title: Gender difference in the response to an angiotensin-converting enzyme inhibitor and a diuretic in hypertensive patients of African descent Comparative Antihypertensive Effects of Hydrochlorothiazide and Chlorthalidone on Ambulatory and Office Blood Pressure Comparison of office, ambulatory, and home blood pressure antihypertensive response to atenolol and hydrochlorthiazide. A comparison of outcomes with angiotensin-converting--enzyme inhibitors and diuretics for hypertension in the elderly. Treatment of ambulatory hypertensives with nebivolol or hydrochlorothiazide alone and in combination. A randomized, double-blind, placebo-controlled, factorial-design trial. Differential effects of angiotensin converting enzyme inhibition and diuretic therapy on reductions in ambulatory blood pressure, left ventricular mass, and vascular hypertrophy. 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 Lisinopril versus hydrochlorothiazide in obese hypertensive patients: a multicenter placebo-controlled trial. Treatment in Obese Patients With Hypertension (TROPHY) Study Group. Comparison of effects of exercise and diuretic on left ventricular geometry, mass, and insulin resistance in older hypertensive adults. [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]. Comparative effects of zofenopril and hydrochlorothiazide on office and ambulatory blood pressures in mild to moderate essential hypertension. Efficacy of different drug classes used to initiate antihypertensive treatment in black subjects: results of a randomized trial in Johannesburg, South Africa. Expedited blood pressure control with initial angiotensin II antagonist/diuretic therapy compared with stepped-care therapy in patients with ambulatory systolic hypertension. Hydrochlorothiazide is superior to isradipine for reduction of left ventricular mass: results of a multicenter trial. The Isradipine Study Group. Mortality after 10 1/2 years for hypertensive participants in the Multiple Risk Factor Intervention Trial. Antihypertensive effect of low-dose hydrochlorothiazide alone or in combination with quinapril in black patients with mild to moderate hypertension. Comparison of atenolol, amlodipine, enalapril, hydrochlorothiazide, and losartan for antihypertensive treatment in patients with obstructive sleep apnea. Lack of agreement between office and ambulatory blood pressure responses to hydrochlorothiazide. Nocturnal reduction of blood pressure and the antihypertensive response to a diuretic or angiotensin converting enzyme inhibitor in obese hypertensive patients. TROPHY Study Group. Utility of semiautomatic clinic and 24-h ambulatory blood pressure measurements to evaluate combination therapy: the Ramipril–Hydrochlorothiazide Hypertension Trial Comparison of indapamide and low-dose hydrochlorothiazide monotherapy in black patients with mild to moderate hypertension. Treatment of hypertension in the elderly with a new calcium channel blocking drug, nitrendipine. Antihypertensive effects of two fixed-dose combinations of losartan and hydrochlorothiazide versus hydrochlorothiazide monotherapy in subjects with ambulatory systolic hypertension. Predictors of antihypertensive drug responses: initial data from a placebo-controlled, randomized, cross-over study with four antihypertensive drugs (The GENRES Study). Candesartan and hydrochlorothiazide in isolated 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. Crossover comparison of atenolol, enalapril, hydrochlorothiazide and isradipine for isolated systolic systemic hypertension. Effects of losartan on hypertension and left ventricular mass: a long-term study Antihypertensive effects of amlodipine and hydrochlorothiazide in elderly patients with ambulatory hypertension. Little effect of ordinary antihypertensive therapy on nocturnal high blood pressure in patients with sleep disordered breathing. Different drug classes have variable effects on blood pressure depending on the time of day. Lacidipine, hydrochlorothiazide and their combination in systolic hypertension in the elderly Laboratory tests as predictors of the antihypertensive effects of amlodipine, bisoprolol, hydrochlorothiazide and losartan in men: results from the randomized, double-blind, crossover GENRES Study Different Effects of Antihypertensive Regimens Based on Fosinopril or Hydrochlorothiazide With or Without Lipid Lowering by Pravastatin on Progression of Asymptomatic Carotid Atherosclerosis: Principal Results of PHYLLIS—A Randomized Double-Blind Trial
abstract: Background The efficacy of angiotensin-converting enzyme ( ACE ) inhibitors in decreasing blood pressure  in African patients is controversial . Objective We examined the ambulatory blood pressure ( ABP ) response to a diuretic and an ACE inhibitor in hypertensive patients of East African descent and evaluated the individual characteristics that determined treatment efficacy . Design A single-blind r and omized AB/BA crossover design . Setting Hypertensive families of East African descent from the general population in the Seychelles . Participants Fifty-two ( 29 men and 23 women ) out of 62 eligible hypertensive patients were included . Main outcome measures ABP response to 20 mg lisinopril ( LIS ) daily and 25 mg hydrochlorothiazide ( HCT ) daily given for a 4-week period . Results The daytime systolic/diastolic ABP response to HCT was 4.9 [ 95 % confidence interval ( CI ) 1.2–8.6]/3.6 ( 1.0–6.2 ) mmHg for men and 12.9 (9.2–16.6)/6.3 ( 3.7–8.8 ) mmHg for women . With LIS the response was 18.8 (15.0–22.5)/14.6 ( 12.0–17.1 ) mmHg for men and 12.4 (8.7–16.2)/7.7 ( 5.1–10.2 ) mmHg for women . The night-time systolic/diastolic response to HCT was 5.0 (0.6–9.4)/2.7 [ (−0.4)–5.7 ] mmHg for men and 11.5 (7.1–16.0)/5.7 ( 2.6–8.8 ) mmHg for women , and to LIS was 18.7 (14.2–22.1)/15.4 ( 12.4–18.5 ) mmHg for men and 3.5 [(−1.0)–7.9]/2.3 [ (−0.8)–5.4 ] mmHg for women . Linear regression analyses showed that gender is an independent predictor of the ABP responses to HCT and to LIS . Conclusions Hypertensive patients of African descent responded better to  LIS  than to HCT .  