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: This study investigated the differences in the effect of an angiotensin converting enzyme inhibitor ( ACEI ) compared with an angiotensin receptor blocker ( ARB ) on blood pressure ( BP ) and pulse pressure ( PP ) measured in the clinic ( CBP and CPP , respectively ) , at home ( HBP , HPP ) and with ambulatory monitoring ( ABP , APP ) . Twenty-seven hypertensive patients were r and omised to receive lisinopril ( 20 mg ) or losartan ( 50 mg ) for 5 weeks , and were subsequently crossed-over to the alternative treatment for a second 5-week period . Measurements of CBP , 24-h ABP and 5-days HBP were performed before r and omisation and at the end of each treatment period . All measurement methods showed that lisinopril was more effective than losartan in reducing BP . However , the difference between the two drugs was demonstrated with greater precision using HBP ( P<0.001 ) than 24-h ABP ( P<0.01 ) , whereas the poorest precision for demonstrating this difference was provided by CBP ( P<0.05 ) . Lisinopril was also found more effective than losartan in reducing HPP ( P=0.01 ) and 24-h APP ( P=0.03 ) whereas no such a difference was detected using measurements of CPP . It was concluded that the antihypertensive drugs may differ in their effects not only on BP , but also on PP . HBP monitoring appears to be as reliable as 24-h ABP monitoring in detecting differences in the effect of drugs on both BP and PP . Clinic measurements seem to be the least reliable method , particularly in the detection of differences in PP The antihypertensive efficacy of the angiotensin II receptor blocker olmesartan medoxomil has been shown to compare favourably with that of other antihypertensive agents . This r and omized , double-blind study compared the antihypertensive efficacy of the starting dose of olmesartan medoxomil with that of the calcium channel blocker amlodipine besylate ( amlodipine ) in subjects with mild-to-moderate hypertension . Following a 4-week , single-blind , placebo run-in period , 440 subjects aged ⩾18 years were r and omized to the starting dose of olmesartan medoxomil ( 20 mg/day ) , amlodipine ( 5 mg/day ) , or placebo for 8 weeks . Subjects were evaluated by  24-h ambulatory blood pressure monitoring ( ABPM ) and by seated cuff blood pressure ( BP ) measurements at trough . The primary end point was the change from baseline in mean 24-h diastolic blood pressure ( DBP ) by ABPM at Week 8 . Secondary end points included change from baseline in mean 24-h ambulatory systolic blood pressure ( SBP ) at 8 weeks , change from baseline in mean seated trough cuff DBP and SBP measurements , and response and control rates for DBP < 90 and < 85 mmHg . Control rates for SBP < 140 and < 130 mmHg were also calculated . Olmesartan medoxomil and amlodipine produced significantly greater reductions in ambulatory and seated DBP and SBP compared with placebo . Mean reductions in ambulatory and seated BP were similar between the two active agents ; however , in the olmesartan medoxomil group , significantly more patients achieved the SBP goal of < 130 mmHg and the DBP goal of < 85 mmHg . Both drugs were well tolerated at the recommended starting dose . Although amlodipine was associated with a higher incidence of oedema , this did not reach statistical significance . Olmesartan medoxomil is an effective antihypertensive agent , with BP-lowering efficacy at the starting dose similar to that of amlodipine , and is associated with more patients achieving the rigorous BP goals of SBP < 130 mmHg and DBP < 85 mmHg Abstract . Objective : The aim of this study was to measure the time – effect profiles of a once-daily administered valsartan/hydrochlorothiazide combination and amlodipine on blood pressure using various indices derived from 24-h ambulatory blood pressure ( BP ) monitoring . Methods : Of the 310 r and omized out patients with uncomplicated mild-to-moderate primary hypertension , 259 ( 133 on valsartan/hydrochlorothiazide , 126 on amlodipine ) were eligible for analysis . After a 2-week placebo wash-out period , the patients were r and omly allocated to treatment with either valsartan 80 mg once daily ( o.d . ) or amlodipine 5 mg o.d . for 4 weeks ; in the case of an unsatisfactory blood pressure response , the treatments could be respectively changed to the fixed combination of valsartan 80 mg plus hydrochlorothiazide 12.5 mg o.d . or amlodipine 10 mg o.d . for a further 8 weeks . The trough : peak ratio ( global and individualized approaches ) and smoothness index ( i.e. , the ratio between the average of the 24-hourly BP changes after treatment and the corresponding st and ard deviation ) were calculated from 24-h ambulatory blood pressure recordings made after the placebo period and after 4 weeks and 12 weeks of