Effect of telmisartan/hydrochlorothiazide combination versus nifedipine GITS on ambulatory blood pressure and sympathetic activation. Antihypertensive effects of two fixed-dose combinations of losartan and hydrochlorothiazide versus hydrochlorothiazide monotherapy in subjects with ambulatory systolic hypertension. Low dose hydrochlorothiazide (12.5 to 25 mg daily) as monotherapy in black patients with mild to moderate hypertension. Assessment by ambulatory blood pressure monitoring. [The additional efficacy of the nifedipine-diuretic combination depends on the potency of the drug administered first and not the sequence of administration. A double blind study in salt-sensitive black hypertensives]. Antihypertensive effects of amlodipine and hydrochlorothiazide in elderly patients with ambulatory hypertension. Antihypertensive effect of low-dose hydrochlorothiazide alone or in combination with quinapril in black patients with mild to moderate hypertension. A home blood pressure monitoring study comparing the antihypertensive efficacy of two angiotensin II receptor antagonist fixed combinations. Expedited blood pressure control with initial angiotensin II antagonist/diuretic therapy compared with stepped-care therapy in patients with ambulatory systolic hypertension. Efficacy and safety of fosinopril/hydrochlorothiazide combinations on ambulatory blood pressure profiles in hypertension. Fosinopril/Hydrochlorothiazide Investigators. Antihypertensive Effects of Valsartan/Hydrochlorothiazide Combination in Essential Hypertension Comparison of office, ambulatory, and home blood pressure antihypertensive response to atenolol and hydrochlorthiazide. Effects of valsartan/ hydrochlorothiazide and amlodipine on ambulatory blood pressure and plasma norepinephrine levels in high-risk hypertensive patients Evaluation of antihypertensive therapy with the combination of olmesartan medoxomil and hydrochlorothiazide. Comparative effectiveness of a fixed-dose combination of losartan + HCTZ versus bisoprolol + HCTZ in patients with moderate-to-severe hypertension: results of the 6-month ELIZA trial Matrix study of irbesartan with hydrochlorothiazide in mild-to-moderate hypertension. Effect of telmisartan/hydrochlorothiazide vs lisinopril/hydrochlorothiazide combination on ambulatory blood pressure and cognitive function in elderly hypertensive patients Controlled Multicenter Study of the Antihypertensive Effects of Lisinopril, Hydrochlorothiazide, and Lisinopril plus Hydrochlorothiazide in the Treatment of 394 Patients with Mild to Moderate Essential Hypertension Renin inhibition with aliskiren provides additive antihypertensive efficacy when used in combination with hydrochlorothiazide Efficacy of Low-Dose Hydrochlorothiazide in Combination with Telmisartan on Early Morning Blood Pressure in Uncontrolled Hypertensive Patients Nocturnal reduction of blood pressure and the antihypertensive response to a diuretic or angiotensin converting enzyme inhibitor in obese hypertensive patients. TROPHY Study Group. Monotherapy with amlodipine or hydrochlorothiazide in patients with mild to moderate hypertension: Comparison of their efficacy and effects on electrolytes Freehand three-dimensional echocardiographic evaluation of the effect of telmisartan compared with hydrochlorothiazide on left ventricular mass in hypertensive patients with mild-to-moderate hypertension: a multicentre study Triple Antihypertensive Therapy With Amlodipine, Valsartan, and Hydrochlorothiazide: A Randomized Clinical Trial Efficacy and safety of two treatment combinations of hypertension in very elderly patients. Antihypertensive efficacy and tolerability of captopril in the elderly: comparison with hydrochlorothiazide and placebo in a multicentre, double-blind study. Impact of angiotensin receptor blockade in combination with hydrochlorothiazide 25 mg in 2121 patients with stage 1–2 hypertension Increased efficacy and tolerability with losartan plus hydrochlorothiazide in patients with uncontrolled hypertension and therapy-related symptoms receiving two monotherapies. Olmesartan/amlodipine/hydrochlorothiazide in participants with hypertension and diabetes, chronic kidney disease, or chronic cardiovascular disease: a subanalysis of the multicenter, randomized, double-blind, parallel-group TRINITY study Zofenopril Plus Hydrochlorothiazide and Irbesartan Plus Hydrochlorothiazide in Previously Treated and Uncontrolled Diabetic and Non-diabetic Essential Hypertensive Patients A dose escalation trial comparing the combination of diltiazem SR and hydrochlorothiazide with the monotherapies in patients with essential hypertension. Rationale and design for the Controlled ONset Verapamil INvestigation of Cardiovascular Endpoints (CONVINCE) Trial. Controlled trial of losartan given concomitantly with different doses of hydrochlorothiazide in hypertensive patients. Telmisartan plus hydrochlorothiazide versus telmisartan or hydrochlorothiazide monotherapy in patients with mild to moderate hypertension: a multicenter, randomized, double-blind, placebo-controlled, parallel-group trial. A randomized, controlled trial comparing diltiazem, hydrochlorothiazide, and their combination in the therapy of essential hypertension.
BACKGROUND This study compares the effects of telmisartan hydrochlorothiazide ( HCTZ ) combination versus nifedipine GITS on ambulatory blood pressure ( BP ) and sympathetic activity , in patients with mild-to-moderate hypertension . METHODS One hundred twenty-four out patients with sitting diastolic BP > or = 95 mmHg and < 110 mm Hg were r and omized to telmisartan 80 mg/HCTZ 12.5 mg daily ( n = 62 ) or nifedipine GITS 60 mg daily ( n = 62 ) for 12 weeks , according to a prospect i ve , open-label , blind end point , parallel-group design . At the end of a 2-week washout period and after 12 weeks of active treatment , 24-h noninvasive ambulatory BP monitoring  ( ABPM ) was performed , clinic BP and heart rate were measured , and plasma norepinephrine and cardiovascular responses to mental stress induced by the color word test were assessed . RESULTS Both treatments reduced ambulatory and clinic BP . However , the drug combination had an antihypertensive efficacy significantly greater than nifedipine GITS , as shown by the 24-h ( P < .001 ) , daytime ( P < .001 ) , and night-time ( P < .01 ) ambulatory BP monitoring values , as well as by the clinic BP at trough ( P < .05 ) . The trough-to-peak ratio was similar , but the smoothness index was significantly higher with the combination for both systolic and diastolic BP ( P < .05 ) . A significant increase in plasma norepinephrine levels in resting conditions was observed with nifedipine GITS ( + 20 % ) but not with telmisartan/HCTZ combination . The color word test produced a greater increase in plasma norepinephrine and heart rate values in the patients treated with nifedipine GITS than in those treated with the combination . CONCLUSIONS These results suggest that the telmisartan 80 mg/HCTZ 12.5 mg combination provided a more sustained and homogeneous BP control than nifedipine GITS 60 mg , without producing sympathetic activation BACKGROUND The efficacy of losartan ( L ) in combination with hydrochlorothiazide ( HCTZ ) has been demonstrated to reduce blood pressure . However , there are limited data on the effects of L/HCTZ combinations versus HCTZ monotherapies in reducing ambulatory systolic blood pressure . The aim of this study was to compare the effects of these treatment approaches in patients with ambulatory systolic hypertension . METHODS Patients were r and omized to receive L 50 mg ( n = 60 ) or HCTZ 12.5 mg ( n = 60 ) for 6 weeks . Patients were then force-titrated to L 50/HCTZ 12.5 mg and to L 100/HCTZ 25 mg or were sham-titrated to HCTZ 12.5 mg and force-titrated to HCTZ 25 mg , respectively . Clinic and 24-h ambulatory blood pressure ( ABP ) were measured at baseline and after each 6-week treatment period . RESULTS We found