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: The antihypertensive effects of telmisartan 80 mg versus valsartan 160 mg , both combined with hydrochlorothiazide ( HCTZ ) 25 mg , were assessed in a pooled analysis from two large trials with identical study design s in patients with stage 1–2 hypertension . The trials were double-blind with a 4:4:1 r and omization scheme to compare once-daily telmisartan 80 mg and HCTZ 25 mg versus once-daily valsartan 160 mg and HCTZ 25 mg versus once-daily placebo on reductions in clinic blood pressure ( BP ) . The primary end point was changes from baseline in BP at the end of 8 weeks . In total , 2121 patients were r and omized ( telmisartan – HCTZ , 942 , valsartan – HCTZ , 952 , and placebo , 227 ) and had baseline seated BPs of 154/102 and 155/102 mm Hg in the two studies , respectively .  Changes from baseline in BP after administration of telmisartan – HCTZ ( −24.5/−18.0 mm Hg ) were significantly greater than for both placebo ( −4.1/−6.5 mm Hg ) and valsartan – HCTZ ( −22.3/−16.8 mm Hg ) ( versus placebo , P<0.0001 for systolic and diastolic BP ; versus valsartan – HCTZ , P=0.0004 for systolic BP and P=0.0019 for diastolic BP ) . Adverse event rates were higher in the placebo group than in the active treatment groups ( placebo , 41 % , telmisartan – HCTZ , 30 % , and valsartan – HCTZ , 30 % , P<0.05 ) . These data confirm that telmisartan – HCTZ at doses of 80/25 mg lowered systolic and diastolic BP to a greater extent than valsartan – HCTZ at doses of 160/25 mg in stage 1–2 hypertension . The magnitude of the BP-lowering effect provides support for the use of angiotensin receptor blockers with higher doses of a thiazide diuretic ( 25 mg ) to improve hypertension control Increased arterial stiffness , as estimated from aortic pulse wave velocity ( Ao-PWV ) , and albuminuria are independent predictors for cardiovascular disease in type 2 diabetes mellitus ( T2DM ) . Whether angiotensin receptor blockers ( ARBs ) , drugs with cardio-renal protective effects , improve Ao-PWV to a greater extent than other equipotent antihypertensive medications remains unclear . After a 4-week washout phase , we compared the effects of valsartan ( n=66 ) , an ARB , with that of amlodipine ( n=65 ) , a calcium channel blocker on Ao-PWV in 131 T2DM patients with pulse pressure ( PP ) ≥60 mm Hg and raised albumin excretion rate ( AER ) in a 24-week r and omized , double-blind , parallel group study . Hydrochlorothiazide ( HCTZ ) 25 mg/d was added to valsartan 160 mg and amlodipine 5 mg/od uptitrated to 10 mg/od after 4 weeks to ensure equivalent BP control . After 24 weeks brachial and central aortic PP had fallen to a similar extent with attained mean ( SD ) brachial and central PP of 61.6 ( 13.6 ) and 47.3 ( 14.1 ) mm Hg in the valsartan/HCTZ group and 61.5 ( 12.2 ) and 47.3 ( 9.9 ) mm Hg in the amlodipine group , respectively . Ao-PWV showed a significantly greater reduction , mean ( 95 % CI ) , −0.9 m/s ( −1.4 to −0.3 ) for valsartan/HCTZ compared to amlodipine ( P=0.002 ) . AER fell significantly only with Val/HCTZ from 30.8(20.4 , 46.5 ) to 18.2(12.5 , 26.3 ) mcg/min , ( P=0.01 ) with between treatment difference in favor of Val/HCTZ of −15.3mcg/min ( P<0.001 ) . Changes in AER and Ao-PWV were not correlated . Valsartan/HCTZ improves arterial stiffness and AER to a significantly greater extent than amlodipine despite similar central and brachial BP control . These 2 effects , which appear independent of each other , may explain the specific cardio-renal protective properties of ARBs BACKGROUND The aim of the study was to evaluate whether the combined treatment of calcium channel blocker , amlodipine and beta-blocker , betaxolol , favorably affects cardiac autonomic nervous activity ( CANA ) and health-related quality of life ( HRQL ) . METHODS AND RESULTS A total of 65 patients with a poor blood pressure ( BP ) control with a low dose amlodipine therapy were r and omly assigned to the amlodipine dose-up group ( n=21 ) and betaxolol adding group ( n=44 ) . Before and after a 6-month treatment , BP , heart rate variability ( HRV ) , HRQL and blood chemistries were evaluated . Low frequency ( LF ) spectra/high frequency ( HF ) spectra and HF/total power spectra ( TP ) were