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: A multicentre , r and omised , placebo-controlled parallel group study comparing various doses of the combination diltiazem SR ( DTZ SR)/hydrochlorothiazide ( HCTZ ) with the monotherapies was performed to delineate the optimal antihypertensive dosage of the two drug combinations . The study was carried out in 298 patients with mild to moderate essential hypertension ( stable supine diastolic blood pressure , DBP , greater than or equal to 95 and less than or equal to 110 mmHg ) . After a single-blind placebo lead-in period lasting 4 - 6 weeks to establish stable baseline BP , the patients were r and omised to receive either placebo ( n = 75 ) , HCTZ ( n = 76 ) , DTZ SR ( n = 72 ) , or the combination of DTZ SR/HCTZ ( n = 75 ) . There were three 4-week evaluation periods with forced escalation of therapy as follows : HCTZ ( 6.25 , 6.25 , 12.5 mg twice daily ) , DTZ SR ( 60 , 90 , 120 mg twice daily ) , and the combination of DTZ SR/HCTZ ( 60/6.25 , 90/6.25 , 120/12.5 mg twice daily ) . DTZ SR/HCTZ ( 120/12.5 mg ) produced statistically significantly greater reductions in supine DBP compared with each monotherapy and placebo . The lower doses of DTZ SR/HCTZ ( 60/6.25 mg and 90/6.25 mg ) produced statistically significantly greater supine DBP reductions compared with DTZ SR monotherapy and placebo , but not compared with HCTZ monotherapy . A comparison of reduction in supine DBP between evaluation periods demonstrated a dose-response relationship for the combination therapy in reducing BP over the dosage range studied . Adverse clinical and laboratory events were not significantly different between the therapies . ( ABSTRACT TRUNCATED AT 250 WORDS BACKGROUND AND PURPOSE Converting enzyme inhibition and calcium blockade alter large arteries in hypertension . However , the heterogeneity of the response according to the site of cardiovascular measurements has never been investigated . METHODS In a double-blind study , we compared for 180 days 3 hypertensive patient groups treated with verapamil , tr and olapril , or their combination .  Using echo-Doppler technique and applanation tonometry , we independently measured mean pressure , local pulse pressure , arterial diameter , and distensibility at 3 arterial sites ( brachial and common carotid arteries and abdominal aorta ) , as well as cardiac and carotid wall structure . RESULTS Mean and pulse pressure decreased significantly to a greater extent with the drug combination . Regarding arterial and cardiac hemodynamics , significant and similar changes were noted in the 3 groups : decreases in abdominal aorta and carotid but not brachial diameter ; increases in carotid artery , abdominal aorta , and brachial distensibility even after adjustment to mean blood pressure reduction ; and more substantial regression of cardiac mass than carotid wall thickness . CONCLUSIONS This study shows that both compounds and more significantly combination therapy decreased mean and pulse pressures measured independently and that the changes in diameter , thickness , and stiffness were influenced primarily by the site of cardiovascular measurements , result ing in a predominant increase in distensibility of muscular arteries , little change in carotid wall thickness , but a significant regression of cardiac hypertrophy The efficacy and safety of enalapril and hydrochlorothiazide was investigated in a multicenter study of 81 patients with mild to moderate essential hypertension . The subjects were r and omly assigned to one of three groups and , following a placebo period , given enalapril maleate ( 20 mg ) , hydrochlorothiazide ( 12.5 mg ) , or a combination of the two drugs ( 32.5 mg ) . A significant decrease in blood pressure was observed after only 2 weeks in the enalapril and enalapril-hydrochlorothiazide groups . A double dose was required to achieve a satisfactory response in one-third of the patients in both the enalapril ( 9 of 27 ) and the enalapril-hydrochlorothiazide groups ( 8 of 27 ) . Adverse reactions included cough in one patient and mild hyperkalemia in another , both of whom received enalapril . Two patients on the drug combination developed side effects -- symptomatic orthostatic hypotension in one and impotence in the second . Enalapril alone and in combination with hydrochlorothiazide appears to be effective and well tolerated The efficacy , tolerability and metabolic effects of a fixed combination of lisinopril 10 mg and hydrochlorothiazide 12.5 mg ( L/HCTZ ) and those of the monocomponents were compared in 286 mild to moderate hypertensive patients in a 17-centre study using a double-blind , r and omized , parallel-group design . After 2 weeks of placebo run-in , patients were r and omized to one of the three treatments for 8 weeks . Supine and st and ing BPs were measured at peak blood levels ( 4 - 8 hours post dose ) after 4 weeks , and at trough blood levels ( 24 - 28 hours post dose ) after 8 weeks . The BP reduction from baseline was greater with L/HCTZ than with the monocomponents at weeks 4 and 8 ; at week 8 the reduction was statistically significant vs lisinopril for st and ing DBP ( P less than 0.027 ) but not for st and ing SBP ; the reduction was significant with L/HCTZ vs hydrochlorothiazide at week 4 [ P = 0.0002/0.0001 ( SBP/DBP ) supine ; P = 0.0002/0.0002 st and ing ] and at week 8 ( P = 0.0001/0.0001 supine and st and ing ) . Response at week 8 ( supine DBP less than or equal to 90 mm Hg ) with L/HCTZ ( 87.0 % ) was greater than with hydrochlorothiazide ( 29.0 % ; P less than 0.0001 ) and marginally greater than with lisinopril ( 74.2 % ; P = 0.069 ) . Heart rate fell statistically significantly more with L/HCTZ ( by 3.3 beats/minute ) than with HCTZ ( by 0.86 beats/minute ; P = 0.018 ) . L/HCTZ treatment significantly increased plasma uric acid levels compared with lisinopril . L/HCTZ decreased potassium , while lisinopril  increased potassium . L/HCTZ decreased cholesterol ; HCTZ increased it . Adverse effects were more common on L/HCTZ vs lisinopril ( P = 0.033 ) but not vs hydrochlorothiazide . ( ABSTRACT TRUNCATED AT 250 WORDS Summary The efficacy of cilazapril monotherapy and in combination with hydrochlorothiazide 12.5 mg was compared in a multicentre , double blind , r and omised parallel group study in 87 patients with mild to moderate essential hypertension over 8 weeks . After a 2 week single blind placebo run-in period , patients received either 2.5 mg cilazapril or 2.5 mg cilazapril plus 12.5 mg hydrochlorothiazide once daily . At Week 4 the cilazapril dose was increased from 2.5 mg to 5.0 mg if the mean sitting diastolic blood pressure was greater than 90 mmHg or had not decreased by more than 10 mmHg . After 8 weeks treatment 72 % of patients responded to 2.5 mg cilazapril increasing to 88 % with cilazapril 5.0 mg . For cilazapril plus hydrochlorothiazide , 83 % responded to 2.5 mg cilazapril increasing to 96 % on 5.0 mg cilazapril . The high response rate to low dose cilazapril monotherapy and hydrochlorothiazide combination therapy has important implication s for minimising the cost of therapy with ACE inhibitors Two hundred and eleven patients with mild or moderate hypertension , mean age 53.5 + /- 9.5 years ( range 24 - 70 ) were r and omised double-blind to treatment with either captopril 50 mg ( C50 ) , hydrochlorothiazide 25 mg ( HCTZ 25 ) , the fixed combination of captopril 50 mg and hydrochlorothiazide 25 mg ( C50/HCTZ 25 ) or placebo .  Blood pressure , heart rate , body weight and side effects were assessed at the end of the run-in period on placebo and after 4 , 6 , 8 weeks treatment at the same time , 20 - 24 h after the last dosing . Routine biochemical examinations were carried out on all patients after the placebo period as well as after 4 and 8 weeks . Blood pressure significantly decreased in all groups , but the mean percentage change from baseline was highly statistically significant at 8 weeks , for C50 and C50/HCTZ 25 groups . The incidence of clinical side effects was low and not statistically different for the four groups with few specific adverse effects ( one transient alteration of taste in captopril group ) . No patient was withdrawn from the study due to side effects . A better anti-hypertensive efficacy was obtained with the fixed combination captopril 50 mg/hydrochlorothiazide 25 mg once daily compared to placebo or each component alone , and without any difference in side effects Summary : In an 8-week , double-blind , r and omized , active-controlled , multicenter study with three parallel treatment groups , we compared the efficacy and safety of once-daily 20 mg quinapril plus 12.5 mg hydrochlorothi-azide ( HCTZ ) with each drug as monotherapy in patients with moderate to severe hypertension . Hypertensive out patients with supine diastolic blood pressure ( DBF ) ≤105 and ≥120 mm Hg at the end of a 2− to 4-week placebo-baseline period were r and omly assigned to one of the treatment groups . Of the 323 patients who were r and omized to double-blind medication , 297 completed the study , but 6 patients were excluded for violations of protocol ; therefore , statistical analysis was performed in 291 patients . Only 7 patients withdrew owing to lack of efficacy ( 2 receiving combination therapy ) . In all three treatment groups , clinical ly significant reductions in DBF were achieved . Combination therapy was statistically more effective than each component in both evaluable data and intent-to-treat analyses . The incidence of adverse events ( AE ) was 24 % in the quinapril monotherapy group , 14 % in the combination therapy group , and 11 % in the HCTZ monotherapy group . Orthostatic hypotension with related symptoms was observed in 4 patients ( 2 receiving quinapril monotherapy , 1 receiving HCTZ monotherapy , and 1 receiving combination therapy ) . Once-daily quinapril plus HCTZ provided increased reduction of DBF as compared with the monotherapies and was well tolerated in patients with moderate to severe hypertension BACKGROUND Most patients with hypertension require more than one agent to control blood pressure ( BP ) . The purpose of this study was to assess the efficacy and safety of the angiotensin II receptor blocker olmesartan medoxomil in combination with hydrochlorothiazide ( HCTZ ) . METHODS This was a r and omized , double-blind , factorial design study . After a placebo run-in period , eligible patients ( n = 502 ) with a baseline mean seated diastolic blood pressure ( SeDBP ) of 100 to 115 mm Hg were r and omized to one of 12 groups :  placebo , olmesartan medoxomil monotherapy ( 10 , 20 , or 40 mg/day , HCTZ monotherapy ( 12.5 or 25 mg/day ) , or one of six groups of olmesartan medoxomil/HCTZ combination therapy . The primary endpoint was the change in mean trough SeDBP from baseline at week 8 . Statistical analyses were conducted to determine whether at least one combination produced a larger reduction in SeDBP at week 8 than the individual corresponding component doses , but did not compare BP reductions with different combination doses . RESULTS Olmesartan medoxomil plus HCTZ produced greater reductions in both SeDBP and seated systolic blood pressure ( SeSBP ) at week 8 than did monotherapy with either component . All olmesartan medoxomil/HCTZ combinations significantly reduced SeDBP and SeSBP compared with placebo in a dose-dependent manner . Reductions from baseline in mean trough SeSBP/SeDBP were 3.3/8.2 mm Hg , 20.1/16.4 mm Hg , and 26.8/21.9 mm Hg with placebo , olmesartan medoxomil/HCTZ 20/12.5 mg , and olmesartan medoxomil/HCTZ 40/25 mg , respectively . All treatments were well tolerated . CONCLUSIONS Olmesartan medoxomil/HCTZ combination therapy produced BP reductions of up to 26.8/21.9 mm Hg and 
    Output:
    
agent
The effect was similar to that obtained when thiazides are used as a single agent .
Thiazides when given as a second-line drug have a dose related effect to lower blood pressure that is similar to when they are added as a first-line drug .
This means that the BP lowering effect of thiazides is additive .