Men responded better to LIS than to HCT and women responded similarly to both drugs Low-dose thiazide-type diuretics are recommended as initial therapy for most hypertensive patients .  Chlorthalidone has significantly reduced stroke and cardiovascular end points in several l and mark trials ; however , hydrochlorothiazide remains favored in practice . Most clinicians assume that the drugs are interchangeable , but their antihypertensive effects at lower doses have not been directly compared . We conducted a r and omized , single-blinded , 8-week active treatment , crossover study comparing chlorthalidone 12.5 mg/day ( force-titrated to 25 mg/day ) and hydrochlorothiazide 25 mg/day ( force-titrated to 50 mg/day ) in untreated hypertensive patients . The main outcome , 24-hour ambulatory blood pressure ( BP ) monitoring , was assessed at baseline and week 8 , along with st and ard office BP readings every 2 weeks . Thirty patients completed the first active treatment period , whereas 24 patients completed both . An order – drug – time interaction was observed with chlorthalidone ; therefore , data from only the first active treatment period was considered . Week 8 ambulatory BPs indicated a greater reduction from baseline in systolic BP  with chlorthalidone 25 mg/day compared with hydrochlorothiazide 50 mg/day ( 24-hour mean = −12.4±1.8 mm Hg versus −7.4±1.7 mm Hg ; P=0.054 ; nighttime mean = −13.5±1.9 mm Hg versus −6.4±1.8 mm Hg ; P=0.009 ) . Office systolic BP reduction was lower at week 2 for chlorthalidone 12.5 mg/day versus hydrochlorothiazide 25 mg/day ( −15.7±2.2 mm Hg versus −4.5±2.1 mm Hg ; P=0.001 ) ; however , by week 8 , reductions were statistically similar ( −17.1±3.7 versus −10.8±3.5 ; P=0.84 ) . Within recommended doses , chlorthalidone is more effective in lowering systolic BPs  than hydrochlorothiazide , as evidence d by 24-hour ambulatory BPs . These differences were not apparent with office BP measurements 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 BACKGROUND Treatment of hypertension with diuretics , beta-blockers , or both leads to improved outcomes . It has been postulated that agents that inhibit the renin-angiotensin system confer benefit beyond the reduction of blood pressure alone . We compared the outcomes in older subjects with hypertension who were treated with angiotensin-converting-enzyme ( ACE ) inhibitors with the outcomes in those treated with diuretic agents . METHODS We conducted a prospect i ve , r and omized , open-label study with blinded assessment of end points in 6083 subjects with hypertension who were 65 to 84 years of age and received health care at 1594 family practice s. Subjects were followed for a median of 4.1 years , and the total numbers of cardiovascular events in the two treatment groups were compared with the use of multivariate proportional-hazards models . RESULTS At base line , the treatment groups were well matched in terms of age , sex , and blood pressure . By the end of the study , blood pressure had decreased to a similar extent in both groups ( a decrease of 26/12 mm Hg ) . There were 695 cardiovascular events or deaths from any cause in the ACE-inhibitor group ( 56.1 per 1000 patient-years ) and 736 cardiovascular events or deaths from any cause in the diuretic group ( 59.8 per 1000 patient-years ; the hazard ratio for a cardiovascular event or death with ACE-inhibitor treatment was 0.89 [ 95 percent confidence interval , 0.79 to 1.00 ] ; P=0.05 ) . Among male subjects , the hazard ratio was 0.83 ( 95 percent confidence interval , 0.71 to 0.97 ; P=0.02 ) ; among female subjects , the hazard ratio was 1.00 ( 95 percent confidence interval , 0.83 to 1.21 ; P=0.98 ) ; the P value for the interaction between sex and treatment-group assignment was 0.15 . The rates of nonfatal cardiovascular events and myocardial infa rct ions decreased with ACE-inhibitor treatment , whereas a similar number of strokes occurred in each group ( although there were more fatal strokes in the ACE-inhibitor group ) . CONCLUSIONS Initiation of antihypertensive treatment involving ACE inhibitors in older subjects , particularly men , appears to lead to better outcomes than treatment with diuretic agents , despite similar reductions of blood pressure This placebo-controlled multifactorial design trial assessed the antihypertensive efficacy of nebivolol , a novel cardioselective beta 1-blocker with vasodilating properties , and hydrochlorothiazide monotherapy and in combination . After a 4-week placebo period , 240 white patients with a mean daytime ambulatory blood pressure of > or = 90 mm Hg were r and omized to receive either placebo , nebivolol ( 1 , 5 , or 10 mg ) , hydrochlorothiazide ( 12.5 or 25 mg ) , or one of the six possible combinations of nebivolol and hydrochlorothiazide for 12 weeks . A dose-related reduction in clinic and ambulatory blood pressure was demonstrated for each drug as monotherapy and for the two drugs in combination . Nebivolol , 5- and 10-mg doses , showed a larger effect than hydrochlorothiazide doses on clinic blood pressure and over the 24-h interval . Moreover , the combination doses had substantial antihypertensive effects that were sustained over the entire 24-h profile with a greater effect observed with the higher dose combinations . The reduction in ambulatory blood pressure was further substantiated by the reduction of blood pressure loads ( % of BP > 140/90 mm Hg awake and > 120/80 mm Hg asleep ) to as low as 11.5 % with 10 mg of nebivolol combined with 25 mg of hydrochlorothiazide . Nebivolol and hydrochlorothiazide were well tolerated . We provided evidence that nebivolol , given as monotherapy or in combination with low dose of hydrochlorothiazide , is effective in reducing clinic and 24-h ambulatory blood pressure in patients with ambulatory hypertension . The results provided further evidence for the use of ambulatory blood pressure monitoring and factorial design s when investigating new antihypertensive agents Diuretic-based therapy is less effective in reducing the cardiac complications of hypertension than the risk of stroke and may be less effective in reducing left ventricular ( LV ) mass than is therapy with angiotensin converting enzyme ( ACE ) inhibition . In view of the strong association of LV hypertrophy with cardiovascular risk , this study was design ed to compare the impact of therapy with a diuretic and ACE inhibition on cardiac and vascular structure . Fifty essential hypertensives ( 74 % male , 88 % nonwhite ) participated in a double-blind study for 6 months and were r and omized to either ramipril or hydrochlorothiazide ( HCTZ ) . Echocardiography , carotid ultrasonography  , and  ambulatory blood pressure ( BP ) monitoring were performed at baseline and 3 and 6 months after initiation of therapy . The 22 ramipril patients were comparable to the 28 HCTZ patients at baseline in age , race , and 24-h BP . Although HCTZ result ed in a greater reduction in 24-h BP , only treatment with ramipril result ed in a decrease in LV mass ( 193 to 179 g , P < .005 , v 184 to 182 g , P = NS ) , attributable to a reduction in wall thicknesses but not in chamber diameter . In multivariate analysis , both change in BP and treatment group were independent predictors of change in LV mass . Importantly , although neither drug reduced carotid artery cross-sectional area , relative wall thickness increased due to a tendency for vessel diameter to decrease and wall thickness to increase , particularly in the diuretic group . Ramipril caused a sustained fall in plasma angiotensin II , whereas HCTZ increased angiotensin II levels . Although diuretic therapy was more effective in lowering ambulatory BP in this predominantly nonwhite population , only therapy with ACE inhibition was associated with regression of LV mass . Vascular geometry was altered consistent with the reduction in distending pressure result ing in vascular remodelling 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 Because obesity-associated hypertension has unique hemodynamic and hormonal profiles , certain classes of antihypertensive agents may be more effective than others as monotherapy . Thus , we compared the efficacy and safety of the angiotensin-converting enzyme inhibitor lisinopril and the diuretic hydrochlorothiazide in a 12-week , multicenter , double-blind trial in 232 obese patients with hypertension . Patients with an office diastolic pressure between 90 and 109 mm Hg were r and omized to treatment with daily doses of lisinopril ( 10 , 20 , or 40 mg ) ,  hydrochlorothiazide  ( 12.5 , 25 , or 50 mg ) , or  placebo . Mean body mass indexes were similar for all patients . At week 12 , lisinopril and hydrochlorothiazide effectively lowered office diastolic ( -8.3 and -7.7 versus -3.3 mm Hg , respectively ; P<.005 ) and systolic ( -9.2 and -10.0 versus -4.6 mm Hg , respectively ; P<.05 ) pressures compared with placebo .  Ambulatory blood pressure monitoring confirmed that lisinopril and hydrochlorothiazide effectively lowered 24-hour blood pressure compared with placebo ( P<.001 ) . Significant dose-response differences were observed between treatments . Sixty percent of patients treated with lisinopril had an office diastolic pressure < 90 mm Hg compared with 43 % of patients treated with hydrochlorothiazide ( P<.05 ) . Responses to therapies differed with both race and age . Neither treatment significantly affected insulin or lipid profiles ; however , plasma glucose increased significantly after 12 weeks of hydrochlorothiazide therapy compared with lisinopril ( + 0.31 versus -0.21 mmol/L ; P<.001 ) . Hydrochlorothiazide also decreased serum potassium levels by 0.4 mmol/L from baseline . In conclusion , lisinopril was as effective as hydrochlorothiazide in treating obese patients with hypertension . Treatment with angiotensin-converting enzyme inhibitors may show greater efficacy as monotherapy at lower doses compared with thiazide diuretics , may have a more rapid rate of response , and may offer advantages in patients at high risk of metabolic disorders To compare the effects of exercise training and hydrochlorothiazide on left ventricular ( LV ) geometry and mass , blood pressure ( BP ) , and hyperinsulinemia in older hypertensive adults , we studied 28 patients r and omized either to a group ( age 66.4 + /- 1.3 yr ; n = 16 ) that exercised or to a group ( age 65.3 + /- 1.2 yr ; n = 12 ) that received hydrochlorothiazide for 6 mo .  