calculated as indexes of CANA , and HRQL was assessed by the question naire sheets . BP was well controlled in all patients of the present study . In the betaxolol adding group , LF/HF decreased ( 2.1+/-1.9 to 1.3+/-0.9 , p<0.05 ) and HF/TP reciprocally increased ( 0.41+/-0.17 to 0.52+/-0.18 , p<0.05 ) , whereas the amlodipine dose-up group showed no significant changes in the HRV . HRQL was significantly improved in the betaxolol adding group , whereas it remained unchanged in the amlodipine dose-up group . Blood chemistries remained unchanged except for the slightly increased plasma brain natriuretic peptide concentrations in the betaxolol adding group ( 36+/-47 to 62+/-62 pg/ml , p<0.05 ) . CONCLUSIONS Combined treatment of amlodipine and betaxolol appears to be more useful than amlodipine dose-up therapy , because combined treatment improves CANA and HRQL OBJECTIVE To evaluate the 24 h antihypertensive efficacy and duration of action of felodipine extended release ( ER ) in comparison with two other long acting dihydropyridine calcium antagonists , amlodipine and nifedipine gastrointestinal therapeutic system ( GITS ) , in patients with mild to moderate essential hypertension substantiated by ambulatory blood pressure ( BP ) monitoring . DESIGN R and omized , forced titration , parallel group study . Clinic BP was measured at every patient 's visit , and 24 h ambulatory BP was monitored at baseline and at the end of each dose-titration period . SETTING Single centre : hypertension research unit in Quebec City , Quebec . PATIENTS There were 89 patients enrolled into the study . Eighty-four eligible patients were r and omized , and 83 completed the study and were included in the final efficacy analysis . INTERVENTIONS Following a two-to four-week washout period ( baseline ) , patients were r and omly allocated to receive felodipine ER 5 mg , amlodipine 5 mg or nifedipine GITS 30 mg for four weeks ( low dose ) . All study patients had their daily dose doubled to felodipine ER 10 mg , amlodipine 10 mg or nifedipine GITS 60 mg for a further four weeks ( high dose ) . MAIN RESULTS Significant ( P < 0.001 ) and similar changes from baseline in clinic BP were observed in all treatment groups for low and high doses . Ambulatory BP profiles showed comparable blood pressure reductions with felodipine ER and amlodipine , and a trend towards a lesser reduction with nifedipine GITS during 24 h , daytime and night-time periods . BP loads were similarly reduced with the three treatments . Trough to peak ratios ( T : Ps ) were calculated from 24 h ambulatory BP curves according to two different approaches : for diastolic and systolic BP , respectively , the global approach produced T : Ps of 0.49 and 0.50 with felodipine ER 5 mg ; 0.50 and 0.34 with felodipine ER 10 mg ; 0.70 and 0.60 with amlodipine 5 mg ; 0.88 and 0.82 with amlodipine 10 mg ; 0.65 and 0.55 with nifedipine GITS 30 mg ; 0.68 and 0.53 with nifedipine GITS 60 mg . T : Ps in the individual approach were 0.07 and 0.10 with felodipine ER 5 mg ; 0.23 and 0.31 with felodipine ER 10 mg ; 0.22 and 0.31 with amlodipine 5 mg ; 0.45 and 0.58 with amlodipine 10 mg ; 0.27 and 0.31 with nifedipine GITS 30 mg ; and 0.24 and 0.40 with nifedipine GITS 60 mg . CONCLUSION There was no evidence in this study of a difference among felodipine ER , amlodipine and nifedipine GITS in lowering ambulatory or clinic BP . Treatment based on ambulatory BP may be preferable to treatment guided by T : Ps because ambulatory BP is firmly established as a predictor of cardiovascular risk . Furthermore , there is no consensus on how to calculate T : Ps , and different methods of calculation may give divergent results OBJECTIVE --To assess the effectiveness of angiotensin converting enzyme inhibition in preventing the development of diabetic nephropathy ( albuminuria greater than 300 mg/24h ) . DESIGN --Open r and omised controlled study of four years ' duration . SETTING --Outpatient diabetic clinic in tertiary referral centre . PATIENTS --44 normotensive ( mean blood pressure 127/78 ( SD 12/10 ) mm Hg ) insulin dependent diabetic patients with persistent microalbuminuria ( 30 - 300 mg/24h ) . INTERVENTIONS --The treatment group ( n = 21 ) was initially given captopril ( 25 mg/24 h ) . The