that L 50 and HCTZ 12.5 induced significant and similar decreases in clinic and ABP . The combinations of L 50/HCTZ 12.5 and L 100/HCTZ 25 provided significantly greater decreases in clinic and ABP than did HCTZ monotherapies . The L 50/HCTZ 12.5 and L 100/HCTZ 25 combinations provided significant additional decreases in systolic/diastolic ABP during daytime ( -5.3/-2.0 mm Hg ; P < .001 and -5.8/-3.4 mm Hg ; P < .001 ) and the other periods of the 24-h interval compared with the levels achieved by the previous treatment , indicating a clear dose-response relationship . However , increasing the dose of HCTZ from 12.5 mg to 25 mg was not associated with additional ABP reductions . CONCLUSIONS Combinations of L 50/HCTZ 12.5 and L 100/HCTZ 25 provided greater reductions in clinic and ABP than HCTZ monotherapies , with a clear dose-response relationship with regard to ABP . These results support the use of ABP monitoring when assessing the efficacy of antihypertensive therapies The efficacy of low dose ( 12.5 to 25 mg daily ) hydrochlorothiazide ( HCTZ ) was evaluated by ambulatory blood pressure monitoring ( ABPM ) in 19 mild to moderate hypertensive ( mean daytime 12-h diastolic BP > or = 90 mm Hg and < 115 mm Hg ) South African black patients . After a 3-week placebo run-in period , HCTZ was administered for 8 weeks as monotherapy . The mean daytime ABPM was reduced from 159 + /- 13/105 + /- 6 to 145 + /- 11/97 + /- 10 mm Hg ( P < .005 ) . Only 6/19 ( 32 % ) patients achieved BP control . The 24-h BP load fell from 69 % at baseline , to 53 % with 12.5 mg HCTZ and to 47 % with 25 mg HCTZ daily . There were no side effects but the increase of HCTZ to 25 mg daily was followed by adverse changes ( P < .05 ) in serum potassium levels . It is concluded that low dose of HCTZ monotherapy has only a moderate effect on the BP control and 24-h BP load while the higher 25 mg dose is associated with significant decrease in serum potassium level OBJECTIVE To evaluate whether the additional antihypertensive efficacy of the nifedipine-thiazide combination depends on the sequence of drug administration and whether the natriuretic effect of thiazide persists when co-administered with nifedipine . METHODS Double blind , r and omised , crossover , placebo-controlled study , in 12 salt-sensitive hypertensive black patients ( SSH ) . Evaluation of the antihypertensive ( 24 h ambulatory monitoring ) and natriuretic effects of placebo ( PL ) , of nifedipine-GITS ( NIF , 30 mg/d ) and of hydrochlorothiazide ( HCTZ , 25 mg/d ) given alone and in combination within two separate therapeutic sequences : PL-->NIF-->NIF + HCTZ and PL-->HCTZ-->HCTZ + NIF ( 1 month for each therapeutic regimen ) . RESULTS NIF induced greater ( p < 0.04 ) reduction of 24 h mean arterial pressure ( MAP ) ( -15.9 + /- 1.9 mm Hg , v PL ) than HCTZ ( -9.0 + /- 1.3 mm Hg ) . The association of NIF to HCTZ induced a greater ( p < 0.05 ) additional reduction of MAP-24 h ( 9.7 + /- 2.2 mm Hg ) than that produced by the association of HCTZ to NIF ( 4.1 + /- 1.3 mm Hg ) . NIF alone and in combination did not modify the diuresis-natriuresis observed with the previous treatment , whereas HCTZ alone and in combination always increased diuresis ( by 25 % ) and natriuresis ( by 53 % ) . There was a significant negative correlation ( r = -0.71 , p < 0.001 ) between blood pressure ( BP ) reduction induced by the drug administered first ( NIF or HCTZ ) and the additional BP reduction obtained by the association of the second drug . CONCLUSIONS In most of the SSH the NIF-GITS was more potent than HCTZ . NIF did not modify the diuretic-natriuretic effect of PL and of HCTZ . The greater potency of NIF may explain why in most patients the combination HCTZ to NIF induced a lower hypotensive effect than that of the association of NIF to HCTZ . Independently of the sequence of the drug administration , the lower the hypotensive effect of the drug administered first the greater the additional hypotensive effect that was observed by adding the second drug Recent studies and authorities have advocated the use of low-dose thiazide diuretics as first-line treatment agents in elderly hypertensives . However , these recommendations were based solely on blood pressure ( BP ) measured in the clinic . The objective of the present 32-week double-blind study was to compare the effects of hydrochlorothiazide ( HCTZ ) and amlodipine ( AML ) in elderly patients with confirmed ambulatory hypertension . After a 4-week placebo washout period , 42 ( 25 men , 17 women ) patients ( mean age , 69 years ) with clinic sitting diastolic BP of 95 to 114 mm Hg and daytime ambulatory diastolic BP of > or = 90 mm Hg were r and omized double-blind to receive AML 5 to 10 mg ( n = 21 ) or HCTZ 12.5 to 25 mg ( n = 21 ) once daily . After 8 weeks of monotherapy , patients in whom clinic diastolic BP remained > or = 90 mm Hg were given combination therapy with the other agent . Amlodipine monotherapy induced significant reductions in clinic , mean 24-h , daytime and sleep systolic/diastolic BPs whereas only clinic BP decreased significantly in patients treated with HCTZ monotherapy . Moreover , 19/21 versus 8/21 patients on AML and HCTZ monotherapies achieved adequate BP control . At the end of the 32-week treatment period , combination therapy in the HCTZ group result ed in statistically significant reductions in clinic as well as in 24-h , daytime and sleep ambulatory BPs that were similar to those observed in the AML monotherapy group . In conclusion , the administration of AML monotherapy induced significant reductions in both clinic and ambulatory BPs in elderly patients whereas only clinic BP was significantly decreased by HCTZ monotherapy . Moreover , the addition of AML to HCTZ in patients inadequately controlled by monotherapy has permitted statistically significant decrements in clinic as well as in ambulatory BP . Consequently , the results of the present study suggest that the use of HCTZ in doses of up to 25 mg daily is inadequate for ambulatory BP control in the elderly despite official recommendations In this study , using 24-hour ambulatory blood pressure ( BP ) monitoring , the authors assessed the potential for BP control using hydrochlorothiazide ( HCTZ , 12.5 mg daily ) , given as a monotherapy over 12 months to 49 black South African patients with mild to moderate hypertension ( mean day diastolic blood pressure [ DBP ] > or = 90 and < 115 mmHg ) . Uncontrolled patients received fixed combination of quinapril/HCTZ 10/12.5 , 20/12.5 , and 20/25 mg , with dose titration at 3 monthly intervals if BP control was not achieved ( day DBP < 90 mmHg ) . Overall , profound and sustained BP reduction was observed at the end of the study . The 24-hour BP decreased from 151 + /- 14/98 + /- 7 to 136 + /- 15/87 + /- 9 mmHg ( p < 0.0001 at end of study vs. baseline ) ; the mean day BP decreased from 155 + /- 14/104 + /- 7 to 140 + /- 15/91 + /- 10 mmHg ( p < 0.0001 at end of study vs. baseline ) . The overall control ( mean day DBP < 90 mmHg ) and response ( decrease in day DBP > or = 10 mmHg ) rates were 49 % and 61 % , respectively . At the end of the study , only 2 patients ( 4 % ) remained on treatment with HCTZ . Out of the initial 12 patients controlled on HCTZ at 3 months ( 12/49 , 24 % ) , 5 patients remained controlled at 6 months and only 1 patient at 12 months . In contrast , quinapril/HCTZ combinations maintained their antihypertensive effect up to 9 months , with a significant number of patients ( 22/49 , 45 % ) requiring the highest dose of the combination ( 20/25 mg daily ) . In conclusion , low-dose HCTZ should not be recommended as monotherapy in black patients with mild to moderate hypertension due to the fact that the BP-lowering effect is attenuated already at 6 months of treatment , with most patients requiring the addition of the ACE inhibitor BACKGROUND The objective of this prospect i ve , r and omized , open-label , blinded-endpoint study was to compare the antihypertensive efficacy of valsartan 80 mg v irbesartan 150 mg when combined with hydrochlorothiazide ( HCTZ ) 12.5 mg . METHODS Untreated or uncontrolled hypertensive adults ( n = 800 ) were enrolled by primary care physicians . After a 5-week open-label lead-in phase in which all patients received 12.5 mg HCTZ once daily , subjects whose blood pressure ( BP ) remained uncontrolled were r and omized ( n = 464 ) to valsartan/HCTZ ( 80/12.5 mg ) or irbesartan/HCTZ ( 150/12.5 mg ) for 8 weeks .  