Endurance exercise training induced a 15 % increase in peak aerobic power . The reduction in systolic BP was twofold greater with thiazide than with exercise ( 26.6 + /- 12.2 vs. 11.5 + /- 10.9 mmHg ) . Exercise and thiazide reduced LV wall thickness , LV mass index ( 14 % in each group ) , and the LV wall thickness-to-radius ratio ( h/r ) similarly ( exercise : before 0.48 + /- 0.2 , after 0.42 + /- 0.01 ; thiazide : before 0.47 + /- 0.04 , after 0.40 + /- 0.04 ; P = 0.017 ) . The reductions in systolic BP and h/r were correlated in the exercise group ( r = 0.70 , P = 0.005 ) but not in the thiazide group . Exercise training reduced glucose-stimulated hyperinsulinemia ( before : 13.65 + /- 2.6 vs. 9.84 + /- 1.5 mU.ml(-1).min ; P = 0.04 ) and insulin resistance . Thiazide did not affect plasma insulin levels . The results suggest that although exercise is less effective in reducing systolic BP than thiazide , it can induce regression of LV hypertrophy similar in magnitude to thiazide . Unlike hydrochlorothiazide , exercise training can improve insulin resistance and aerobic capacity in older hypertensive people 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 1 . Thirty-eight patients with mild to moderate essential hypertension ( seated diastolic 95 - 110 mm Hg ) were r and omized double-blind to treatment with either zofenopril ( n = 19 ) or hydrochlorothiazide ( n = 19 ) over a period of 12 weeks . 2 . Office blood pressure , heart rate , side effects and metabolic changes were assessed at the end of the run-in period on placebo and after 4 , 8 , 12 weeks treatment at the same time , 22 - 24 h after the last dosing . Ambulatory recordings over 14 h ( 8 h to 22 h ) were performed at the end of placebo period and after active treatment for 12 weeks . 3 . The two regimes reduced office blood pressures equally with minimal additional effect seen on increasing the dose . Both zofenopril and hydrochlorothiazide lowered average baseline ambulatory blood pressure , but zofenopril had greater efficacy in reducing BP during some working hours . 4 . Adverse reactions were mild and transient with both drugs . There were no significant changes in laboratory values . 5 . Thus hydrochlorothiazide and zofenopril given once daily at low dosage both reduce office and ambulatory blood pressures and are well tolerated BACKGROUND Thiazides are recommended to initiate antihypertensive drug treatment in black subjects . OBJECTIVE To test the efficacy of this recommendation in a South African black cohort . METHODS Men and women ( N = 409 ) , aged 18 to 70 years , with a mean ambulatory daytime diastolic blood pressure between 90 and 114 mm Hg , were r and omized to 13 months of open-label treatment starting with the nifedipine gastrointestinal therapeutic system ( 30 mg/d , n = 233 ) , sustained-release verapamil hydrochloride ( 240 mg/d , n = 58 ) , hydrochlorothiazide ( 12.5 mg/d , n = 58 ) , or enalapril maleate ( 10 mg/d , n = 60 ) . If the target of reducing daytime diastolic blood pressure below 90 mm Hg was not attained , the first-line drugs were titrated up and after 2 months other medications were added to the regimen . RESULTS While receiving monotherapy ( 2 months , n = 366 ) , the patients ' systolic and diastolic decreases in daytime blood pressure averaged 22/14 mm Hg for nifedipine , 17/11 mm Hg for verapamil , 12/8 mm Hg for hydrochlorothiazide , and 5/3 mm Hg for enalapril . At 2 months the blood pressure of more patients treated with nifedipine was controlled : 133 ( 63.3 % , P</=.03 ) vs 20 ( 39.9 % ) receiving verapamil , 21 ( 40.4 % ) receiving hydrochlorothiazide , and 11 ( 20.8 % ) receiving enalapril . At 13 months ( n = 257 ) , more patients ( P<.001 ) continued receiving monotherapy with nifedipine ( 94/154 [ 61.0 % ] ) or verapamil ( 22/35 [ 62.9 % ] ) than hydrochlorothiazide ( 10/39 [ 25.6 % ] ) or enalapril ( 1/29 [ 3.4 % ] ) . A sustained decrease of left ventricular mass ( P<.001 ) with no between-group differences was achieved at 4 and 13 months . CONCLUSIONS In contrast to current recommendations , calcium channel blockers are more effective than thiazides as initial treatment in black subjects with hypertension . If treatment is started with thiazides or converting-enzyme inhibitors , combination therapy is more likely to be required to control blood pressure and reduce left ventricular mass 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 OBJECTIVES We sought to determine the efficacy of isradipine in reducing left ventricular ( LV ) mass and wall thickness in hypertensive patients . BACKGROUND LV hypertrophy on the echocardiogram is a strong predictor of cardiovascular events . Reduction of LV mass may be a desirable goal of drug therapy for hypertension . However , although thiazide diuretic drugs have been advocated as first-line therapy for hypertension , their efficacy in reducing LV mass has been question ed . METHODS Patients with mild to moderate diastolic hypertension and LV mass in excess of 1 SD of normal values were r and omized to isradipine ( n = 89 ) or hydrochlorothiazide therapy ( n = 45 ) . Evaluations were obtained at baseline , after 3 and 6 months of treatment and 2 weeks after treatment was stopped . RESULTS At 6 months , LV mass decreased by 43 + /- 45 g ( mean + /- SD ) with hydrochlorothiazide ( p < 0.001 ) but only by 11 + /- 48 g with isradipine ( p = NS ; between-group comparison , p < 0.001 ) . Two weeks after drug therapy was stopped , LV mass remained 24 + /- 41 g lower than that at baseline in the hydrochlorothiazide group ( p = 0.003 ) but only 7 + /- 50 g lower in the isradipine group ( p = NS ) . Septal and posterior wall thicknesses were significantly and equally reduced with both isradipine and hydrochlorothiazide . Greater LV mass reduction with hydrochlorothiazide was related to a 2.8 + /- 