dose was increased to 100 mg/24 h during the first 16 months and thiazide was added after 30 months . The remaining 23 patients were left untreated . MAIN OUTCOME MEASURES --Albuminuria , kidney function , development of diabetic nephropathy ( albuminuria greater than 300 mg/24 h ) , and arterial blood pressure . RESULTS -- Clinical and laboratory variables were comparable at baseline . Urinary excretion of albumin was gradually reduced from 82 ( 66 - 106 ) to 57 ( 39 - 85 ) mg/24 h ( geometric mean ( 95 % confidence interval ) ) in the captopril treated group , whereas an increase from 105(77 - 153 ) to 166 ( 83 - 323 ) mg/24 h occurred in the control group ( p less than 0.05 ) . Seven of the untreated patients progressed to diabetic nephropathy , whereas none of the captopril treated patients developed clinical overt diabetic nephropathy ( p less than 0.05 ) . Systemic blood pressure , glomerular filtration rate , haemoglobin A1c concentration , and urinary excretion of sodium and urea remained practically unchanged in the two groups . CONCLUSIONS --The findings suggest that angiotensin converting enzyme inhibition postpones the development of clinical overt diabetic nephropathy in normotensive insulin dependent diabetic patients with persistent microalbuminuria The efficacy of once-a-day cilazapril ( a new long acting converting enzyme inhibitor ) therapy for the 24 h control of hypertension and its effects on the renin-angiotensin axis were investigated . Twenty-four uncomplicated hypertensive patients whose sitting diastolic blood pressures remained within 94 to 114 mmHg after four weeks of placebo were r and omly assigned on a double-blind basis to receive either continued placebo or cilazapril therapy at a single dose of 1.25 , 2.5 or 5.0 mg/day for a further four weeks . At the end of weeks 4 and 8 , systolic and diastolic blood pressures and heart rates were recorded , supine and st and ing , at 0 , 2 , 4 , 6 , 9 , 12 and 24 h following 
    Output:
    
agent
Effects of antihypertensive drugs on SBP variability are dose-dependent and persist when used in combinations .
Use of a high dose of a calcium channel blocker alone or in combination with other agents is therefore likely to be particularly effective in prevention of stroke
***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: The antihypertensive effects of telmisartan 80 mg versus valsartan 160 mg , both combined with hydrochlorothiazide ( HCTZ ) 25 mg , were assessed in a pooled analysis from two large trials with identical study design s in patients with stage 1–2 hypertension . The trials were double-blind with a 4:4:1 r and omization scheme to compare once-daily telmisartan 80 mg and HCTZ 25 mg versus once-daily valsartan 160 mg and HCTZ 25 mg versus once-daily placebo on reductions in clinic blood pressure ( BP ) . The primary end point was changes from baseline in BP at the end of 8 weeks . In total , 2121 patients were r and omized ( telmisartan – HCTZ , 942 , valsartan – HCTZ , 952 , and placebo , 227 ) and had baseline seated BPs of 154/102 and 155/102 mm Hg in the two studies , respectively .  Changes from baseline in BP after administration of telmisartan – HCTZ ( −24.5/−18.0 mm Hg ) were significantly greater than for both placebo ( −4.1/−6.5 mm Hg ) and valsartan – HCTZ ( −22.3/−16.8 mm Hg ) ( versus placebo , P<0.0001 for systolic and diastolic BP ; versus valsartan – HCTZ , P=0.0004 for systolic BP and P=0.0019 for diastolic BP ) . Adverse event rates were higher in the placebo group than in the active treatment groups ( placebo , 41 % , telmisartan – HCTZ , 30 % , and valsartan – HCTZ , 30 % , P<0.05 ) . These data confirm that telmisartan – HCTZ at doses of 80/25 mg lowered systolic and diastolic BP to a greater extent than valsartan – HCTZ at doses of 160/25 mg in stage 1–2 hypertension . The magnitude of the BP-lowering effect provides support for the use of angiotensin receptor blockers with higher doses of a thiazide diuretic ( 25 mg ) to improve hypertension control Increased arterial stiffness , as estimated from aortic pulse wave velocity ( Ao-PWV ) , and albuminuria are independent predictors for cardiovascular disease in type 2 diabetes mellitus ( T2DM ) . Whether angiotensin receptor blockers ( ARBs ) , drugs