Home BP monitoring ( HBPM ) was performed in the morning and in the evening for 5 days , at baseline , and after 8 weeks . Office BP measurements were obtained at baseline and after 8 weeks . RESULTS Irbesartan/HCTZ produced greater reductions in average systolic BP ( SBP ) and diastolic BP ( DBP ) measured by HBPM than valsartan/HCTZ ( SBP : -13.0 v -10.6 mm Hg , P = .0094 ; DBP : -9.5 v -7.4 mm Hg , P = .0007 ) . These differences were more pronounced in the morning ( trough ) than in the evening . Office BP measurements also showed greater reductions in trough seated SBP and DBP with irbesartan/HCTZ compared with valsartan/HCTZ . Normalization rates observed with HBPM ( SBP < 135 mm Hg and DBP < 85 mm Hg ) were significantly greater with irbesartan/HCTZ than with valsartan/HCTZ ( 50.2 v 33.2 % ; P = .0003 ) . The overall safety was similar in the two groups . CONCLUSIONS The superior BP-lowering potency of the fixed combination irbesartan/HCTZ ( 150/12.5 mg ) over valsartan/HCTZ ( 80/12.5 mg ) , evidence d independently from the investigators by HBPM , supports the use of this technique in trials with prospect i ve , r and omized , open-label , blinded-endpoint design OBJECTIVES The present study investigated whether initiating therapy with a combination of losartan ( L ) and hydrochlorothiazide ( HCTZ ) allows for faster blood pressure ( BP ) control and fewer medications than the usual stepped-care approach in patients with stage 2 or 3 hypertension and ambulatory systolic hypertension . METHODS Patients with a mean daytime systolic ambulatory BP ( ABP ) of 135 mmHg or higher were r and omly assigned to receive L 50 mg plus HCTZ 12.5 mg titrated to L 100 mg plus HCTZ 25 mg versus HCTZ 12.5 mg plus atenolol 50 mg . Amlodipine 5 mg was then added , if needed , to achieve a  BP goal of less than 130 mmHg . Treatment titration was based on ABP . RESULTS Significantly more patients r and omly assigned to L/HCTZ ( 63.5 % ) than stepped-care ( 37.5 % ; P=0.008 ) achieved the primary end point ( daytime systolic BP of less than 130 mmHg ) . Initial L/HCTZ induced significantly greater decreases in ABP during each 24 h period after six weeks of therapy . Although reductions in systolic and diastolic ABP were not statistically different at the end of the study , ABP reduction was significantly greater ( P<0.001 ) with the L/HCTZ-based regimen . Twice as many patients in the L/HCTZ group achieved the goal ABP with no more than two drugs ( 30.0 % versus 14.7 % ; P=0.03 ) . Moreover , tolerability was significantly better ( P=0.006 ) in the L/HCTZ group , with a 40.0 % incidence of adverse events , versus 65.6 % in the stepped-care group . CONCLUSION Initiating antihypertensive therapy with the combination of L/HCTZ in patients with stage 2 or 3 hypertension and ambulatory systolic hypertension reaches a target BP faster in a higher proportion of patients , with fewer adverse events and less need for a third drug regimen than the conventional stepped-care approach Twenty-four-hour ambulatory blood pressure monitoring ( ABPM ) was used to assess the antihypertensive efficacy and safety of the angiotensin converting enzyme ( ACE ) inhibitor fosinopril ( Fos ) in combination with hydrochlorothiazide ( HCTZ ) in doses of 10/12.5 mg and 20/12.5 mg taken once daily versus placebo in patients with mild-to-moderate hypertension . In two method ologically identical studies , the antihypertensive effects were evaluated by 24-h ABPM and by seated office diastolic ( DBP ) and systolic ( SBP ) blood pressures . After a 4- or 5-week placebo washout , 79 patients received r and omized , double-blind treatment for 8 weeks with either the Fos/HCTZ 10/12.5-mg dose combination ( n = 41 ) or placebo ( n = 38 ) , and in the second study , 62 patients were treated with either the Fos/HCTZ 20/12.5-mg dose combination ( n = 30 ) or placebo ( n = 32 ) . Changes from baseline in mean 24-h systolic and diastolic ABPM were significantly different from placebo for both doses ( SBP/DBP with 10/12.5 mg , -18.2/ -10.1 mm Hg , P < or= .001 ; SBP/DBP with 20/12.5 mg , -22.9/ -11.2 mm Hg , P < or= .001 ) ; whereas ambulatory SBP and DBP in the placebo group were virtually unchanged . Although the antihypertensive effect of the higher Fos/HCTZ dose combination ( 20/12.5 mg ) appeared greater than the lower dose ( 10/12.5 mg ) , no attempt was made to make a comparison between the two doses over these two independent studies . This difference in blood pressure lowering was not reproduced by the office blood pressure readings . Both dose combinations of Fos/HCTZ produced significantly greater reductions in the office seated DBP than placebo at all time points tested with a maximum treatment effect ( drug effect - placebo effect ) of -7.3 mm Hg for the 10/12.5-mg dose and -8.2 mm Hg for the 20/12.5-mg dose after 8 weeks of therapy ( P < or= .01 ) . Based on the results obtained in these trials , both dose combinations of Fos/HCTZ taken once daily were safe and effective in the management of patients with mild-to-moderate hypertension . Twenty-four-hour ABPM detected what appears to be an enhanced blood pressure reduction with the higher Fos/HCTZ dose combination ( 20/12.5 mg ) at peak and trough , which was not reproduced by trough office blood pressure measurements , suggesting greater sensitivity of 24-h ABPM for evaluating antihypertensive effects Fixed-dose combination therapy has received increased interest since publication of JNC-VI report and WHO/ISH guidelines 1999 . We compared in a r and omized , double-blind study the efficacy and tolerability of valsartan 80 mg combined with hydrochlorothiazide ( HCTZ ) 12.5 mg to monotherapy with either HCTZ 12.5 mg or 25 mg in patients with essential hypertension inadequately controlled by previous HCTZ 12.5 mg monotherapy . Two hundred and seventeen patients whose blood pressure ( BP ) control remained poor ( 95 mmHg h sitting diastolic BP < 115 mmHg ) after a 4-week single-blind period with HCTZ 12.5 mg were r and omized to receive either combination therapy with valsartan 80 mg plus HCTZ 12.5 mg ( V/HCTZ ) or monotherapy with HCTZ 12.5 mg or HCTZ 25 mg for 8 weeks . Reduction of sitting trough diastolic BP between baseline and week 8 as well as tolerability was evaluated . Reduction in trough diastolic BP was most pronounced in the V/HCTZ group ( –11.3 mmHg ) and significantly greater than in the HCTZ 12.5 mg group ( –2.9 mmHg , p < 0.001 ) and the HCTZ 25 mg group ( –5.7 mmHg , p < 0.001 ) . Tolerability of study medication was comparable between all three groups . In conclusion , switching to V/HCTZ combination therapy provides an additional lowering of BP compared to dosage increase of the thiazide in patients with BP insufficiently controlled by HCTZ 12.5 mg monotherapy Office , home , and ambulatory blood pressure ( BP ) demonstrate variable associations with outcomes . The authors sought to compare office BP ( OBP ) , home BP ( HBP ) , and ambulatory BP ( ABP ) for measuring responses to hydrochlorothiazide ( HCTZ ) , atenolol , and their combination . After completing washout , eligible patients were r and omized to atenolol 50 mg or HCTZ 12.5 mg daily . Doses were doubled after 3 weeks and the alternate drug was added after 6 weeks if BP was > 120/70 mm Hg ( chosen to allow maximum opportunity to assess genetic associations with dual BP therapy in the parent study ) .  