3.3-mm reduction of LV cavity size with hydrochlorothiazide but no reduction with isradipine . At 6 months of treatment , diastolic blood pressure ( BP ) by design was equally reduced in both treatment groups . At 3 months , systolic BP was reduced by 17 + /- 15 mm Hg with isradipine and by 26 + /- 15 and 25 + /- 17 mm Hg at 3 and 6 months , respectively , with hydrochlorothiazide ( p = 0.003 , between-group comparison ) . However , on stepwise multivariable regression analysis , treatment selection ( partial r2 = 0.082 , p = 0.001 ) , change in average 24-h systolic BP ( partial r2 = 0.032 , p = 0.029 ) and change in average sitting systolic BP ( partial r2 = 0.017 , p = 0.096 ) were predictive of LV mass reduction . CONCLUSIONS Despite an equivalent reduction of diastolic BP , 6 months of therapy with hydrochlorothiazide is associated with a substantial reduction of LV mass , greater than that with isradipine . The superior efficacy of hydrochlorothiazide for LV mass reduction is associated with a greater reduction of systolic BP as well as drug selection itself . These data may have important therapeutic implication The Multiple Risk Factor Intervention Trial ( MRFIT ) is a r and omized primary prevention trial that tested the effect of a multifactor intervention program on coronary heart disease ( CHD ) mortality in 12,866 high-risk men aged 35 - 57 years . Men were r and omly assigned to either a special intervention ( SI ) program , which consisted of dietary advice for lowering blood cholesterol levels , counseling aim ed at cessation for cigarette smokers , and stepped-care treatment for hypertension for those with elevated blood pressure , or to their usual sources of health care within the community ( UC ) . Among the 12,866 r and omized men , 8,012 ( 62 % ) were hypertensive at baseline . For this subgroup , mortality rates with 10.5 years of follow-up were lower for the SI than for the UC group by 15 % ( p = 0.19 ) for CHD and 11 % ( p = 0.13 ) for all causes . These results reflected more favorable outcomes for SI compared with UC hypertensive men during the 3.8 posttrial years ( March 1982 through December 1985 ) than during the preceding 6 - 8 years ( through February 1982 ) . During the posttrial years , death rates were lower for SI than for UC men by 26 % ( p = 0.09 ) for CHD and 23 % ( p = 0.02 ) for all causes . For those with diastolic blood pressure equal to or more than 100 mm Hg , this posttrial trend was a continuation of a trend during the trial ; therefore , with 10.5 years of follow-up , death rates were markedly lower for SI than for UC by 36 % ( p = 0.07 ) for CHD and 50 % ( p = 0.0001 ) for all causes . Similarly , for those without baseline resting electrocardiographic abnormalities , the favorable posttrial outcome for the SI group was a continuation of a trend during the trial . In contrast , for those with baseline diastolic blood pressure of 90 - 99 mm Hg and for those with baseline resting electrocardiographic abnormalities , the favorable posttrial mortality findings for the SI group were a reversal of unfavorable trends recorded during the trial . Two factors appear to have contributed to this more favorable mortality trend for the SI group : 1 ) a change in the diuretic treatment protocol for SI men about 5 years after r and omization , which involved replacement of hydrochlorothiazide with chlorthalidone at a daily maximum dose of 50 mg ; and 2 ) a favorable effect of intervention on nonfatal cardiovascular events during the trial years . In addition , delay until the full impact of beneficial effects on mortality end points from smoking cessation and cholesterol lowering could have contributed . ( ABSTRACT TRUNCATED AT 400 WORDS 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 We compared the effects of atenolol ( 50 mg ) , amlodipine ( 5 mg ) , enalapril ( 20 mg ) , hydrochlorothiazide ( 25 mg ) , and losartan ( 50 mg ) given in once-daily oral doses on office and ambulatory blood pressures ( BPs ) in patients with hypertension and obstructive sleep apnea ( OSA ) . Each of 40 r and omized patients was treated in sequence with two of the five agents ( balanced incomplete block design ) . Treatment periods lasted 6 wk and were separated by a 3-wk washout period . Changes in BP from baseline with the study substances were compared through analysis of variance . Office diastolic BP , our primary outcome variable , was most effectively lowered by atenolol , with all four post hoc differences between atenolol and the remaining substances being statistically significant . Reductions in office systolic and daytime ambulatory BP were not significantly different among the five compounds . However , atenolol reduced mean nighttime ambulatory diastolic and systolic BP more effectively than did amlodipine , enalapril , or losartan ( but not hydrochlorothiazide ) . Severity of sleep-disordered breathing and well-being during the day were not significantly influenced by any of the study compounds . Our findings are in accordance with the hypothesis that an overactivity of the sympathetic nervous system is an important mechanism behind the development or maintenance of hypertension in patients with OSA BACKGROUND Differences between the antihypertensive responses to drug therapy measured by office blood pressure ( OBP ) and ambulatory blood pressure monitoring ( ABPM ) techniques have been noted but rarely analyzed . We studied whether the OBP and 24-h ABPM responses to hydrochlorothiazide differ and , if so , the relevance of these differences . METHODS The  OBP and ABPM responses to