active treatment . Results : Both regimens effectively lowered systolic and diastolic ambulatory pressures after 4 weeks and 12 weeks ( all P<0.001 ) but , among the responders , the valsartan/hydrochlorothiazide combination had a greater antihypertensive effect during the night-time hours after 12 weeks ( P=0.03/0.02 ) . In the responders , the placebo-adjusted , mean trough : peak ratios were 0.76/0.74 in the valsartan/hydrochlorothiazide group ( n=111 ) and 0.66/0.62 in the amlodipine group (n=101).The corresponding global trough : peak ratios were 0.61/0.57 for the valsartan/hydrochlorothiazide combination and 0.56/0.56 for amlodipine . However , the between-group differences in individual or global trough : peak ratios were not significant . The smoothness index was slightly , but insignificantly , greater for valsartan/hydrochlorothiazide than for amlodipine in the responders and the groups as a whole . Conclusion : Valsartan/hydrochlorothiazide and amlodipine were equally effective in reducing ambulatory BP , but the valsartan/hydrochlorothiazide combination led to more homogeneous BP control during the inter-dosing interval . Trough : peak ratio and smoothness index did not reflect this finding accurately This multicenter study evaluated the efficacy of c and esartan cilexetil , an angiotensin II type 1 receptor antagonist , used alone or in combination with amlodipine or in combination with amlodipine and hydrochlorothiazide in the treatment of patients with moderate-to-severe essential hypertension . After a 2-week , single-blind , placebo run-in period , patients entered a 12-week , open-label , dose-titration period . The c and esartan cilexetil dose was increased from 8 to 16 mg once daily ; amlodipine ( 5 mg once daily ) , hydrochlorothiazide ( 25 mg once daily ) , and additional medication were also added sequentially if necessary . Patients then entered a final 4-week , parallel-group , double-blind , r and omized , placebo-controlled withdrawal period of c and esartan alone .  A total of 216 patients were recruited . After a 2-week run-in period on placebo tablets , mean sitting blood pressure ( BP ) was 175/108 mm Hg . At the end of the 12-week dose-titration/maintenance period , mean sitting BP fell to 141/88 mm Hg . In 67 patients who were r and omized to placebo and had their c and esartan withdrawn , there was a highly significant increase in mean systolic/diastolic BP ( 13/6 mm Hg ) compared with those patients who continued with c and esartan ( ANCOVA , P < 0.0001 ) . In conclusion , c and esartan cilexetil is an effective BP-lowering drug when used alone or in combination with amlodipine or amlodipine plus hydrochlorothiazide in the treatment of moderate-to-severe essential hypertension . The drug was well tolerated throughout the investigation period The antihypertensive efficacy and tolerability profiles of the selective AT1 receptor antagonists telmisartan and losartan were compared with placebo in a 6-week , multinational , multicentre , r and omised , double-blind , double-dummy , parallel-group study of 223 patients with mild-to-moderate hypertension , defined as clinic diastolic blood pressure ( DBP ) ⩾95 and ⩽114 mm Hg , clinic systolic blood pressure ( SBP ) ⩾140 and ⩽200 mm Hg , and 24-h ambulatory DBP ⩾85 mm Hg . After a 4-week single-blind placebo run-in , eligible patients were r and omised to receive telmisartan 40 mg , telmisartan 80 mg , losartan 50 mg , or placebo . Ambulatory blood pressure monitoring ( ABPM ) after 6 weeks of double-blind therapy showed that all active treatments produced significant ( P < 0.01 ) reductions from baseline in 24-h mean sbp and dbp compared with placebo . during the 18-to-24 h period after dosing , the reductions in sbp/dbp  with telmisartan 40 mg ( 10.7/6.8 mm hg ) and 80 mg ( 12.2/7.1 mm hg ) were each significantly ( P < 0.05 ) greater than those observed for losartan 50 mg ( 6.0/3.7 mm hg ) , and losartan was no better than placebo . also for the 24-h mean blood pressure  , telmisartan 40 mg and 80 mg were significantly ( P < 0.05 ) better than losartan 50 mg . compared with losartan , telmisartan 80 mg produced significantly ( P < 0.05 ) greater reductions in both sbp and dbp during all monitored periods of the 24-h period , while telmisartan 40 mg produced significantly greater reductions in sbp and dbp in the night-time period ( 10.01 pm to 5.59 am ) ( P < 0.05 ) and in dbp in the morning period ( 6.00 am to 11.59 am ) ( P < 0.05 ) . all treatments were comparably well tolerated . telmisartan 40 mg and 80 mg once daily were effective and well tolerated in the treatment of mild-to-moderate hypertension , producing sustained 24-h blood pressure control which compared favourably with losartan The efficacy and tolerability of the combination of valsartan and hydrochlorothi-azide ( HCTZ ) were compared with that of amlodipine in reducing ambulatory blood pressure and plasma norepinephrine levels in patients with mild to moderate hypertension and at least 1 cardiovascular risk factor . At the end of a 2-week washout period , 92 out patients with a sitting diastolic blood pressure ≥95 and < 110 mm Hg , associated with at least 1 additional risk factor , were r and omly assigned to receive either valsartan 160 mg and HCTZ 12.5 mg once daily ( n=46 ) or amlodipine 10 mg alone once daily ( n=46 ) for 12 weeks , according to a prospect i ve , r and omized , open-label , blinded end point , parallel-group design . At the end of the washout period and after 6 and 12 weeks of active treatment , 24-hour ambulatory blood pressure monitoring was performed , and clinical blood pressure and heart rate and plasma norepinephrine levels were assessed ( by high-performance liquid chromatography ) . Both the valsartan/HCTZ combination and amlodipine had a demonstrable antihypertensive effect , but the combination showed an antihypertensive effect significantly greater than that of amlodipine , as demonstrated by the 24-hour ( P < .001 ) , daytime ( P < .001 ) , and nighttime ambulatory blood pressure values ( P < .01 ) and by the clinical blood pressure values at trough , which were all significantly lower . Although the trough-to-peak ratios were similar in both groups , the smoothness indexes pertaining to both systolic and diastolic pressures were significantly higher ( P < .05 and P < .001 , respectively ) in patients receiving valsartan/HCTZ , suggesting the combination produces a more homogeneous antihypertensive effect . A significant increase in plasma norepinephrine levels was associated with amlodipine ( + 9 % at 6 weeks , + 15 % at 12 weeks ) but not with the valsartan/HCTZ combination . The valsartan/HCTZ combination was better tolerated than amlodipine , which was associated with a higher frequency of ankle edema . These results indicate that the combination of valsartan 16 
    Output:
    
agent
RESULTS The global antihypertensive activity of ARB differs from that observed with amlodipine in the sense that the magnitude of the reduction in the BP values does not essentially depend on the initial BP values nor on the dose used .
When only ARB were considered , the drug used was a determinant for systolic BP reduction , whereas for diastolic BP the influence was on the BP reduction and the duration of the antihypertensive activity .
The dose used had a particular influence on the duration of the antihypertensive activity for both systolic and diastolic BP .
CONCLUSION Among the ARB , the influence is on duration more than on the magnitude of BP reduction .
Dose , therefore , is an important factor in the duration of antihypertensive activity
***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: This study investigated the differences in the effect of an angiotensin converting enzyme inhibitor ( ACEI ) compared with an angiotensin receptor blocker ( ARB ) on blood pressure ( BP ) and pulse pressure ( PP ) measured in the clinic ( CBP and CPP , respectively ) , at home ( HBP , HPP ) and with ambulatory monitoring ( ABP , APP ) . Twenty-seven hypertensive patients were r and omised to receive lisinopril ( 20 mg ) or losartan ( 50 mg ) for 5 weeks , and were subsequently crossed-over to the alternative treatment for a second 5-week period . Measurements of CBP , 24-h ABP and 5-days HBP were performed before r and omisation and at the end of each treatment period . All measurement methods showed that lisinopril was more effective than losartan in reducing BP . However , the difference between the two drugs was demonstrated with greater precision using HBP ( P<0.001 ) than 24-h ABP ( P<0.01 ) , whereas the poorest precision for demonstrating this difference was provided by CBP ( P<0.05 ) . Lisinopril was also found more effective than losartan in reducing HPP ( P=0.01 ) and 24-h APP ( P=0.03 ) whereas no such a difference was detected using measurements of CPP . It was concluded that the antihypertensive drugs may differ in their effects not only on BP , but also on PP . HBP monitoring appears to be as reliable as 24-h ABP monitoring in detecting differences in the effect of drugs on both BP and PP . Clinic measurements seem to be the least reliable method , particularly in the detection of differences in PP The antihypertensive efficacy of the angiotensin II receptor blocker olmesartan medoxomil has been shown to compare favourably with that of other antihypertensive agents . This r and omized , double-blind study compared the antihypertensive efficacy of the starting dose of olmesartan medoxomil with that of the calcium channel blocker amlodipine besylate ( amlodipine ) in subjects with mild-to-moderate hypertension . Following a 4-week , single-blind , placebo run-in period , 440 subjects aged ⩾18 years were r and omized to the starting dose of olmesartan medoxomil ( 20 mg/day ) , amlodipine ( 5 mg/day ) , or placebo for 8 weeks . Subjects were evaluated by  24-h ambulatory blood pressure monitoring ( ABPM ) and by seated cuff blood pressure ( BP ) measurements at trough . The primary end point was the change from baseline in mean 24-h diastolic blood pressure ( DBP ) by ABPM at Week 8 . Secondary end points included change from baseline in mean 24-h ambulatory systolic blood pressure ( SBP ) at 8 weeks , change from baseline in mean seated trough cuff DBP and SBP measurements , and response and control rates for DBP < 90 and < 85 mmHg . Control rates for SBP < 140 and < 130 mmHg were also calculated . Olmesartan medoxomil and amlodipine produced significantly greater reductions in ambulatory and seated DBP and SBP compared with placebo . Mean reductions in ambulatory and seated BP were similar between the two active agents ; however , in the olmesartan medoxomil group , significantly more patients achieved the SBP goal of < 130 mmHg and the DBP goal of < 85 mmHg . Both drugs were well tolerated at the recommended starting dose . Although amlodipine was associated with a higher incidence of oedema , this did not reach statistical significance . Olmesartan medoxomil is an effective antihypertensive agent , with BP-lowering efficacy at the starting dose similar to that of amlodipine , and is associated with more patients achieving the rigorous BP goals of SBP < 130 mmHg and DBP < 85 mmHg Abstract . Objective : The aim of this study was to measure the time – effect profiles of a once-daily administered valsartan/hydrochlorothiazide combination and amlodipine on blood pressure using various indices derived from 24-h ambulatory blood pressure ( BP ) monitoring . Methods : Of the 310 r and omized out patients with uncomplicated mild-to-moderate primary hypertension , 259 ( 133 on valsartan/hydrochlorothiazide , 126 on amlodipine ) were eligible for analysis . After a 2-week placebo wash-out period , the patients were r and omly allocated to treatment with either valsartan 80 mg once daily ( o.d . ) or amlodipine 5 mg o.d . for 4 weeks ; in the case of an unsatisfactory blood pressure response , the treatments could be respectively changed to the fixed combination of valsartan 80 mg plus hydrochlorothiazide 12.5 mg o.d . or amlodipine 10 mg o.d . for a further 8 weeks . The trough : peak ratio ( global and individualized approaches ) and smoothness index ( i.e. , the ratio between the average of the 24-hourly BP changes after treatment and the corresponding st and ard deviation ) were calculated from 24-h ambulatory blood pressure recordings made after the placebo period and after 4 weeks and 12 weeks of active treatment . Results : Both regimens effectively lowered systolic and diastolic ambulatory pressures after 4 weeks and 12 weeks ( all P<0.001 ) but , among the responders , the valsartan/hydrochlorothiazide combination had a greater antihypertensive effect during the night-time hours after 12 weeks ( P=0.03/0.02 ) . In the responders , the placebo-adjusted , mean trough : peak ratios were 0.76/0.74 in the valsartan/hydrochlorothiazide group ( n=111 ) and 0.66/0.62 in the amlodipine group (n=101).The corresponding global trough : peak ratios were 0.61/0.57 for the valsartan/hydrochlorothiazide combination and 0.56/0.56 for amlodipine . However , the between-group differences in individual or global trough : peak ratios were not significant . The smoothness index was slightly , but insignificantly , greater for valsartan/hydrochlorothiazide than for amlodipine in the responders and the groups as a whole . Conclusion : Valsartan/hydrochlorothiazide and amlodipine were equally effective in reducing ambulatory BP , but the valsartan/hydrochlorothiazide combination led to more homogeneous BP control during the inter-dosing interval . Trough : peak ratio and smoothness index did not reflect this finding accurately This multicenter study evaluated the efficacy of c and esartan cilexetil , an angiotensin II type 1 receptor antagonist , used alone or in combination with amlodipine or in combination with amlodipine and hydrochlorothiazide in the treatment of patients with moderate-to-severe essential hypertension . After a 2-week , single-blind , placebo run-in period , patients entered a 12-week , open-label , dose-titration period . The c and esartan cilexetil dose was increased from 8 to 16 mg once daily ; amlodipine ( 5 mg once daily ) , hydrochlorothiazide ( 25 mg once daily ) , and additional medication were also added sequentially if necessary . Patients then entered a final 4-week , parallel-group , double-blind , r and omized , placebo-controlled withdrawal period of c and esartan alone .  