OBP  ( in triplicate ) ,  HBP  ( twice daily for 5 days ) , and 24-hour ABP  were measured at baseline , after monotherapy , and after combination therapy . BP responses were compared between OBP , HBP , and ABP for each monotherapy and combination therapy . In 418 patients , OBP overestimated BP response compared with HBP , with an average 4.6 mm Hg greater reduction in systolic BP ( P<.0001 ) and 2.1 mm Hg greater reduction in diastolic BP ( P<.0001 ) across all therapies . Results were similar for  atenolol  and  HCTZ monotherapy . ABP response was more highly correlated with HBP response ( r=0.58 ) than with OBP response ( r=0.47 ; P=.04 ) . In the context of a r and omized clinical trial , the authors have identified significant differences in HBP , OBP , and ABP methods of measuring BP response to atenolol and HCTZ monotherapy 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 160 mg and HCTZ 12.5 mg provides more sustained and homogeneous control of blood pressure than does amlodipine 10 mg in high-risk hypertensive patients , without producing reflex sympathetic activation 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 was well tolerated Background The aim of this study was to compare the antihypertensive efficacy of losartan 100 mg + hydrochlorothiazide ( HCTZ ) 25 mg versus bisoprolol 10 mg + HCTZ 25 mg and their influence on arterial stiffness and central blood pressure ( BP ) . Methods Of 60 patients with a mean BP of 173.3 ± 1.7/98.4 ± 1.2 mmHg , 59 were r and om-ized to losartan + HCTZ ( n = 32 ) or bisoprolol + HCTZ ( n = 27 ) .  Amlodipine was added if target BP was not achieved at 1 month , and doxazosin was added if target BP was not achieved after 3 months . Body mass index , office and 24-hour ambulatory BP , pulse wave velocity ( carotid-femoral [ PWVE ] and radial [ PWVM ] ) , noninvasive central systolic BP , augmentation index ( AIx ) , laboratory investigations , and electrocardiography were done at baseline and after 6 months of treatment . Results Losartan + HCTZ was as effective as bisoprolol + HCTZ , with target office BP achieved in 96.9 % and 92.6 % of patients and target 24-hour BP in 75 % and 66.7 % of patients , respectively , after 6 months . Effective treatment of BP led to significant lowering of central systolic BP , but this was decreased to a significantly ( P < 0.05 ) greater extent by losartan + HCTZ ( −23.0 ± 2.3 mmHg ) than by bisoprolol + HCTZ ( −15.4 ± 2.9 mmHg ) despite equal lowering of brachial BP . Factors correlated with central systolic BP and its lowering differed between the treatment groups . Losartan + HCTZ did not alter arterial stiffness patterns significantly , but bisoprolol + HCTZ significantly increased AIx . We noted differences in ΔPWVE , ΔPWVM , and ΔAIx between the groups in favor of losartan + HCTZ . Decreased heart rate was associated with higher central systolic BP and AIx in the bisoprolol + HCTZ group , but was not associated with increased AIx in the losartan + HCTZ group . Conclusion Although both treatments decreased both office and 24-hour BP  , losartan + HCTZ  significantly decreased central systolic BP and had a more positive influence on pulse wave velocity , with a less negative effect of decreased heart rate on AIx and central systolic BP The purpose of this study was to assess the safety and antihypertensive dose-response effects of irbesartan and hydrochlorothiazide ( HCTZ ) in patients with mild-to-moderate hypertension . After a 4- to 5-week single-blind placebo lead-in period , 683 patients with seated diastolic blood pressure ( SeDBP ) between 95 and 110 mm Hg were r and omized to receive once-daily dosing with one of 16 different double-blind , fixed combinations of irbesartan ( 0 , 37.5 , 100 , and 300 mg irbesartan ) and HCTZ ( 0 , 6.25 , 12.5 , and 25 mg HCTZ ) for 8 weeks . The primary efficacy variable was the change from baseline in trough SeDBP after 8 weeks of therapy . Data were analyzed by response surface modeling . At Week 8 , mean changes from baseline in trough SeDBP ( mm Hg ) ranged from -3.5 for placebo , -7.1 to -10.2 for the irbesartan monotherapy groups , -5.1 to -8.3 for the HCTZ monotherapy groups , and -8.1 to -15.0 for the combination groups . Irbesartan plus HCTZ produced additive reductions in both SeDBP and seated systolic BP , with at least one combination producing greater BP reduction than either drug alone ( P < .001 ) . All treatments were well tolerated ; there were no treatment-related serious adverse events . Irbesartan tended to ameliorate the dose-related biochemical abnormalities associated with HCTZ alone . In conclusion , the combination of HCTZ in doses up to 25 mg with irbesartan , in doses up to 300 mg , is safe and produces dose-dependent reductions in BP The aim of this study was to compare the effects of telmisartan/hydrochlorothiazide ( HCTZ ) vs lisinopril/HCTZ combination on ambulatory blood pressure and cognitive function in elderly hypertensive patients . A total of 160 patients , 76 men and 84 women , aged 61–75 years , with sitting diastolic blood pressure ( DBP ) > 90 mmHg and < 110 mmHg and systolic blood pressure ( SBP ) > 140 mmHg were r and omized to receive temisartan 80 mg/HCTZ 12.5 mg o.d . or lisinopril 20 mg/HCTZ 12.5 mg o.d . for 24 weeks , according to a prospect i ve , open-label , blinded end point , parallel-group design . At the end of a 2-week wash-out period and after 12 and 24 weeks of active treatment , 24-h noninvasive ambulatory BP monitoring  ( ABPM ) was performed and cognitive function was evaluated through six different tests ( verbal fluency , Boston naming test , word-list memory , word-list recall , word-list recognition and Trails B ) . Both treatments significantly reduced ambulatory BP .  However , the telmisartan/HCTZ combination produced a greater reduction in 24-h , day-time and night time ABPM values . Lisinopril/HCTZ did not induce significant changes in any of the cognitive function test scores at any time of the study , whereas at both 12 and 24 weeks telmisartan/HCTZ significantly improved the word-list memory score ( + 17.1 and + 15.7 % , respectively , P<0.05 vs baseline ) , the word-list recall score ( + 13.5 and + 16.9 % , P<0.05 ) and the Trails B score ( −33 and −30.5 % , P<0.05 ) . These results suggest that in elderly hypertensive patients  treatment with telmisartan/HCTZ produces a slightly greater reduction in ambulatory BP  than lisinopril/HCTZ combination and , unlike this latter , improves some of the components of cognitive function , particularly episodic memory and visuospatial abilities Lisinopril ( LIS ) is a lysine analog of enalaprilat , the active metabolite of enalapril , an angiotensin-converting enzyme inhibitor ( ACEI ) . Unlike enalapril , the precursor of enalaprilat , LIS is not a prodrug but has equal ACEI efficacy and potency and a slightly longer duration of action after oral administration . Short-term ( 12 weeks ) and long-term ( 24 weeks ) blood pressure control has been studied with LIS , hydrochlorothiazide ( HCTZ ) , and LIS + HCTZ when given once a day . Drug treatment had three phases : ( i ) 2–4 weeks of single-blind placebo washout ; ( ii ) 12 weeks of double-blind comparison therapy with LIS 20 , 40 . and 80 mg vs. HCTZ 12.5 , 25 , and 50 mg , vs. LIS + HCTZ 20 + 12.5 , 40 + 25 . and 80 + 50 mg ; ( iii ) 13–24 weeks single-blind LIS vs. LIS + HCTZ . Starting double-blind therapy at the lowest dose , all three groups doubled the dose at weeks 4 and 8 if BP was not controlled with sitting diastolic BP ( SDBP ) < 90 mm Hg . At the end of 12 weeks of double-blind therapy , uncontrolled HCTZ-only and LIS-only treatment groups were advanced to combination LIS + HCTZ therapy but uncontrolled LIS + HCTZ patients were dropped . Mean BP reductions ( systolic/diastolic , mm Hg ) for all three groups after 12 weeks of double-blind comparison therapy were : ( i ) LIS ( n = 162 ) , – 16.6/-12.5 ; ( ii ) HCTZ ( n = 155 ) , – 10.4/-6.8 : ( iii ) LIS + HCTZ ( n = 74 ) . −23.9/- 18.2 with p < 0.01 for all groups compared to baseline . Significant ( p < 0.01 ) decreases in SDBP with all therapies were seen regardless of race , but nonblack patients responded better than black patients to LIS alone . During the second treatment period ( weeks 13–24 ) , 89 % of patients ( 177/199 ) at week 24 had SDBP ≤ 85 mm Hg or ≥ 10 mm Hg SDBP reduction . By 24 weeks , 82 % ( 72/88 ) of LIS-treated patients maintained this BP control , whereas 84 % ( 48/57 ) of LIS + HCTZ-treated patients and 67 % ( 36/54 ) of HCTZ-treated patients sustained identical BP control . By 22 weeks , 68 % ( 81/119 ) of patients maintained BP control on LIS monotherapy . With ≤ 20 mg LIS therapy , 41 % ( 33/81 ) achieved long-term BP control , whereas 65 % and 72 % of these patients responded to ≤ 40 mg and ≥ 80 mg LIS doses , respectively . Serious adverse clinical effects in all groups were rare ( < s3 % ) during short-term and long-term therapy . In conclusion , LIS therapy alone ( 20–80 mg q.d . ) is more efficacious than HCTZ therapy alone ( 12.5–50 mg q.d . ) . LIS + HCTZ [ ( 20 + 12.5)-(80 + 50 ) mg q.d . ] is more efficacious than either LIS therapy alone ( 20–80 mg q.d . ) or HCTZ therapy alone ( 12.5–50 mg q.d . ) . Lisinopril and LIS + HCTZ  are effective and well tolerated antihypertensive agents in both short- and long-term therapy Objectives Aliskiren is a novel , orally active renin inhibitor . Its antihypertensive efficacy and safety , alone and in combination with hydrochlorothiazide ( HCTZ ) , were investigated in an 8-week , double-blind , placebo-controlled trial in hypertensive patients . The effects of these treatments on plasma renin activity ( PRA ) were also assessed . Methods A total of 2776 patients aged ≥ 18 years with mean sitting diastolic blood pressure ( MSDBP ) 95–109 mmHg were r and omized to receive once-daily treatment with aliskiren ( 75 , 150 or 300 mg ) , HCTZ ( 6.25 , 12.5 or 25 mg ) , the combination of aliskiren and HCTZ , or placebo , in a factorial design . The primary endpoint was the change in MSDBP from baseline to week 8 . PRA was assessed at these timepoints at selected study centers . Results Aliskiren monotherapy was superior to placebo ( P < 0.001 ; overall Dunnett 's test ) in reducing MSDBP and mean sitting systolic blood pressure ( MSSBP ) . Combination treatment was superior to both component monotherapies in reducing BP ( maximum MSSBP/MSDBP reduction of 21.2/14.3 mmHg from baseline with aliskiren/HCTZ 300/25 mg ) , and result ed in more responders ( patients with MSDBP < 90 mmHg and /or ≥ 10 mmHg reduction ) and better control rates ( patients achieving MSSBP/MSDBP < 140/90 mmHg ) than either monotherapy . Aliskiren monotherapy reduced PRA by up to 65 % from baseline . Although HCTZ monotherapy increased PRA by up to 72 % , PRA decreased in all of the combination therapy groups . All active treatments were well tolerated . Conclusions Aliskiren monotherapy demonstrated significant BP lowering , and its effect was considerably greater when combined with HCTZ . Renin inhibition with aliskiren neutralized the compensatory rise in PRA induced by HCTZ Hypertensive patients whose BP was uncontrolled despite the use of antihypertensive agents , including an ARB ( c and esartan 8 mg/day or valsartan 80 mg/day ) , were enrolled . The patients were r and omly assigned to combination therapy with telmisartan 40 mg/day ( changed from current ARB ) and hydrochlorothiazide ( HCTZ ) 12.5 mg/day ( T + H , n = 32 ) or to no change in their current drug regimen ( CTL , n = 32 ) . The observation period was 12 weeks . The office and home BPs were significantly reduced in the T + H compared to those in the CTL . A sufficient and long-acting BP lowering effect , as reflected in decreased early morning BP , was obtained with the combination of low-dose HCTZ and telmisartan without apparent metabolic deterioration During a 12-week , multicenter study to evaluate the efficacy and safety of lisinopril and hydrochlorothiazide ( HCTZ ) for the treatment of obesity-related hypertension , ambulatory blood pressure ( ABP ) monitoring was performed both at baseline and at study completion in 124 patients . Patients were r and omized to three groups : placebo , lisinopril ( 10 , 20 , or 40 mg/day ) , or HCTZ ( 12.5 , 25 , or 50 mg/day ) . All groups were matched with regard to sex , race , age , body mass index , and waist/hip ratio . The primary analysis of ABP data revealed that both lisinopril and HCTZ effectively lowered mean 24-h systolic ( SBP ) and diastolic ( DBP ) blood pressure compared with placebo , ( mean change from baseline SBP/DBP : -12.0/-8.2 , -10.6/-5.5 , and -0.3/-0.5 mm Hg , respectively ) ; however , lisinopril lowered DBP better than HCTZ ( P < .05 ) . Secondary analyses of groups revealed that men responded better to lisinopril than HCTZ ( -11.9/-7.3 v -6.6/-3.5 mm Hg , respectively ) , whereas women responded well to both drugs . White patients responded better to lisinopril than HCTZ , whereas black patients showed a significant response to HCTZ only . Response to treatment was also influenced by patient classification of 24-h blood pressure profiles , ie , " dipper " or " nondipper . " Overall , the majority of obese  hypertensives  were nondippers . Nondippers ( n = 82 ) responded well to both drugs ( -10.4/-6.9 v -12.5/-5.7 mm Hg , P < .05 v placebo ) , whereas dippers ( n = 42 ) responded to lisinopril ( -11.7/ -9.4 mm Hg , P < .05 v placebo and HCTZ ) , but not HCTZ ( -5.6/-4.1 mm Hg , P = NS v placebo ) . Results of 24-h ABP data show that both lisinopril and HCTZ are effective therapies for obesity-related hypertension and that response to treatment is influenced by sex , race , and dipper/nondipper status Background Amlodipine and hydrochlorothiazide ( HCTZ ) are commonly prescribed in Nigeria either as a monotherapy or in combination with other drugs . The present study was design ed to investigate the antihypertensive efficacy of monotherapy with amlodipine or HCTZ and their effects on electrolyte profile in patients with mild to moderate hypertension . Methods A single-blind r and omized clinical study was used ; fifty patients newly diagnosed with mild to moderate hypertension ( aged 33 to 60 years ) were recruited and divided into two groups : amlodipine or hydrochlorothiazide each comprising of 25 subjects . The subjects received 5 mg of amlodipine or 25 mg of hydrochlorothiazide in their respective group once daily for 4 weeks . Blood pressure , serum and urine electrolytes were measured at baseline and weekly throughout the experiment . Results At the end of follow up , amlodipine reduced systolic and diastolic blood pressure significantly more ( p<0.001 ) than HCTZ . At the end of follow up , blood pressure was reduced to normal in 80 % of the subjects in amlodipine group compared to 50 % in HCTZ . Amlodipine had no significant effect on electrolyte profile of subjects unlike HCTZ which significantly changed both their serum and urine electrolytes . Conclusions Monotherapy with amlodipine was more effective than HCTZ in black patients with mild to moderate hypertension and in addition maintained electrolyte balance Antihypertensive efficacy , effects on left ventricular mass index ( LVMI ) and tolerability of telmisartan , an angiotensin II receptor blocker , were compared with those of hydrochlorothiazide ( HCTZ ) .  