human
***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 Treatment of hypertension with diuretics , beta-blockers , or both leads to improved outcomes . It has been postulated that agents that inhibit the renin-angiotensin system confer benefit beyond the reduction of blood pressure alone . We compared the outcomes in older subjects with hypertension who were treated with angiotensin-converting-enzyme ( ACE ) inhibitors with the outcomes in those treated with diuretic agents . METHODS We conducted a prospect i ve , r and omized , open-label study with blinded assessment of end points in 6083 subjects with hypertension who were 65 to 84 years of age and received health care at 1594 family practice s. Subjects were followed for a median of 4.1 years , and the total numbers of cardiovascular events in the two treatment groups were compared with the use of multivariate proportional-hazards models . RESULTS At base line , the treatment groups were well matched in terms of age , sex , and blood pressure . By the end of the study , blood pressure had decreased to a similar extent in both groups ( a decrease of 26/12 mm Hg ) . There were 695 cardiovascular events or deaths from any cause in the ACE-inhibitor group ( 56.1 per 1000 patient-years ) and 736 cardiovascular events or deaths from any cause in the diuretic group ( 59.8 per 1000 patient-years ; the hazard ratio for a cardiovascular event or death with ACE-inhibitor treatment was 0.89 [ 95 percent confidence interval , 0.79 to 1.00 ] ; P=0.05 ) . Among male subjects , the hazard ratio was 0.83 ( 95 percent confidence interval , 0.71 to 0.97 ; P=0.02 ) ; among female subjects , the hazard ratio was 1.00 ( 95 percent confidence interval , 0.83 to 1.21 ; P=0.98 ) ; the P value for the interaction between sex and treatment-group assignment was 0.15 . The rates of nonfatal cardiovascular events and myocardial infa rct ions decreased with ACE-inhibitor treatment , whereas a similar number of strokes occurred in each group ( although there were more fatal strokes in the ACE-inhibitor group ) . CONCLUSIONS Initiation of antihypertensive treatment involving ACE inhibitors in older subjects , particularly men , appears to lead to better outcomes than treatment with diuretic agents , despite similar reductions of blood pressure Whether the strict control of blood pressure ( BP ) of patients with hypertension who are aged 85 years or older is beneficial is unclear . The Japan ’s Benidipine Research on Antihypertensive Effects in the Elderly study is a prospect i ve , observational 3-year study to evaluate the safety and effectiveness of treatment with a calcium channel blocker benidipine in 8897 hypertensive patients aged 65 years or older as a post-marketing surveillance . We examined the relationship between the achieved BP and cardiovascular events ( i.e. , stroke , myocardial infa rct ion , and heart failure ) in a subgroup of 415 patients aged 85 years or older ( mean age 88 years ) . BP decreased significantly from 165 ± 14/84 ± 10 mmHg to 130 ± 11/71 ± 10 mmHg during treatment in patients with a treated systolic BP ( SBP ) < 140 mmHg ( n = 230 ) and BP decreased significantly from 169 ± 16/86 ± 12 mmHg to 143 ± 13/75 ± 10 mmHg in those with a treated SBP ≥ 140 mmHg ( n = 185 ) . There was a nonsignificant trend toward a lower rate of cardiovascular events and higher rate of total death in patients with a treated SBP < 140 mmHg . On-treatment SBP ≥ 160 mmHg is tended to associate with a higher incidence of cardiovascular events . There was no significant difference in the incidence of adverse reactions between the controlled BP group ( 3.04 % ) and the less well controlled BP group ( 3.24 % ) . In conclusion , although this study was not powered for definitive conclusion , there was a nonsignificant trend toward a lower rate of cardiovascular events and higher total death in patients aged 85 years or older with a treated SBP < 140 mmHg Objective To assess if very elderly people with hypertension obtain early benefit from antihypertensive treatment . Design One year open label active treatment extension of r and omised controlled trial ( Hypertension in the Very Elderly Trial ( HYVET ) ) . Setting Hospital and general practice based centres mainly in eastern and western Europe , China , and Tunisia . Participants People on double blind treatment at the end of HYVET were eligible to enter the extension . Interventions Participants on active blood pressure lowering treatment continued taking active drug ; those on placebo were given active blood pressure lowering treatment . The treatment regimen was as used in the main trial — indapamide SR 1.5 mg ( plus perindopril 2 - 4 mg if required)—with the same target blood pressure of less than 150/80 mm Hg . Main outcome measures The primary outcome was all stroke ; other outcomes included total mortality , cardiovascular mortality , and