Loop diuretics appear to have a similar blood pressure lowering effect as thiazides at 1 times the recommended starting dose .
Because of the short duration of the trials and lack of reporting of adverse events , this review does not provide a good estimate of the incidence of adverse effects of diuretics given as a second-line drug
***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: A multicentre , r and omised , placebo-controlled parallel group study comparing various doses of the combination diltiazem SR ( DTZ SR)/hydrochlorothiazide ( HCTZ ) with the monotherapies was performed to delineate the optimal antihypertensive dosage of the two drug combinations . The study was carried out in 298 patients with mild to moderate essential hypertension ( stable supine diastolic blood pressure , DBP , greater than or equal to 95 and less than or equal to 110 mmHg ) . After a single-blind placebo lead-in period lasting 4 - 6 weeks to establish stable baseline BP , the patients were r and omised to receive either placebo ( n = 75 ) , HCTZ ( n = 76 ) , DTZ SR ( n = 72 ) , or the combination of DTZ SR/HCTZ ( n = 75 ) . There were three 4-week evaluation periods with forced escalation of therapy as follows : HCTZ ( 6.25 , 6.25 , 12.5 mg twice daily ) , DTZ SR ( 60 , 90 , 120 mg twice daily ) , and the combination of DTZ SR/HCTZ ( 60/6.25 , 90/6.25 , 120/12.5 mg twice daily ) . DTZ SR/HCTZ ( 120/12.5 mg ) produced statistically significantly greater reductions in supine DBP compared with each monotherapy and placebo . The lower doses of DTZ SR/HCTZ ( 60/6.25 mg and 90/6.25 mg ) produced statistically significantly greater supine DBP reductions compared with DTZ SR monotherapy and placebo , but not compared with HCTZ monotherapy . A comparison of reduction in supine DBP between evaluation periods demonstrated a dose-response relationship for the combination therapy in reducing BP over the dosage range studied . Adverse clinical and laboratory events were not significantly different between the therapies . ( ABSTRACT TRUNCATED AT 250 WORDS BACKGROUND AND PURPOSE Converting enzyme inhibition and calcium blockade alter large arteries in hypertension . However , the heterogeneity of the response according to the site of cardiovascular measurements has never been investigated . METHODS In a double-blind study , we compared for 180 days 3 hypertensive patient groups treated with verapamil , tr and olapril , or their combination .  Using echo-Doppler technique and applanation tonometry , we independently measured mean pressure , local pulse pressure , arterial diameter , and distensibility at 3 arterial sites ( brachial and common carotid arteries and abdominal aorta ) , as well as cardiac and carotid wall structure . RESULTS Mean and pulse pressure decreased significantly to a greater extent with the drug combination . Regarding arterial and cardiac hemodynamics , significant and similar changes were noted in the 3 groups : decreases in abdominal aorta and carotid but not brachial diameter ; increases in carotid artery , abdominal aorta , and brachial distensibility even after adjustment to mean blood pressure reduction ; and more substantial regression of cardiac mass than carotid wall thickness . CONCLUSIONS This study shows that both compounds and more significantly combination therapy decreased mean and pulse pressures measured independently and that the changes in diameter , thickness , and stiffness were influenced primarily by the site of cardiovascular measurements , result ing in a predominant increase in distensibility of muscular arteries , little change in carotid wall thickness , but a significant regression of cardiac hypertrophy The efficacy and safety of enalapril and hydrochlorothiazide was investigated in a multicenter study of 81 patients with mild to moderate essential hypertension . The subjects were r and omly assigned to one of three groups and , following a placebo period , given enalapril maleate ( 20 mg ) , hydrochlorothiazide ( 12.5 mg ) , or a combination of the two drugs ( 32.5 mg ) . A significant decrease in blood pressure was observed after only 2 weeks in the enalapril and enalapril-hydrochlorothiazide groups . A double dose was required to achieve a satisfactory response in one-third of the patients in both the enalapril ( 9 of 27 ) and the enalapril-hydrochlorothiazide groups ( 8 of 27 ) . Adverse reactions included cough in one patient and mild hyperkalemia in another , both of whom received enalapril . Two patients on the drug combination developed side effects -- symptomatic orthostatic hypotension in one and impotence in the second . Enalapril alone and in combination with hydrochlorothiazide appears to be effective and well tolerated The efficacy , tolerability and metabolic effects of a fixed combination of lisinopril 10 mg and hydrochlorothiazide 12.5 mg ( L/HCTZ ) and those of the monocomponents were compared in 286 mild to moderate hypertensive patients in a 17-centre study using a double-blind , r and omized , parallel-group design . After 2 weeks of placebo run-in , patients were r and omized to one of the three treatments for 8 weeks . Supine and st and ing BPs were measured at peak blood levels ( 4 - 8 hours post dose ) after 4 weeks , and at trough blood levels ( 24 - 28 hours post dose ) after 8 weeks . The BP reduction from baseline was greater with L/HCTZ than with the monocomponents at weeks 4 and 8 ; at week 8 the reduction was statistically significant vs lisinopril for st and ing DBP ( P less than 0.027 ) but not for st and ing SBP ; the reduction was significant with L/HCTZ vs hydrochlorothiazide at week 4 [ P = 0.0002/0.0001 ( SBP/DBP ) supine ; P = 0.0002/0.0002 st and ing ] and at week 8 ( P = 0.0001/0.0001 supine and st and ing ) . Response at week 8 ( supine DBP less than or equal to 90 mm Hg ) with L/HCTZ ( 87.0 % ) was greater than with hydrochlorothiazide ( 29.0 % ; P less than 0.0001 ) and marginally greater than with lisinopril ( 74.2 % ; P = 0.069 ) . Heart rate fell statistically significantly more with L/HCTZ ( by 3.3 beats/minute ) than with HCTZ ( by 0.86 beats/minute ; P = 0.018 ) . L/HCTZ treatment significantly increased plasma uric acid levels compared with lisinopril . L/HCTZ decreased potassium , while lisinopril  increased potassium . L/HCTZ decreased cholesterol ; HCTZ increased it . Adverse effects were more common on L/HCTZ vs lisinopril ( P = 0.033 ) but not vs hydrochlorothiazide . ( ABSTRACT TRUNCATED AT 250 WORDS Summary The efficacy of cilazapril monotherapy and in combination with hydrochlorothiazide 12.5 mg was compared in a multicentre , double blind , r and omised parallel group study in 87 patients with mild to moderate essential hypertension over 8 weeks . After a 2 week single blind placebo run-in period , patients received either 2.5 mg cilazapril or 2.5 mg cilazapril plus 12.5 mg hydrochlorothiazide once daily . At Week 4 the cilazapril dose was increased from 2.5 mg to 5.0 mg if the mean sitting diastolic blood pressure was greater than 90 mmHg or had not decreased by more than 10 mmHg . After 8 weeks treatment 72 % of patients responded to 2.5 mg cilazapril increasing to 88 % with cilazapril 5.0 mg . For cilazapril plus hydrochlorothiazide , 83 % responded to 2.5 mg cilazapril increasing to 96 % on 5.0 mg cilazapril . The high response rate to low dose cilazapril monotherapy and hydrochlorothiazide combination therapy has important implication s for minimising the cost of therapy with ACE inhibitors Two hundred and eleven patients with mild or moderate hypertension , mean age 53.5 + /- 9.5 years ( range 24 - 70 ) were r and omised double-blind to treatment with either captopril 50 mg ( C50 ) , hydrochlorothiazide 25 mg ( HCTZ 25 ) , the fixed combination of captopril 50 mg and hydrochlorothiazide 25 mg ( C50/HCTZ 25 ) or placebo .  