Adult patients with mild-to-moderate hypertension and an optimal acoustic window by two-dimensional echocardiography were r and omised at baseline to 12 months ' double-blind , once-daily treatment with telmisartan 80 mg or HCTZ 25 mg . Two-dimensional echocardiography and freeh and precordial three-dimensional echocardiography and 24-h ambulatory blood pressure monitoring were performed at baseline and after treatment . Of the 41 telmisartan group patients and 28 HCTZ group patients , 40 and 25 , respectively , completed the study . Following treatment , 24-h mean SBP  ( telmisartan 157 ± 11 vs 133 ± 7 mmHg , P<0.001 ; HCTZ 154 ± 10 vs 144 ± 11 mmHg , P<0.003 ) and DBP  ( telmisartan 96 ± 6 vs 83 ± 5 mmHg , P<0.001 ; HCTZ 95 ± 7 vs 87 ± 8 mmHg , P<0.003 ) were significantly reduced . Telmisartan produced significantly greater 24-h mean SBP and DBP reductions than HCTZ ( P<0.001 ) . LVMI was significantly reduced by telmisartan ( 141 ± 16 vs 125 ± 19 g/m2 , P<0.001 ) , but not by HCTZ ( 139 ± 20 vs 135 ± 22 g/m2 ) . Incidences of adverse events in both the treatment groups were low ; two cases of hypokalaemia  occurred with HCTZ . In conclusion , telmisartan 80 mg was well tolerated and significantly reduced SBP , DBP and LVMI after 12 months ' treatment compared with HCTZ Many patients with hypertension require ≥3 agents to achieve target blood pressure ( BP ) . The efficacy/safety of the dual combinations of valsartan (Val)/hydrochlorothiazide ( HCTZ ) and amlodipine (Aml)/Val in hypertension are well established . This r and omized , double-blind study evaluated the efficacy/safety of triple therapy with Aml/Val/HCTZ for moderate or severe hypertension ( mean sitting systolic BP : ≥145 mm Hg ; mean sitting diastolic BP : ≥100 mm Hg ) . The study included a single-blind , placebo run-in period , followed by double-blind treatment for 8 weeks ; patients were r and omly assigned to 1 of 4 groups titrated to Aml/Val/HCTZ 10/320/25 mg , Val/HCTZ 320/25 mg , Aml/Val 10/320 mg , or Aml/HCTZ 10/25 mg once daily . Dual-therapy recipients received half of the target doses of both agents for the first 2 weeks , titrating to target doses during week 3 . Those on triple therapy received Val/HCTZ 160.0/12.5 mg during week 1 , Aml/Val/HCTZ 5.0/160.0/12.5 mg during week 2 , and target doses of all 3 of the agents during week 3 . Of the 4285 patients enrolled , 2271 were r and omly assigned to treatment , and 2060 completed the study . Triple therapy was significantly superior to all of the dual therapies in reducing mean sitting systolic BP and mean sitting diastolic BP from baseline to end point ( all P<0.0001 ) . Significantly more patients on triple therapy achieved overall BP control ( < 140/90 mm Hg ; P<0.0001 ) and systolic and diastolic control ( P≤0.0002 ) compared with each dual therapy . Aml/Val/HCTZ was well tolerated . The benefits of triple therapy over dual therapy were observed regardless of age , sex , race , ethnicity , or baseline mean sitting systolic BP . In conclusion , this study demonstrates the efficacy/safety of treating moderate and severe hypertension with Aml/Val/HCTZ 10/320/25 mg The study compared valsartan/amlodipine combination with irbesartan/hydrochlorothiazide ( HCTZ ) combination in very elderly hypertensives . After a 4-week placebo period , 94 hypertensives , aged 75 - 89 years were r and omized to valsartan 160mg/amlodipine 5 mg or irbesartan 300mg/HCTZ 12.5 mg for 24 weeks according to a prospect i ve , parallel group study . After 4 weeks amlodipine or HCTZ was doubled in non-responders . Patients were checked every 4 weeks . At each visit clinical sitting , lying and st and ing blood pressure ( BP ) , systolic BP ( SBP ) and diastolic BP ( DBP ) were evaluated , and an electrocardiogram was performed . At the end of the placebo period and of the treatment period a non-invasive  24-h ambulatory BP monitoring  ( ABPM ) was performed and electrolytes and uric acid were evaluated . Both combinations significantly reduced ambulatory BP . In the valsartan/amlodipine group the mean reduction ( -29.9/-15.6 for 24h , -28.6/-14.5mmHg for day-time and -26.2/-17.4mmHg for night-time SBP/DBP ) was similar to that of the irbesartan/HCTZ group ( -29.6/-15.4 for 24h , -29.3/-14.9mmHg for day-time and -25.4/-16.9mmHg for night-time SBP/DBP ) . Both combinations significantly reduced clinical sitting and lying BP values with no difference between treatments . BP changes from lying to st and ing position were significantly greater in the irbesartan/HCTZ group ( -17.2/-9.1mmHg ) than in the valsartan/amlodipine group ( -10.1/-1.9mmHg , p<0.05 for SBP and p<0.01 for DBP vs. irbesartan/HCTZ ) . Potassium significantly decreased and uric acid significantly increased ( -0.4mmol/l , p<0.05 and + 0.5mg/dl , p<0.05 vs. baseline , respectively ) only in the irbesartan/HCTZ group . In conclusion , both combinations were similarly effective in reducing ambulatory and clinical BP in very elderly hypertensives . However , valsartan/amlodipine offered some advantages in terms of less pronounced BP orthostatic changes and absence of metabolic adverse effects In this study we compared the antihypertensive efficacy and tolerability of captopril at 25 mg twice daily , hydrochlorothiazide ( HCTZ ) , 12.5 mg twice daily and placebo in a multicentre , double-blind , r and omized study that included 152 essential hypertensive patients ( 77 males , 75 females , 87 WHO stage I , 65 WHO stage II , aged 69 + /- 4 years , mean + /- s.d . ) .  Supine and st and ing blood pressure were similarly reduced by captopril and HCTZ ( P less than 0.01 for both compared with placebo ) . The heart rate did not change . Captopril ( 25 - 30 mg twice daily ) and HCTZ ( 12.5 mg twice daily ) , alone or in combination , maintained their antihypertensive effect during a 24-week single-blind follow-up study . During the follow-up , diastolic blood pressure remained less than 100 mmHg in seven essential hypertensives on placebo , in 45 on captopril and in 25 on HCTZ .  Side effects were observed in seven essential hypertensives during placebo ( treatment withdrawn in two ) , in eight during HCTZ and in three during captopril .  Serum potassium was reduced ( P less than 0.05 ) and uric acid was increased ( P less than 0.01 ) only during HCTZ . We conclude that captopril and HCTZ have similar antihypertensive efficacy in the elderly ; however , captopril appears to be better tolerated 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 The efficacy and tolerability of losartan 100 mg/hydrochlorothiazide ( HCTZ ) 25 mg and enalapril 10 mg/HCTZ 25 mg were compared in a double-blind , r and omized trial in hypertensive patients inadequately controlled and experiencing side effects on prior therapy . Patients with moderate or severe hypertension , currently treated with at least two single-agent drugs ( excluding angiotensin-converting enzyme inhibitors ) , with a sitting diastolic blood pressure ( DBP ) above 90 mm Hg , and at least one undesirable drug-related symptom were r and omized to once-daily treatment with one of the combinations for 12 weeks .  Losartan/HCTZ lowered sitting DBP from the prior therapy baseline by 13.7 mm Hg and sitting systolic blood pressure 19.3 mm Hg ; similar reductions occurred with enalapril/HCTZ .  