cardiovascular events . Results Of 1882 people eligible for entry to the extension , 1712 ( 91 % ) agreed to participate . During the extension period , 1682 patient years were accrued . By six months , the difference in blood pressure between the two groups was 1.2/0.7 mm Hg . Comparing people previously treated with active drug and those previously on placebo , no significant differences were seen for stroke ( n=13 ; hazard ratio 1.92 , 95 % confidence interval 0.59 to 6.22 ) or cardiovascular events ( n=25 ; 0.78 , 0.36 to 1.72 ) . Differences were seen for total mortality ( 47 deaths ; hazard ratio 0.48 , 0.26 to 0.87 ; P=0.02 ) and cardiovascular mortality ( 11 deaths ; 0.19 , 0.04 to 0.87 ; P=0.03 ) . Conclusion Very elderly patients with hypertension may gain immediate benefit from treatment . Sustained differences in reductions of total mortality and cardiovascular mortality reinforce the benefits and support the need for early and long term treatment . Trial registration Clinical trials NCT00122811 Background The risks and benefits of treating hypertension in individuals older than 80 years are uncertain . A meta- analysis has suggested that a reduction in stroke events of 36 % may have to be balanced against a 14 % increase in total mortality . Objectives To report the results of the pilot study of the Hypertension in the Very Elderly Trial ( HYVET ) , which is in progress to address these issues . Methods The HYVET-Pilot was a multicentre international open pilot trial . In 10 European countries , 1283 patients older than 80 years and with a sustained blood pressure of 160–219/90–109 mmHg were allocated r and omly to one of three treatments : a diuretic-based regimen ( usually bendroflumethiazide ; n = 426 ) , an angiotensin-converting enzyme inhibitor regimen ( usually lisinopril ; n = 431 ) or no treatment ( n = 426 ) . The procedure permitted doses of the drug to be titrated and diltiazem slow-release to be added to active treatment . Target blood pressure was < 150/80 mmHg and mean follow-up was 13 months . Results In the combined actively treated groups , the reduction in stroke events relative hazard rate ( RHR ) was 0.47 [ 95 % confidence interval ( CI ) 0.24 to 0.93 ] and the reduction in stroke mortality RHR was 0.57 ( 95 % CI 0.25 to 1.32 ) . However , the estimate of total mortality supported the possibility of excess deaths with active treatment ( RHR 1.23 , 95 % CI 0.75 to 2.01 ) . Conclusions The preliminary results support the need for the continuing main HYVET trial . It is possible that treatment of 1000 patients for 1 year may reduce stroke events by 19 ( nine non-fatal ) , but may be associated with 20 extra non-stroke deaths The Combination Therapy of Hypertension to Prevent Cardiovascular Events ( COPE ) trial demonstrated that the calcium-channel blocker benidipine-based combination therapies with an angiotensin-receptor blocker ( ARB ) , a β-blocker , or a thiazide diuretic ( thiazide ) were similarly effective in preventing cardiovascular events and achieving the target blood pressure ( BP ; < 140/90 mm Hg ) . We further evaluated the efficacy and safety of these combination therapies in older ( ⩾65 years ) and younger ( < 65 years ) hypertensive patients . In this sub- analysis of the COPE trial 3293 patients ( 1533⩾65 years old and 1760 < 65 years old ) were r and omly assigned to receive benidipine-based therapy with an ARB , a β-blocker or a thiazide . In each group , the average BP did not differ among the three treatment groups . The incidence of the primary cardiovascular composite end point in the older group was higher than in the younger group ( 12.7 vs. 8.3 per 1000 person-years , P=0.023 ) . The primary composite cardiovascular end point , achievement ( % ) of target BP , and cardiovascular hard composite end points were similar among the three treatment groups . However , the hazard ratios and 95 % confidence intervals in older patients were 2.74 ( 1.08–6.96 ; β-blocker vs. thiazide , P=0.022 ) for fatal and non-fatal stroke , and 2.47 ( 1.03–5.91 ; β-blocker vs. ARB , P=0.043 ) for new-onset diabetes . Thus , benidipine combined with an ARB , a β-blocker , or a thiazide was similarly effective in preventing cardiovascular events and achieving the target BP in both older and younger hypertensive patients . Further studies will be necessary to evaluate the usefulness of benidipine combined with a β-blocker in terms of the incidence of stroke and new-onset diabetes in older patients In this prospect i ve , r and omized , open-label , blinded end point study , we aim ed to establish whether strict blood pressure control ( < 140 mm Hg ) is superior to moderate blood pressure control ( ≥140 mm Hg to < 150 mm Hg ) in reducing cardiovascular mortality and morbidity in elderly patients with isolated systolic hypertension . We divided 3260 patients aged 70 to 84 years with isolated systolic