with cardio-renal protective effects , improve Ao-PWV to a greater extent than other equipotent antihypertensive medications remains unclear . After a 4-week washout phase , we compared the effects of valsartan ( n=66 ) , an ARB , with that of amlodipine ( n=65 ) , a calcium channel blocker on Ao-PWV in 131 T2DM patients with pulse pressure ( PP ) ≥60 mm Hg and raised albumin excretion rate ( AER ) in a 24-week r and omized , double-blind , parallel group study . Hydrochlorothiazide ( HCTZ ) 25 mg/d was added to valsartan 160 mg and amlodipine 5 mg/od uptitrated to 10 mg/od after 4 weeks to ensure equivalent BP control . After 24 weeks brachial and central aortic PP had fallen to a similar extent with attained mean ( SD ) brachial and central PP of 61.6 ( 13.6 ) and 47.3 ( 14.1 ) mm Hg in the valsartan/HCTZ group and 61.5 ( 12.2 ) and 47.3 ( 9.9 ) mm Hg in the amlodipine group , respectively . Ao-PWV showed a significantly greater reduction , mean ( 95 % CI ) , −0.9 m/s ( −1.4 to −0.3 ) for valsartan/HCTZ compared to amlodipine ( P=0.002 ) . AER fell significantly only with Val/HCTZ from 30.8(20.4 , 46.5 ) to 18.2(12.5 , 26.3 ) mcg/min , ( P=0.01 ) with between treatment difference in favor of Val/HCTZ of −15.3mcg/min ( P<0.001 ) . Changes in AER and Ao-PWV were not correlated . Valsartan/HCTZ improves arterial stiffness and AER to a significantly greater extent than amlodipine despite similar central and brachial BP control . These 2 effects , which appear independent of each other , may explain the specific cardio-renal protective properties of ARBs BACKGROUND The aim of the study was to evaluate whether the combined treatment of calcium channel blocker , amlodipine and beta-blocker , betaxolol , favorably affects cardiac autonomic nervous activity ( CANA ) and health-related quality of life ( HRQL ) . METHODS AND RESULTS A total of 65 patients with a poor blood pressure ( BP ) control with a low dose amlodipine therapy were r and omly assigned to the amlodipine dose-up group ( n=21 ) and betaxolol adding group ( n=44 ) . Before and after a 6-month treatment , BP , heart rate variability ( HRV ) , HRQL and blood chemistries were evaluated . Low frequency ( LF ) spectra/high frequency ( HF ) spectra and HF/total power spectra ( TP ) were calculated as indexes of CANA , and HRQL was assessed by the question naire sheets . BP was well controlled in all patients of the present study . In the betaxolol adding group , LF/HF decreased ( 2.1+/-1.9 to 1.3+/-0.9 , p<0.05 ) and HF/TP reciprocally increased ( 0.41+/-0.17 to 0.52+/-0.18 , p<0.05 ) , whereas the amlodipine dose-up group showed no significant changes in the HRV . HRQL was significantly improved in the betaxolol adding group , whereas it remained unchanged in the amlodipine dose-up group . Blood chemistries remained unchanged except for the slightly increased plasma brain natriuretic peptide concentrations in the betaxolol adding group ( 36+/-47 to 62+/-62 pg/ml , p<0.05 ) . CONCLUSIONS Combined treatment of amlodipine and betaxolol appears to be more useful than amlodipine dose-up therapy , because combined treatment improves CANA and HRQL OBJECTIVE To evaluate the 24 h antihypertensive efficacy and duration of action of felodipine extended release ( ER ) in comparison with two other long acting dihydropyridine calcium antagonists , amlodipine and nifedipine gastrointestinal therapeutic system ( GITS ) , in patients with mild to moderate essential hypertension substantiated by ambulatory blood pressure ( BP ) monitoring . DESIGN R and omized , forced titration , parallel group study . Clinic BP was measured at every patient 's visit , and 24 h ambulatory BP was monitored at baseline and at the end of each dose-titration period . SETTING Single centre : hypertension research unit in Quebec City , Quebec . PATIENTS There were 89 patients enrolled into the study . Eighty-four eligible patients were r and omized , and 83 completed the study and were included in the final efficacy analysis . INTERVENTIONS Following a two-to four-week washout period ( baseline ) , patients were r and omly allocated to receive felodipine ER 5 mg , amlodipine 5 mg or nifedipine GITS 30 mg for four weeks ( low dose ) . All study patients had their daily dose doubled to