Trough sitting DBP was reduced to normal levels ( < 90 mm Hg ) in 63 % of patients switched to the losartan combination and in 58 % of those treated with the enalapril combination . Each combination was associated with improved tolerability compared with prior therapy , although fewer patients reported each of 24 undesirable symptoms after 12 weeks of losartan/HCTZ . The improvement from prior therapy in the occurrence of cough was significantly greater with losartan/HCTZ ( P = .005 ) . Enalapril/HCTZ , but not losartan/HCTZ , increased serum uric acid levels at week 12 . In conclusion , the combination of losartan 100 mg/HCTZ 25 mg offers a beneficial therapeutic option for patients with a history of moderate to severe hypertension whose blood pressure is not adequately controlled or who exhibit side effects while on two or more single-agent antihypertensive drugs . In this population , the switch from prior antihypertensive therapies to once daily losartan 100 mg/HCTZ 25 mg improves blood pressure control and reduces side effects Background Patients with hypertension and cardiovascular disease ( CVD ) , diabetes , or chronic kidney disease ( CKD ) usually require two or more antihypertensive agents to achieve blood pressure ( BP ) goals . Methods The efficacy/safety of olmesartan ( OM ) 40 mg , amlodipine besylate ( AML ) 10 mg , and hydrochlorothiazide ( HCTZ ) 25 mg versus the component dual-combinations ( OM 40/AML 10 mg , OM 40/HCTZ 25 mg , and AML 10/HCTZ 25 mg ) was evaluated in participants with diabetes , CKD , or chronic CVD in the Triple Therapy with Olmesartan Medoxomil , Amlodipine , and Hydrochlorothiazide in Hypertensive Patients Study ( TRINITY ) . The primary efficacy end point was least squares ( LS ) mean reduction from baseline in seated diastolic BP ( SeDBP ) at week 12 . Secondary end points included LS mean reduction in SeSBP and proportion of participants achieving BP goal ( < 130/80 mm Hg ) at week 12 ( double-blind r and omized period ) , and LS mean reduction in SeBP and BP goal achievement at week 52/early termination ( open-label period ) . Results At week 12 , OM 40/AML 10/HCTZ 25 mg result ed in significantly greater SeBP reductions in participants with diabetes ( −37.9/22.0 mm Hg vs −28.0/17.6 mm Hg for OM 40/AML 10 mg , −26.4/14.7 mm Hg for OM 40/HCTZ 25 mg , and −27.6/14.8 mm Hg for AML 10/HCTZ 25 mg ) , CKD ( −44.3/25.5 mm Hg vs −39.5/23.8 mm Hg for OM 40/AML 10 mg , −25.3/17.0 mm Hg for OM 40/HCTZ 25 mg , and −33.4/20.6 mm Hg for AML 10/HCTZ 25 mg ) , and chronic CVD ( −37.8/20.6 mm Hg vs −31.7/18.2 mm Hg for OM 40/AML 10 mg , −30.9/17.1 mm Hg for OM 40/HCTZ 25 mg , and −27.5/16.1 mm Hg for AML 10/HCTZ 25 mg ) ( P<0.05 for all subgroups vs dual-component treatments ) . BP goal achievement was greater for participants receiving triple-combination treatment compared with the dual-combination treatments , and was achieved in 41.1 % , 55.0 % , and 38.9 % of participants with diabetes , CKD , and chronic CVD on OM 40/AML 10/HCTZ 25 mg , respectively . At week 52 , there was sustained BP lowering with the OM/AML/HCTZ regimen . Overall , the triple combination was well tolerated . Conclusions In patients with diabetes , CKD , or chronic CVD , short-term ( 12 weeks ) and long-term treatment with OM 40/AML 10/HCTZ 25 mg was well tolerated , lowered BP more effectively , and enabled more participants to reach BP goal than the corresponding 2-component regimens . Trial Identification Introduction In most treated patients with hypertension , a two or more drug combination is required to achieve adequate blood pressure ( BP ) control . In our study we assessed whether the combination of zofenopril + hydrochlorothiazide ( HCTZ ) was at least as effective as irbesartan + HCTZ in essential hypertensives with at least one additional cardiovascular risk factor , uncontrolled by a previous monotherapy . Methods After a 2-week placebo washout , 361 treated hypertensive patients [ office sitting diastolic BP ( DBP ) , ≥90 mmHg ] , aged 18–75 years , were r and omized double blind to 18-week treatment with zofenopril 30 mg plus HCTZ 12.5 mg or irbesartan 150 mg plus HCTZ 12.5 mg once daily , in an international , multicenter study . After the first 6 and 12 weeks , zofenopril and irbesartan doses could be doubled in non-normalized subjects . The primary study end point was the office sitting DBP reduction after 18 weeks of treatment . Secondary end points included office systolic BP ( SBP ) , ambulatory BP and high sensitivity C-reactive protein ( hs-CRP ) . Results The between-treatment difference for office DBP averaged to + 1.0 ( 95 % CI −0.4 , + 0.8 ) mmHg ( P = 0.150 ) , the upper limit of the 95 % confidence interval being inferior to the protocol -defined non-inferiority limit ( 3 mmHg ) . In the subset of patients with valid ambulatory BP , no difference in 24-h average DBP [ n = 181 ; 6.7 ( 8.7 , 4.6 ) zofenopril + HCTZ vs. 6.3 ( 8.8 , 3.7 ) mmHg irbesartan + HCTZ , P = 0.810 ] and SBP reductions [ 11.7 ( 15.4 , 8.0 ) vs. 12.6 ( 17.2 , 8.0 ) mmHg , P = 0.758 ] were observed between the two treatment groups . hs-CRP was reduced by zofenopril + HCTZ [ −0.52 ( −1.05 , 0.01 ) mg/L ] , while it was increased by irbesartan plus HCTZ [ 0.97 ( 0.29 , 1.65 ) mg/L , P = 0.001 between treatments ] . Conclusion In previously monotherapy-treated , uncontrolled patients with hypertension , zofenopril 30–60 mg + HCTZ 12.5 mg is as effective as irbesartan 150–300 mg plus HCTZ 12.5 mg , with the added value of a potential protective effect against vascular inflammation 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 The Controlled ONset Verapamil INvestigation of Cardiovascular Endpoints ( CONVINCE ) Trial is a r and omized , prospect i ve , double-blind , parallel-group , two-arm , actively controlled , multicenter , international 5-year clinical trial involving 15,000 patients . CONVINCE will compare the incidence of fatal or nonfatal myocardial infa rct ion ( MI ) , fatal or nonfatal stroke , or cardiovascular-disease-related death in two antihypertensive treatment regimens . One treatment arm begins with controlled onset-extended release (COER)-verapamil , which has its major antihypertensive effect 6 - 12 hours after administration . The other arm ( st and ard of care ( SOC ) ) begins with either hydrochlorothiazide ( HCTZ ) or atenolol , one of which is preselected by the investigator for an individual patient prior to r and omization . Secondary objectives include comparisons of the regimens for each of the components of the primary endpoint ( separately ) , death or hospitalization related to cardiovascular disease , efficacy in lowering blood pressure to goal , primary events occurring between 6 am and noon , all-cause mortality , withdrawals from blinded therapy , cancer , and hospitalizations due to bleeding .  Patients may be enrolled if they are hypertensive and at least 55 years of age and have an established second risk factor for cardiovascular disease . Initial medications include COER-verapamil ( 180 mg/d ) , HCTZ ( 12.5 mg/d ) , or atenolol ( 50 mg/d ) . Initial doses are doubled if blood pressure ( BP ) does not reach goal ( systolic BP < 140 mm and diastolic BP < 90 mm Hg ) . If BP is not controlled by the higher dose of the initial medication , HCTZ is added to COER-verapamil , or the SOC choice not initially selected is added in the SOC arm . An ACE-inhibitor is recommended ( although nearly any open-label medication is allowed ) as the third step for patients whose BP is not adequately controlled or who have a contraindication to one of the two SOC medications . Patients take two sets of tablets daily , one in the morning and one in the evening . Although most patients switch from an established antihypertensive medication to r and omized treatment , untreated patients with stages I-III hypertension ( SBP between 140 and 190 or DBP between 90 and 110 mm Hg ) are eligible . Outcomes are monitored by an independent Data and Safety Monitoring Board . Enrollment began during the third quarter of 1996 , and follow-up is to be completed in the third quarter of 2002 The purpose of this trial was to evaluate the antihypertensive efficacy of the concomitant administration of selected doses of hydrochlorothiazide ( HCTZ ) on a background of losartan potassium ( losartan ) 50 mg , a selective angiotensin II receptor antagonist . Patients with essential hypertension ( > or = 95 mmHg inclusion criteria ) with a mean sitting diastolic blood pressure ( SiDBP ) of 105 + /- 0.4 ( S.E. ) mmHg entered a 4-week , single-blind monotherapy period of losartan 50 mg once daily . At the end of the monotherapy period , patients whose blood pressure was adequately controlled were discontinued . Patients whose blood pressure was partially controlled based on a SiDBP > 92 mmHg entered a 12 week double-blind period and were r and omly assigned to either receive placebo ( n = 80 ) , HCTZ 6.25 mg ( n = 80 ) , HCTZ 12.5 mg ( n = 72 ) or HCTZ 25 mg ( n = 80 ) in addition to losartan 50 mg . During the losartan monotherapy period , there was a 4 mmHg fall in SiDBP with a further fall of 5 mmHg after 12 weeks of double-blind therapy in the losartan/placebo control group . Based on the between group differences in BP change from the end of the losartan monotherapy period ( baseline ) to end of 12 weeks of double-blind , the concomitant administration of a very low dose of HCTZ ( 6.25 mg ) with losartan did not significantly decrease SiDBP compared with the fall in blood pressure in the losartan/placebo control group ( diff . between groups = -2 ( 95 % C.I.