hydrochlorothiazide ( 25 mg/d , for 4 weeks ) were measured in 228 subjects with essential hypertension , and mean responses were compared between methods using the Student paired t test . To assess variation in the agreement between OBP and ABPM responses among subjects , the limits of agreement were calculated as the mean difference between OBP and ABPM responses + /-2 st and ard deviations . RESULTS The mean systolic OBP response was 4.8 mm Hg greater than the response measured by ABPM ( -14.3 v -9.5 mm Hg , P < .001 ) , and the mean diastolic OBP response was 2.1 mm Hg greater than the response measured by ABPM ( -7.5 v -5.5 , P < .001 ) . The limits of agreement between the OBP and ABPM responses ranged from -18.7 to + 28.2 mm Hg for systolic response and from -12.9 to + 17.1 mm Hg for diastolic response . The systolic and diastolic OBP and ABPM responses were in opposite directions in 22.8 % and 23.7 % of the subjects , respectively . CONCLUSIONS Compared to ABPM , OBP overestimates the mean systolic and mean diastolic blood pressure responses to hydrochlorothiazide . Variation among subjects in the magnitude and direction of responses renders OBP an unreliable predictor of ABPM responses 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 Angiotensin-converting enzyme inhibitors combined with higher doses of hydrochlorothiazide ( HCT ) , that is , 25 mg daily , have been recognized as an effective form of antihypertensive therapy . To evaluate the coadministration of 20 mg ramipril with 25 mg HCT , we carried out a r and omized , double-blind , controlled trial with two dose schedules of ramipril ( 20 mg q.d . and 10 mg b.i.d . ) and HCT monotherapy arms as comparators in 354 patients with stage 2 hypertension .  The clinic blood pressure ( BP ) was assessed using a semiautomatic digital device and  24-h BP  was measured using ambulatory BP recordings at baseline and after 8 weeks of therapy . At baseline , the demographics and baseline BP values were similar in the four treatment groups ( age : 51–53 years , 52–58 % male , 64–68 % non-black , clinic BP : 155–158/103–104 mm Hg ) . Ramipril – HCT induced significantly greater reductions in both the clinic and ambulatory BP than the HCT and ramipril monotherapy treatments ( for example , additional reductions in ambulatory BP on ramipril-HCT ranged from −7.3/−5.2 to −10.3/−7.4 mm Hg compared to the monotherapies , all P<0.001 ) . Reductions from baseline were still numerically greater for the clinic BPs derived from device measurements than those for the BP values derived from 24-h ambulatory BP measurements ( changes in clinic diastolic BP ranged from −8.5 to −15.5 mm Hg across treatment groups , whereas changes in ambulatory diastolic BP were −4.7 to −12.0 mm Hg for the same groups ) . Thus , these data support the use of ambulatory BP monitoring even when automated BP devices are used for the assessment of clinical BP in trials that attempt to differentiate BP responses among active comparator groups . In conclusion , based on its efficacy and tolerability profile the combination of ramipril and HCT was shown to be effective therapy for the treatment of stage 2 hypertension OBJECTIVES To assess , using ambulatory blood pressure monitoring ( ABPM ) , the antihypertensive efficacy of hydrochlorothiazide 12.5 mg and indapamide 2.5 mg given as a monotherapy over 3 months to black patients with mild to moderate essential hypertension . DESIGN Single-centre , prospect i ve , r and omised open pilot study in three phases : ( i ) 1-week drug-free washout period ; ( ii ) 2-week placebo run-in phase ; and ( iii ) 3-month prospect i ve open-label active treatment period . RESULTS Forty-two black patients with mean daytime diastolic BP ( DBP ) > or = 90 mmHg and < or = 115 mmHg ( mean age 57 + /- 11 years , 28 women/14 men ) were enrolled into the study . Overall , a profound and sustained BP reduction was achieved with indapamide at 3 months ( N = 20 ) . The 24-hour BP decreased from 150 + /- 17/94 + /- 6 mmHg to 130 + /- 19/82 + /- 9 mmHg ( P < 0.0001 for systolic BP ( SBP ) and DBP at 3 months versus baseline ) ; the mean daytime BP decreased from 155 + /- 15/98 + /- 6 mmHg to 134 + /- 18/87 + /- 10 mmHg ( P < 0.0001 for SBP and DBP at 3 months versus baseline ) . The overall control ( mean daytime DBP < 90 mmHg ) and response ( decrease in daytime DBP > or = 10 mmHg ) rates achieved with indapamide were 10/20 ( 50 % ) and 13/20 ( 65 % ) , respectively . In contrast , monotherapy with hydrochlorothiazide result ed in more modest BP reduction and control and response rates at 3 months ( N = 22 ) . The 24-hour BP decreased from 147 + /- 14/94 + /- 7 mmHg to 139 + /- 19/88 + /- 2 mmHg ( P < 0.05 for DBP at 3 months versus baseline , P = NS for SBP ) ; the mean daytime BP decreased from 151 + /- 14/98 + /- 5 mmHg to 144 + /- 16/93 + /- 10 mmHg ( P < 0.05 for DBP at 3 months versus baseline , P = NS for SBP ) . The corresponding control and response rates were 7/22 ( 32 % ) and 8/22 ( 36 % ) . Both hydrocholorothiazide and indapamide caused significant hypokalaemia . CONCLUSIONS Monotherapy with indapamide is associated with greater BP reduction and control and response rates than monotherapy with low-dose hydrochlorothiazide and may be an appropriate choice of antihypertensive diuretic therapy in black South African patients with mild to moderate hypertension PURPOSE Treatment of hypertension in the elderly decreases cardiovascular morbidity and mortality . We hypothesized that nitrendipine would be efficacious in the treatment of hypertension in the elderly . We evaluated potential differences between nitrendipine and the commonly used drug hydrochlorothiazide ( HCTZ ) . PATIENTS AND METHODS The study was conducted as a double-blind r and omized clinical trial of nitrendipine or HCTZ .  