hypertension ( sitting blood pressure 160 to 199 mm Hg ) into 2 groups , according to strict or moderate blood pressure treatment . A composite of cardiovascular events was evaluated for ≥2 years . The  strict control ( 1545 patients ) and moderate control ( 1534 patients ) groups were well matched ( mean age : 76.1 years ; mean blood pressure : 169.5/81.5 mm Hg ) . Median follow-up was 3.07 years . At 3 years , blood pressure reached 136.6/74.8 mm Hg and 142.0/76.5 mm Hg , respectively . The blood pressure difference between the 2 groups was 5.4/1.7 mm Hg . The overall rate of the primary composite end point was 10.6 per 1000 patient-years in the strict control group and 12.0 per 1000 patient-years in the moderate control group ( hazard ratio : 0.89 ; [ 95 % CI : 0.60 to 1.34 ] ; P=0.38 ) . In summary , blood pressure targets of < 140 mm Hg are safely achievable in relatively healthy patients ≥70 years of age with isolated systolic hypertension , although our trial was underpowered to definitively determine whether strict control was superior to less stringent blood pressure targets A r and omized , double-blind , active-controlled , multicenter trial assigned 32,804 participants aged 55 years and older with hypertension and ≥ 1 other coronary heart disease risk factors to receive chlorthalidone ( n=15,002 ) , amlodipine ( n=8898 ) , or lisinopril ( n=8904 ) for 4 to 8 years , when double-blinded therapy was discontinued . Passive surveillance continued for a total follow-up of 8 to 13 years using national administrative data bases to ascertain deaths and hospitalizations . During the post-trial period , fatal outcomes and nonfatal outcomes were available for 98 % and 65 % of participants , respectively , due to lack of access to administrative data bases for the remainder . This paper assesses whether mortality and morbidity differences persisted or new differences developed during the extended follow-up . Primary outcome was cardiovascular mortality and secondary outcomes were mortality , stroke , coronary heart disease , heart failure , cardiovascular disease , and end-stage renal disease . For the post-trial period , 
    Output:
    
agent
Strict control [ systolic BP ( SBP ) < 140 mmHg ] was not consistently better than mild control ( SBP < 150 mmHg ) for adults aged ≥65 years .
Mild SBP control benefitted subjects in all age ranges over 65 years .
Conclusions In this review , older adults with hypertension had decreased cardiovascular morbidity and mortality  with antihypertensives compared with no treatment .
Strict control was not consistently better than mild control in older adults .
The current evidence is insufficient to determine the safest , most beneficial hypertension regimen in older adults
***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 Treatment of hypertension with diuretics , beta-blockers , or both leads to improved outcomes . It has been postulated that agents that inhibit the renin-angiotensin system confer benefit beyond the reduction of blood pressure alone . We compared the outcomes in older subjects with hypertension who were treated with angiotensin-converting-enzyme ( ACE ) inhibitors with the outcomes in those treated with diuretic agents . METHODS We conducted a prospect i ve , r and omized , open-label study with blinded assessment of end points in 6083 subjects with hypertension who were 65 to 84 years of age and received health care at 1594 family practice s. Subjects were followed for a median of 4.1 years , and the total numbers of cardiovascular events in the two treatment groups were compared with the use of multivariate proportional-hazards models . RESULTS At base line , the treatment groups were well matched in terms of age , sex , and blood pressure . By the end of the study , blood pressure had decreased to a similar extent in both groups ( a decrease of 26/12 mm Hg ) . There were 695 cardiovascular events or deaths from any cause in the ACE-inhibitor group ( 56.1 per 1000 patient-years ) and 736 cardiovascular events or deaths from any cause in the diuretic group ( 59.8 per 1000 patient-years ; the hazard ratio for a cardiovascular event or death with ACE-inhibitor treatment was 0.89 [ 95 percent confidence interval , 0.79 to 1.00 ] ; P=0.05 ) . Among male subjects , the hazard ratio was 0.83 ( 95 percent confidence interval , 0.71 to 0.97 ; P=0.02 ) ; among female subjects , the hazard ratio was 1.00 ( 95 percent confidence interval , 0.83 to 1.21 ; P=0.98 ) ; the P value for the interaction between sex and treatment-group assignment was 0.15 . The rates of nonfatal cardiovascular events and myocardial infa rct ions decreased with ACE-inhibitor treatment , whereas a similar number of strokes occurred in each group ( although there were more fatal strokes in the ACE-inhibitor group ) . CONCLUSIONS Initiation of antihypertensive treatment involving ACE inhibitors in older subjects , particularly men , appears to lead to better outcomes than treatment with diuretic agents , despite similar reductions of blood pressure Whether the strict control of blood pressure ( BP ) of patients with hypertension who are aged 85 years or older is beneficial is unclear . The Japan ’s Benidipine Research on Antihypertensive Effects in the Elderly study is a prospect i ve , observational 3-year study to evaluate the safety and effectiveness of treatment with a calcium channel blocker benidipine in 8897 hypertensive patients aged 65 years or older as a post-marketing surveillance . We examined the relationship between the achieved BP and cardiovascular events ( i.e. , stroke , myocardial infa rct ion , and heart failure ) in a subgroup of 415 patients aged 85 years or older ( mean age 88 years ) . BP decreased significantly from 165 ± 14/84 ± 10 mmHg to 130 ± 11/71 ± 10 mmHg during treatment in patients with a treated systolic BP ( SBP ) < 140 mmHg ( n = 230 ) and BP decreased significantly from 169 ± 16/86 ± 12 mmHg to 143 ± 13/75 ± 10 mmHg in those with a treated SBP ≥ 140 mmHg ( n = 185 ) . There was a nonsignificant trend toward a lower rate of cardiovascular events and higher rate of total death in patients with a treated SBP < 140 mmHg . On-treatment SBP ≥ 160 mmHg is tended to associate with a higher incidence of cardiovascular events . There was no significant difference in the incidence of adverse reactions between the controlled BP group ( 3.04 % ) and the less well controlled BP group ( 3.24 % ) . In conclusion , although this study was not powered for definitive conclusion , there was a nonsignificant trend toward a lower rate of cardiovascular events and higher total death in patients aged 85 years or older with a treated SBP < 140 mmHg Objective To assess if very elderly people with hypertension obtain early benefit from antihypertensive treatment . Design One year open label active treatment extension of r and omised controlled trial ( Hypertension in the Very Elderly Trial ( HYVET ) ) . Setting Hospital and general practice based centres mainly in eastern and western Europe , China , and Tunisia . Participants People on double blind treatment at the end of HYVET were eligible to enter the extension . Interventions Participants on active blood pressure lowering treatment continued taking active drug ; those on placebo were given active blood pressure lowering treatment . The treatment regimen was as used in the main trial — indapamide SR 1.5 mg ( plus perindopril 2 - 4 mg if required)—with the same target blood pressure of less than 150/80 mm Hg . Main outcome measures The primary outcome was all stroke ; other outcomes included total mortality , cardiovascular mortality , and cardiovascular events . Results Of 1882 people eligible for entry to the extension , 1712 ( 91 % ) agreed to participate . During the extension period , 1682 patient years were accrued . By six months , the difference in blood pressure between the two groups was 1.2/0.7 mm Hg . Comparing people previously treated with active drug and those previously on placebo , no significant differences were seen for stroke ( n=13 ; hazard ratio 1.92 , 95 % confidence interval 0.59 to 6.22 ) or cardiovascular events ( n=25 ; 0.78 , 0.36 to 1.72 ) . Differences were seen for total mortality ( 47 deaths ; hazard ratio 0.48 , 0.26 to 0.87 ; P=0.02 ) and cardiovascular mortality ( 11 deaths ; 0.19 , 0.04 to 0.87 ; P=0.03 ) . Conclusion Very elderly patients with hypertension may gain immediate benefit from treatment . Sustained differences in reductions of total mortality and cardiovascular mortality reinforce the benefits and support the need for early and long term treatment . Trial registration Clinical trials NCT00122811 Background The risks and benefits of treating hypertension in individuals older than 80 years are uncertain . A meta- analysis has suggested that a reduction in stroke events of 36 % may have to be balanced against a 14 % increase in total mortality . Objectives To report the results of the pilot study of the Hypertension in the Very Elderly Trial ( HYVET ) , which is in progress to address these issues . Methods The HYVET-Pilot was a multicentre international open pilot trial . In 10 European countries , 1283 patients older than 80 years and with a sustained blood pressure of 160–219/90–109 mmHg were allocated r and omly to one of three treatments : a diuretic-based regimen ( usually bendroflumethiazide ; n = 426 ) , an angiotensin-converting enzyme inhibitor regimen ( usually lisinopril ; n = 431 ) or no treatment ( n = 426 ) . The procedure permitted doses of the drug to be titrated and diltiazem slow-release to be added to active treatment . Target blood pressure was < 150/80 mmHg and mean follow-up was 13 months . Results In the combined actively treated groups , the reduction in stroke events relative hazard rate ( RHR ) was 0.47 [ 95 % confidence interval ( CI ) 0.24 to 0.93 ] and the reduction in stroke mortality RHR was 0.57 ( 95 % CI 0.25 to 1.32 ) . However , the estimate of total mortality supported the possibility of excess deaths with active treatment ( RHR 1.23 , 95 % CI 0.75 to 2.01 ) . Conclusions The preliminary results support the need for the continuing main HYVET trial . It is possible that treatment of 1000 patients for 1 year may reduce stroke events by 19 ( nine non-fatal ) , but may be associated with 20 extra non-stroke deaths The Combination Therapy of Hypertension to Prevent Cardiovascular Events ( COPE ) trial demonstrated that the calcium-channel blocker benidipine-based combination therapies with an angiotensin-receptor blocker ( ARB ) , a β-blocker , or a thiazide diuretic ( thiazide ) were similarly effective in preventing cardiovascular events and achieving the target blood pressure ( BP ; < 140/90 mm Hg ) . We further evaluated the efficacy and safety of these combination therapies in older ( ⩾65 years ) and younger ( < 65 years ) hypertensive patients . In this sub- analysis of the COPE trial 3293 patients ( 1533⩾65 years old and 1760 < 65 years old ) were r and omly assigned to receive benidipine-based therapy with an ARB , a β-blocker or a thiazide . In each group , the average BP did not differ among the three treatment groups . The incidence of the primary cardiovascular composite end point in the older group was higher than in the younger group ( 12.7 vs. 8.3 per 1000 person-years , P=0.023 ) . The primary composite cardiovascular end point , achievement ( % ) of target BP , and cardiovascular hard composite end points were similar among the three treatment groups . However , the hazard ratios and 95 % confidence intervals in older patients were 2.74 ( 1.08–6.96 ; β-blocker vs. thiazide , P=0.022 ) for fatal and non-fatal stroke , and 2.47 ( 1.03–5.91 ; β-blocker vs. ARB , P=0.043 ) for new-onset diabetes . Thus , benidipine combined with an ARB , a β-blocker , or a thiazide was similarly effective in preventing cardiovascular events and achieving the target BP in both older and younger hypertensive patients . Further studies will be necessary to evaluate the usefulness of benidipine combined with a β-blocker in terms of the incidence of stroke and new-onset diabetes in older patients In this prospect i ve , r and omized , open-label , blinded end point study , we aim ed to establish whether strict blood pressure control ( < 140 mm Hg ) is superior to moderate blood pressure control ( ≥140 mm Hg to < 150 mm Hg ) in reducing cardiovascular mortality and morbidity in elderly patients with isolated systolic hypertension . We divided 3260 patients aged 70 to 84 years with isolated systolic hypertension ( sitting blood pressure 160 to 199 mm Hg ) into 2 groups , according to strict or moderate blood pressure treatment . A composite of cardiovascular events was evaluated for ≥2 years . The  strict control ( 1545 patients ) and moderate control ( 1534 patients ) groups were well matched ( mean age : 76.1 years ; mean blood pressure : 169.5/81.5 mm Hg ) . Median follow-up was 3.07 years . At 3 years , blood pressure reached 136.6/74.8 mm Hg and 142.0/76.5 mm Hg , respectively . The blood pressure difference between the 2 groups was 5.4/1.7 mm Hg . The overall rate of the primary composite end point was 10.6 per 1000 patient-years in the strict control group and 12.0 per 1000 patient-years in the moderate control group ( hazard ratio : 0.89 ; [ 95 % CI : 0.60 to 1.34 ] ; P=0.38 ) . In summary , blood pressure targets of < 140 mm Hg are safely achievable in relatively healthy patients ≥70 years of age with isolated systolic hypertension , although our trial was underpowered to definitively determine whether strict control was superior to less stringent blood pressure targets A r and omized , double-blind , active-controlled , multicenter trial assigned 32,804 participants aged 55 years and older with hypertension and ≥ 1 other coronary heart disease risk factors to receive chlorthalidone ( n=15,002 ) , amlodipine ( n=8898 ) , or lisinopril ( n=8904 ) for 4 to 8 years , when double-blinded therapy was discontinued . Passive surveillance continued for a total follow-up of 8 to 13 years using national administrative data bases to ascertain deaths and hospitalizations . During the post-trial period , fatal outcomes and nonfatal outcomes were available for 98 % and 65 % of participants , respectively , due to lack of access to administrative data bases for the remainder . This paper assesses whether mortality and morbidity differences persisted or new differences developed during the extended follow-up . Primary outcome was cardiovascular mortality and secondary outcomes were mortality , stroke , coronary heart disease , heart failure , cardiovascular disease , and end-stage renal disease . For the post-trial period , 
    Output:
    