felodipine ER 10 mg , amlodipine 10 mg or nifedipine GITS 60 mg for a further four weeks ( high dose ) . MAIN RESULTS Significant ( P < 0.001 ) and similar changes from baseline in clinic BP were observed in all treatment groups for low and high doses . Ambulatory BP profiles showed comparable blood pressure reductions with felodipine ER and amlodipine , and a trend towards a lesser reduction with nifedipine GITS during 24 h , daytime and night-time periods . BP loads were similarly reduced with the three treatments . Trough to peak ratios ( T : Ps ) were calculated from 24 h ambulatory BP curves according to two different approaches : for diastolic and systolic BP , respectively , the global approach produced T : Ps of 0.49 and 0.50 with felodipine ER 5 mg ; 0.50 and 0.34 with felodipine ER 10 mg ; 0.70 and 0.60 with amlodipine 5 mg ; 0.88 and 0.82 with amlodipine 10 mg ; 0.65 and 0.55 with nifedipine GITS 30 mg ; 0.68 and 0.53 with nifedipine GITS 60 mg . T : Ps in the individual approach were 0.07 and 0.10 with felodipine ER 5 mg ; 0.23 and 0.31 with felodipine ER 10 mg ; 0.22 and 0.31 with amlodipine 5 mg ; 0.45 and 0.58 with amlodipine 10 mg ; 0.27 and 0.31 with nifedipine GITS 30 mg ; and 0.24 and 0.40 with nifedipine GITS 60 mg . CONCLUSION There was no evidence in this study of a difference among felodipine ER , amlodipine and nifedipine GITS in lowering ambulatory or clinic BP . Treatment based on ambulatory BP may be preferable to treatment guided by T : Ps because ambulatory BP is firmly established as a predictor of cardiovascular risk . Furthermore , there is no consensus on how to calculate T : Ps , and different methods of calculation may give divergent results OBJECTIVE --To assess the effectiveness of angiotensin converting enzyme inhibition in preventing the development of diabetic nephropathy ( albuminuria greater than 300 mg/24h ) . DESIGN --Open r and omised controlled study of four years ' duration . SETTING --Outpatient diabetic clinic in tertiary referral centre . PATIENTS --44 normotensive ( mean blood pressure 127/78 ( SD 12/10 ) mm Hg ) insulin dependent diabetic patients with persistent microalbuminuria ( 30 - 300 mg/24h ) . INTERVENTIONS --The treatment group ( n = 21 ) was initially given captopril ( 25 mg/24 h ) . The dose was increased to 100 mg/24 h during the first 16 months and thiazide was added after 30 months . The remaining 23 patients were left untreated . MAIN OUTCOME MEASURES --Albuminuria , kidney function , development of diabetic nephropathy ( albuminuria greater than 300 mg/24 h ) , and arterial blood pressure . RESULTS -- Clinical and laboratory variables were comparable at baseline . Urinary excretion of albumin was gradually reduced from 82 ( 66 - 106 ) to 57 ( 39 - 85 ) mg/24 h ( geometric mean ( 95 % confidence interval ) ) in the captopril treated group , whereas an increase from 105(77 - 153 ) to 166 ( 83 - 323 ) mg/24 h occurred in the control group ( p less than 0.05 ) . Seven of the untreated patients progressed to diabetic nephropathy , whereas none of the captopril treated patients developed clinical overt diabetic nephropathy ( p less than 0.05 ) . Systemic blood pressure , glomerular filtration rate , haemoglobin A1c concentration , and urinary excretion of sodium and urea remained practically unchanged in the two groups . CONCLUSIONS --The findings suggest that angiotensin converting enzyme inhibition postpones the development of clinical overt diabetic nephropathy in normotensive insulin dependent diabetic patients with persistent microalbuminuria The efficacy of once-a-day cilazapril ( a new long acting converting enzyme inhibitor ) therapy for the 24 h control of hypertension and its effects on the renin-angiotensin axis were investigated . Twenty-four uncomplicated hypertensive patients whose sitting diastolic blood pressures remained within 94 to 114 mmHg after four weeks of placebo were r and omly assigned on a double-blind basis to receive either continued placebo or cilazapril therapy at a single dose of 1.25 , 2.5 or 5.0 mg/day for a further four weeks . At the end of weeks 4 and 8 , systolic and diastolic blood pressures and heart rates were recorded , supine and st and ing , at 0 , 2 , 4 , 6 , 9 , 12 and 24 h following 
    Output:
    