated to enalapril-first treatment ( absolute difference −1.6 % , 95 % CI −7.6 to 4.4 % , HR 0.94 ; 95 % CI 0.77 to 1.16 ) . In the per- protocol sample , 163 patients allocated to bisoprolol-first treatment had a primary end point , versus 165 allocated to enalapril-first treatment ( absolute difference −0.7 % , 95 % CI −6.6 to 5.1 % , HR 0.97 ; 95 % CI 0.78 to 1.21 ) . With bisoprolol-first treatment , 65 patients died , versus 73 with enalapril-first treatment ( HR 0.88 ; 95 % CI 0.63 to 1.22 ) , and 151 versus 157 patients were hospitalized ( HR 0.95 ; 95 % CI 0.76 to 1.19 ) . Conclusion — Although noninferiority of bisoprolol-first versus enalapril-first treatment was not proven in the per- protocol analysis , our results indicate that it may be as safe and efficacious to initiate treatment for CHF with bisoprolol as with enalapril AIMS It is reported that one third of patients with heart failure have normal left ventricular systolic function , and may or may not have left ventricular diastolic dysfunction . We sought to define the prevalence of left ventricular diastolic filling abnormalities in a large unselected group of patients , unlike the diagnosis by exclusion in the small highly selected groups of patients studied previously . METHODS AND RESULTS Patients were referred by general practitioners to an open-access echocardiography service for assessment of possible heart failure .  Echocardiography included a Doppler study of transmitral flow at the tips of the mitral leaflets and calculation of an E/A ratio . Of 534 patients referred and assessed , 371 patients had normal systolic function  and a  measurable E/A ratio . These were compared with age-adjusted reference ranges to give 9 above the reference range and 19 below . This is only 10 more than would be expected if our patients were normal . In the same group of patients we found 96 cases of left ventricular systolic dysfunction , or 52 amongst the 423 with a measurable E/A ratio . CONCLUSION Either left ventricular diastolic filling abnormalities are very much less common than previously supposed or the E/A ratio is almost useless for their detection OBJECTIVES We sought to determine whether non-potassium-sparing diuretics ( PSDs ) in the absence of a PSD may result in  progressive heart failure ( HF ) . BACKGROUND Angiotensin-converting enzyme ( ACE ) inhibitors incompletely suppress ACE activity in HF patients . Furthermore , non-PSDs are activators of aldosterone secretion . We reasoned that non-PSDs , in the absence of a PSD , might result in progressive HF . METHODS In the 6,797 patients in the Studies Of Left Ventricular Dysfunction ( SOLVD ) , we compared the risk of hospitalization for , or death from , HF 
    Output:
    
The available data from several small trials show that in patients with chronic heart failure , conventional diuretics appear to reduce the risk of death and worsening heart failure compared to placebo .
Compared to active control , diuretics appear to improve exercise capacity