Blood pressure , heart rate , body weight and side effects were assessed at the end of the run-in period on placebo and after 4 , 6 , 8 weeks treatment at the same time , 20 - 24 h after the last dosing . Routine biochemical examinations were carried out on all patients after the placebo period as well as after 4 and 8 weeks . Blood pressure significantly decreased in all groups , but the mean percentage change from baseline was highly statistically significant at 8 weeks , for C50 and C50/HCTZ 25 groups . The incidence of clinical side effects was low and not statistically different for the four groups with few specific adverse effects ( one transient alteration of taste in captopril group ) . No patient was withdrawn from the study due to side effects . A better anti-hypertensive efficacy was obtained with the fixed combination captopril 50 mg/hydrochlorothiazide 25 mg once daily compared to placebo or each component alone , and without any difference in side effects Summary : In an 8-week , double-blind , r and omized , active-controlled , multicenter study with three parallel treatment groups , we compared the efficacy and safety of once-daily 20 mg quinapril plus 12.5 mg hydrochlorothi-azide ( HCTZ ) with each drug as monotherapy in patients with moderate to severe hypertension . Hypertensive out patients with supine diastolic blood pressure ( DBF ) ≤105 and ≥120 mm Hg at the end of a 2− to 4-week placebo-baseline period were r and omly assigned to one of the treatment groups . Of the 323 patients who were r and omized to double-blind medication , 297 completed the study , but 6 patients were excluded for violations of protocol ; therefore , statistical analysis was performed in 291 patients . Only 7 patients withdrew owing to lack of efficacy ( 2 receiving combination therapy ) . In all three treatment groups , clinical ly significant reductions in DBF were achieved . Combination therapy was statistically more effective than each component in both evaluable data and intent-to-treat analyses . The incidence of adverse events ( AE ) was 24 % in the quinapril monotherapy group , 14 % in the combination therapy group , and 11 % in the HCTZ monotherapy group . Orthostatic hypotension with related symptoms was observed in 4 patients ( 2 receiving quinapril monotherapy , 1 receiving HCTZ monotherapy , and 1 receiving combination therapy ) . Once-daily quinapril plus HCTZ provided increased reduction of DBF as compared with the monotherapies and was well tolerated in patients with moderate to severe hypertension BACKGROUND Most patients with hypertension require more than one agent to control blood pressure ( BP ) . The purpose of this study was to assess the efficacy and safety of the angiotensin II receptor blocker olmesartan medoxomil in combination with hydrochlorothiazide ( HCTZ ) . METHODS This was a r and omized , double-blind , factorial design study . After a placebo run-in period , eligible patients ( n = 502 ) with a baseline mean seated diastolic blood pressure ( SeDBP ) of 100 to 115 mm Hg were r and omized to one of 12 groups :  placebo , olmesartan medoxomil monotherapy ( 10 , 20 , or 40 mg/day , HCTZ monotherapy ( 12.5 or 25 mg/day ) , or one of six groups of olmesartan medoxomil/HCTZ combination therapy . The primary endpoint was the change in mean trough SeDBP from baseline at week 8 . Statistical analyses were conducted to determine whether at least one combination produced a larger reduction in SeDBP at week 8 than the individual corresponding component doses , but did not compare BP reductions with different combination doses . RESULTS Olmesartan medoxomil plus HCTZ produced greater reductions in both SeDBP and seated systolic blood pressure ( SeSBP ) at week 8 than did monotherapy with either component . All olmesartan medoxomil/HCTZ combinations significantly reduced SeDBP and SeSBP compared with placebo in a dose-dependent manner . Reductions from baseline in mean trough SeSBP/SeDBP were 3.3/8.2 mm Hg , 20.1/16.4 mm Hg , and 26.8/21.9 mm Hg with placebo , olmesartan medoxomil/HCTZ 20/12.5 mg , and olmesartan medoxomil/HCTZ 40/25 mg , respectively . All treatments were well tolerated . CONCLUSIONS Olmesartan medoxomil/HCTZ combination therapy produced BP reductions of up to 26.8/21.9 mm Hg and 
    Output:
    