A total of 216 patients were recruited . After a 2-week run-in period on placebo tablets , mean sitting blood pressure ( BP ) was 175/108 mm Hg . At the end of the 12-week dose-titration/maintenance period , mean sitting BP fell to 141/88 mm Hg . In 67 patients who were r and omized to placebo and had their c and esartan withdrawn , there was a highly significant increase in mean systolic/diastolic BP ( 13/6 mm Hg ) compared with those patients who continued with c and esartan ( ANCOVA , P < 0.0001 ) . In conclusion , c and esartan cilexetil is an effective BP-lowering drug when used alone or in combination with amlodipine or amlodipine plus hydrochlorothiazide in the treatment of moderate-to-severe essential hypertension . The drug was well tolerated throughout the investigation period The antihypertensive efficacy and tolerability profiles of the selective AT1 receptor antagonists telmisartan and losartan were compared with placebo in a 6-week , multinational , multicentre , r and omised , double-blind , double-dummy , parallel-group study of 223 patients with mild-to-moderate hypertension , defined as clinic diastolic blood pressure ( DBP ) ⩾95 and ⩽114 mm Hg , clinic systolic blood pressure ( SBP ) ⩾140 and ⩽200 mm Hg , and 24-h ambulatory DBP ⩾85 mm Hg . After a 4-week single-blind placebo run-in , eligible patients were r and omised to receive telmisartan 40 mg , telmisartan 80 mg , losartan 50 mg , or placebo . Ambulatory blood pressure monitoring ( ABPM ) after 6 weeks of double-blind therapy showed that all active treatments produced significant ( P < 0.01 ) reductions from baseline in 24-h mean sbp and dbp compared with placebo . during the 18-to-24 h period after dosing , the reductions in sbp/dbp  with telmisartan 40 mg ( 10.7/6.8 mm hg ) and 80 mg ( 12.2/7.1 mm hg ) were each significantly ( P < 0.05 ) greater than those observed for losartan 50 mg ( 6.0/3.7 mm hg ) , and losartan was no better than placebo . also for the 24-h mean blood pressure  , telmisartan 40 mg and 80 mg were significantly ( P < 0.05 ) better than losartan 50 mg . compared with losartan , telmisartan 80 mg produced significantly ( P < 0.05 ) greater reductions in both sbp and dbp during all monitored periods of the 24-h period , while telmisartan 40 mg produced significantly greater reductions in sbp and dbp in the night-time period ( 10.01 pm to 5.59 am ) ( P < 0.05 ) and in dbp in the morning period ( 6.00 am to 11.59 am ) ( P < 0.05 ) . all treatments were comparably well tolerated . telmisartan 40 mg and 80 mg once daily were effective and well tolerated in the treatment of mild-to-moderate hypertension , producing sustained 24-h blood pressure control which compared favourably with losartan The efficacy and tolerability of the combination of valsartan and hydrochlorothi-azide ( HCTZ ) were compared with that of amlodipine in reducing ambulatory blood pressure and plasma norepinephrine levels in patients with mild to moderate hypertension and at least 1 cardiovascular risk factor . At the end of a 2-week washout period , 92 out patients with a sitting diastolic blood pressure ≥95 and < 110 mm Hg , associated with at least 1 additional risk factor , were r and omly assigned to receive either valsartan 160 mg and HCTZ 12.5 mg once daily ( n=46 ) or amlodipine 10 mg alone once daily ( n=46 ) for 12 weeks , according to a prospect i ve , r and omized , open-label , blinded end point , parallel-group design . At the end of the washout period and after 6 and 12 weeks of active treatment , 24-hour ambulatory blood pressure monitoring was performed , and clinical blood pressure and heart rate and plasma norepinephrine levels were assessed ( by high-performance liquid chromatography ) . Both the valsartan/HCTZ combination and amlodipine had a demonstrable antihypertensive effect , but the combination showed an antihypertensive effect significantly greater than that of amlodipine , as demonstrated by the 24-hour ( P < .001 ) , daytime ( P < .001 ) , and nighttime ambulatory blood pressure values ( P < .01 ) and by the clinical blood pressure values at trough , which were all significantly lower . Although the trough-to-peak ratios were similar in both groups , the smoothness indexes pertaining to both systolic and diastolic pressures were significantly higher ( P < .05 and P < .001 , respectively ) in patients receiving valsartan/HCTZ , suggesting the combination produces a more homogeneous antihypertensive effect . A significant increase in plasma norepinephrine levels was associated with amlodipine ( + 9 % at 6 weeks , + 15 % at 12 weeks ) but not with the valsartan/HCTZ combination . The valsartan/HCTZ combination was better tolerated than amlodipine , which was associated with a higher frequency of ankle edema . These results indicate that the combination of valsartan 16 
    Output:
    