Thirty hypertensive subjects over age 60 with a median sitting blood pressure greater than or equal to 95 mm of Hg were recruited into the study . A diastolic blood pressure with treatment of less than 95 mm Hg with a 5 mm Hg or greater decrease from baseline was considered a successful response . RESULTS Nitrendipine decreased mean ( + /- SEM ) blood pressure from 163 + /- 3/102 + /- 1 to 142 + /- 2/89 + /- 2 mm Hg , and HCTZ decreased it from 164 + /- 4/102 + /- 1 to 143 + /- 5/91 + /- 2 mm Hg . A greater proportion of patients had a successful response with nitrendipine ( 81 percent ) than with HCTZ ( 64 percent ) . The antihypertensive effect of nitrendipine twice daily appeared to be sustained for 24 hours . Blood pressure response to exercise was attenuated with both drugs . HCTZ caused gout , leg pains , muscle aches , hypokalemia , increased uric acid levels , and increased total cholesterol and triglyceride levels .  Nitrendipine caused edema and tachycardia . CONCLUSION Nitrendipine significantly reduces blood pressure with few side effects and no adverse metabolic effects , and offers a reasonable alternative for treating hypertension in the elderly 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 BACKGROUND Only a minority of hypertensive individuals is adequately controlled for their hypertension , partially because reliable predictors for efficient antihypertensive drug therapy are lacking . METHODS In a prospect i ve , r and omized , double-blind , cross-over , placebo-controlled study ( The GENRES Study ) , 208 moderately hypertensive Finnish men ( aged 35 to 60 years ) were treated for 4 weeks with antihypertensive drugs from four different classes : amlodipine ( 5 mg ) , bisoprolol ( 5 mg ) , hydrochlorothiazide ( 25 mg ) , or losartan ( 50 mg ) daily . Each individual received each of the four monotherapies in a r and omized order . Four-week placebo periods were included before and between drug treatment periods . Antihypertensive responses were assessed with 24-h ambulatory and office measurements and analyzed according to age , body mass index , triceps skin fold thickness , waist-to-hip ratio , duration of hypertension , number of previous antihypertensive drugs , number of affected parents , and blood pressure ( BP ) levels , and profiles during placebo periods . RESULTS The median BP responses in 24-h ambulatory recordings ( systolic/diastolic ) were 11/8 mm Hg for bisoprolol , 9/6 mm Hg for losartan , 7/5 mm Hg for amlodipine , and 5/2 mm Hg for hydrochlorothiazide . The highest pairwise within-subject correlations in BP responses were seen for the combinations of bisoprolol-losartan and amlodipine-hydrochlorothiazide . The BP responses to bisoprolol and losartan did not vary according to the variables .  Amlodipine and hydrochlorothiazide responses were positively correlated with age , placebo BP level , and lower night-time dipping on placebo . CONCLUSIONS Baseline clinical and BP parameters may be used to predict the efficacy of antihypertensive therapies . The GENRES Study material should provide an excellent platform for future pharmacogenetic analyses of antihypertensive drug responsiveness Aim : We investigated the efficacy and safety of daily c and esartan 8/16 mg and hydrochlorothiazide 12.5 mg as monotherapy and in combination in older patients with systolic hypertension . Methods : The study used a double-blind r and omized placebo-controlled crossover design . Treatment phases were of 6 weeks duration . For inclusion , patients were aged 55 - 84 years with sitting systolic blood pressure ( SBP ) 160 - 210 mmHg and diastolic blood pressure ( DBP ) < 95 mmHg . Nineteen patients ( 11 male , eight female , median age 68 years ) completed the study . Major findings : Compared with the placebo phase , clinic and ambulatory SBP was significantly reduced with both dose-adjusted c and esartan and fixed-dose hydrochlorothiazide as monotherapy , the effect of c and esartan being greater than that of hydrochlorothiazide . In combination , the effects of the two drugs were additive . Both drugs were well tolerated either as monotherapy or in combination . Conclusion : Both c and esartan and a low dose of hydrochlorothiazide are effective and well-tolerated antihypertensive agents in isolated systolic hypertension with additive effects in combination . C and esartan was more effective than hydrochlorothiazide , although it is possible that dose adjustment only of c and esartan could have enhanced its relative effectiveness 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 The benefit of antihypertensive therapy in reducing cardiovascular morbidity and mortality associated with isolated systolic hypertension has now been established by the Systolic Hypertension in the Elderly Program . However , there is little information about the relative effectiveness of different drug regimens in this condition . This study compared the efficacy and tolerability of 50 mg of atenolol , 10 mg of enalapril , 25 mg of hydrochlorothiazide and 2.5 mg of isradipine in the treatment of isolated systolic hypertension . After a 3-week placebo run-in phase , 24 subjects were r and omized into a 4-period double-blind crossover study by use of an orthogonal latin square design . Treatment periods were of 6 weeks ' duration with titration to a higher dose after 4 weeks in those not reaching goal blood pressure ( BP ) . Each active treatment was followed by a 3-week placebo washout . Casual clinic and 24-hour ambulatory BP ( Accutracker II ) were measured at the end of each treatment phase . Routine biochemistry was also performed after the placebo run-in , at the end of each active treatment phase , and after the placebo run-out . Of the 24 subjects entered ( mean age 72.3 years , 38 % men ) 20 completed the whole study .  