[-4.1 , + 0.9 ] mmHg ) ) . However , the concomitant administration of HCTZ 12.5 or 25 mg with losartan 50 mg result ed in significantly different ( p < or = 0.05 ) reductions in diastolic blood pressure compared to the losartan/placebo group ( diff . between groups = -4 ( 95 % C.I. [ -6.3 , -1.1 ] mmHg ) for 12.5 mg combination group ; -6 ( 95 % C.I. [ -8.3 , -3.3 ] ) mmHg for the HCTZ 25 mg combination group ) . The proportions of patients treated with losartan plus HCTZ 12.5 mg or 25 mg that achieved a trough SiDBP < 88 mmHg or a trough SiDBP > or = 88 mmHg but with a decrease of at least 5 mmHg were 71 % and 83 % , respectively . The percentage of clinical adverse experiences that were considered drug-related as assessed by the investigator were generally similar across all treatment groups . There were no reports of orthostatic hypotension in any of the treatment groups . Changes in serum glucose , potassium and uric acid were not appreciably different amongst the treatment groups . In summary , in patients with predominantly moderate to severe essential hypertension , the addition of HCTZ 12.5 mg or 25 mg to losartan 50 mg produced effective control of blood pressure in a substantial majority of patients who only partially responded to losartan monotherapy . There were no differences amongst the treatment groups with respect to drug-related adverse experiences in this trial BACKGROUND Recent surveys reveal continuing deficiencies in the awareness , treatment , and control of hypertension . In many cases , failure to achieve blood pressure targets may be attributable to the use of antihypertensive monotherapy . OBJECTIVES This study was undertaken to identify combinations of telmisartan , a new oral angiotensin II type 1-receptor antagonist , and hydrochlorothiazide ( HCTZ ) that might provide greater antihypertensive efficacy than monotherapy with either agent in the treatment of mild to moderate hypertension . It also examined the dose-response surface for the 2 drugs alone and in combination . METHODS This was a multicenter , r and omized , double-blind , placebo-controlled , parallel-group study that employed all cells of a 4 x 5 factorial design . After a 4-week , single-blind , placebo run-in period , men and women between 18 and 80 years of age with mild to moderate hypertension ( defined as mean supine diastolic blood pressure [ DBP ] between 95 and 114 mm Hg during the last 2 weeks of the placebo run-in period and systolic blood pressure [ SBP ] between 114 and 200 mm Hg immediately before r and omization ) were eligible to enter the 8-week , double-blind , double-dummy treatment period . Study comparisons were between once-daily telmisartan monotherapy ( 20 , 40 , 80 , or 160 mg ) , HCTZ monotherapy ( 6.25 , 12.5 , or 25 mg ) , 12 combinations of these telmisartan/HCTZ doses , and placebo . The focus was on 2 combinations : telmisartan 40 mg/HCTZ 12.5 mg and telmisartan 80 mg/HCTZ 12.5 mg . The primary efficacy variable was change in supine trough DBP from baseline to the last evaluable measurement during double-blind treatment . Plasma renin activity and safety parameters , including treatment-emergent adverse events , physical findings , electrocardiograms , and serum electrolyte levels ( which are known to increase with HCTZ treatment ) , were also assessed . RESULTS Of 1293 patients screened , 818 ( 63.3 % ) were enrolled at 47 centers . Of these 818 , 749 ( 91.6 % ) completed the study . The intent-to-treat population ( r and omized with > or = 1 postr and omization blood pressure measurement ) consisted of 807 patients ( 98.7 % ) . Telmisartan 80 mg/HCTZ 12.5 mg significantly decreased mean supine trough SBP/DBP by 23.9/14.9 mm Hg , a benefit of 8.5/3.4 mm Hg compared with telmisartan 80 mg and of 17.0/7.6 mm Hg compared with HCTZ 12.5 mg ( both comparisons , P < 0.01 ) . Telmisartan 40 mg/HCTZ 12.5 mg significantly reduced mean supine SBP by 18.8 mm Hg , a benefit of 6.6 mm Hg compared with telmisartan 40 mg and 11.9 mm Hg compared with HCTZ 12.5 mg ( both , P < 0.01 ) . This same combination significantly reduced mean supine DBP by 12.6 mm Hg , a benefit of 5.3 mm Hg compared with HCTZ 12.5 mg ( P < 0.01 ) , but was not significantly different from telmisartan 40 mg . Telmisartan 80 mg/HCTZ 12.5 mg was significantly more effective than telmisartan 40 mg/HCTZ 12.5 mg in reducing mean supine DBP and SBP ( both , P < 0.05 ) . The response surface and responder analyses confirmed the additive antihypertensive efficacy of the combination of telmisartan and HCTZ . All regimens were well tolerated . CONCLUSIONS Once-daily telmisartan 80 mg/HCTZ 12.5 mg was effective and well tolerated when used to reduce SBP and DBP in patients with mild to moderate hypertension . In addition to enhancing efficacy , this combination protected against potassium depletion , a common side effect of thiazide monotherapy STUDY OBJECTIVES To compare the efficacy of combination therapy with sustained-release diltiazem and hydrochlorothiazide ( DTZ SR-HCTZ ) with that of monotherapy with DTZ SR , HCTZ , or placebo in the treatment of essential hypertension ; and to determine whether the addition of a diuretic to diltiazem at apparent optimum doses of each agent significantly enhances their antihypertensive effects . DESIGN Multicenter , r and omized , double-blind , placebo-controlled , parallel-group trial with a 6-week treatment phase . SETTING Private and university-based clinics . PATIENTS AND PARTICIPANTS Subjects of either sex , ranging in age from 18 - 70 years , with a diagnosis of stable essential hypertension made from two consecutive weekly mean supine diastolic blood pressure ( DBP ) readings of 95 mm Hg or above to 110 mm Hg or less that varied 7 mm Hg or less after 4 - 6 weeks in the baseline phase . Of the patients enrolled , 298 met the inclusion criteria . INTERVENTIONS Combination therapy with DTZ SR-HCTZ 120 mg-12.5 mg , or monotherapy with DTZ SR 120 mg or HCTZ 12.5 mg , or placebo was administered twice daily . MEASUREMENTS AND MAIN RESULTS Combination therapy with DTZ SR-HCTZ lowered both supine DBP and SBP significantly ( p < 0.005 ) more than either single agent . The combination also lowered DBP and SBP significantly more than either monotherapy . During a 12-hour in-clinic monitoring period spanning a dosing interval , both the combination and DTZ SR therapies maintained efficacy , whereas the antihypertensive effects of HCTZ dissipated after 8 hours . Treatment-related adverse events for the combination and HCTZ were similar but slightly greater than those for DTZ SR and placebo . CONCLUSIONS The addition of a diuretic to sustained-release diltiazem produced an enhanced antihypertensive effect compared with monotherapy with either individual agent
The antihypertensive efficacy of HCTZ in its daily dose of 12.5 to 25 mg as measured in head-to-head studies by ambulatory BP measurement is consistently inferior to that of all other drug classes .
Because outcome data at this dose are lacking , HCTZ is an inappropriate first-line drug for the treatment of hypertension
OBJECTIVES The purpose of this study was to evaluate the antihypertensive efficacy of hydrochlorothiazide ( HCTZ ) by ambulatory blood pressure ( BP ) monitoring .
BACKGROUND HCTZ is the most commonly prescribed antihypertensive drug worldwide .
More than 97 % of all HCTZ prescriptions are for 12.5 to 25 mg per day .
The antihypertensive efficacy of HCTZ by ambulatory BP monitoring is less well defined .