Mean + /- st and ard deviation of supine clinic and daytime ambulatory BP on entry were 181/79 + /- 21/9 mm Hg and 165/82 + /- 23/15 mm Hg , respectively . All drugs reduced mean casual and ambulatory BP significantly relative to placebo but only hydrochlorothiazide and enalapril produced a consistent hypotensive effect throughout the entire 24-hour period . Isradipine and enalapril exhibited a relatively greater effect on reducing systolic BP than either hydrochlorothiazide or atenolol . ( ABSTRACT TRUNCATED AT 250 WORDS This study evaluated the anti-hypertensive efficacy , tolerability and effects on left ventricular mass of losartan , a selective angiotensin II receptor antagonist , after 22 months in patients with essential hypertension . The study included 77 hypertensive patients who were r and omised at baseline to 22 months double-blind once-daily treatment with losartan 50 mg ( L group n = 44 patients , mean age 54 ± 9 years ) or hydrochlorothiazide 25 mg ( HCTZ group , n = 33 patients , mean age 56 ± 7 years ) . Routine haematology , blood chemistry , st and ard electrocardiography , echocardiography and ambulatory non-invasive 24-h blood pressure ( BP ) monitoring were performed at baseline and after 10 and 22 months . The results showed good tolerability and a significant mean systolic and diastolic BP reduction in all groups ( L group : 22 mm Hg and 11 mm Hg ; HCTZ group : 11 mm Hg and 7 mm Hg , respectively for systolic and diastolic mean BP ) . Moreover , a remarkable reduction in left ventricular mass index was reached after 10 and 22 months only in the L group ( L group : Δ = –11 g/m2 , P < 0.02 ; hctz group : δ = –5 g/m2 , P = 0.38 ) . In conclusion , losartan was well tolerated and produced a significant reduction in BP and left ventricular mass in hypertensive 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 The antihypertensive effects of four different antihypertensive medications ( beta-blocking agent , atenolol 50 mg ; calcium-antagonist , isradipine SRO [ slow release ] 2.5 mg ; diuretic , hydrochlorothiazide [ HCTZ ] 25 mg ; and angiotension converting enzyme-inhibitor , spirapril 6 mg ) on obese patients with sleep disordered breathing and hypertension were compared by the ambulatory blood pressure measurement ( ABPM ) . Eighteen patients were r and omized in a double-blind , crossover fashion to receive each of the four different medications for 8 weeks . ABPM was performed at baseline and after an 8-week treatment with these medications . A 2- to 3-week washout period occurred both at baseline and between each of the four medications . Three patients were omitted from statistical analysis because of technical problems of ABPM .  Atenolol , isradipine SRO , and spirapril  decreased significantly ( P < .01 ) the mean 24-h systolic blood pressure , whereas HCTZ did not . The mean 24-h diastolic blood pressure decreased significantly after all four medications : 12 ( SD+/-14 ) mm Hg with atenolol , 7 ( SD+/-10 ) mm Hg with isradipine SRO , 3 mm Hg ( SD+/-14 ) with HCTZ , and 6 ( SD+/-15 ) mm Hg with spirapril ( P < .01 ) . During nighttime none of the medications reduced the mean diastolic or systolic blood pressure significantly . According to the 24-h blood pressure curve the influence of these four medications during the whole measurement period was not similar .  Atenolol  and spirapril lost their antihypertensive effect during the early morning hours . The antihypertensive effect of HCTZ varied markedly from hour to hour . The trough-to-peak ratio of no medication was > 0.50 . Negative correlation was observed between the apnea time and the mean systolic 24-h ( r = -0.604 , P = NS ) and the mean systolic nocturnal blood pressure change ( r = -0.590 , P = NS ) . Our study revealed that the daytime high blood pressure was quite easily controlled by the ordinary monotherapy in these patients with partial upper airway obstruction and hypertension . Instead none of the medications used decreased nocturnal high blood pressure markedly BACKGROUND Blood pressure ( BP ) is controlled by a variety of systems , the activities of which vary throughout the day . As drugs are developed that selectively block these systems , the fall in BP may not be consistent over 24 h. METHODS A total of 24 patients ( aged > 65 years ) with systolic BP ( SBP ; > 150 mm Hg ) that had not been treated entered a sub study of a larger study performed in 74 patients . In a double blind , crossover study with a balanced design , they received placebo , atenolol 50 mg , perindopril 8 mg , felodipine 10 mg , or hydrochlorothiazide 50 mg . The study periods were 2 months . Ambulatory BP monitoring was performed at the end of each period , and was divided into awake periods ( 9:00 AM to 10:00 PM ) , sleep periods ( 12:00 AM to 6:00 AM ) , and morning periods ( 6:00 AM to 9:00 AM ) . Medication was taken at 9:00 AM . RESULTS The four drug classes lowered 24-h mean SBP ( P < .05 ) , but the fall with atenolol was less than with the other drugs . The fall in awake BP with perindopril was less than with felodipine or hydrochlorothiazide . Atenolol caused no significant fall in sleep or morning SBP , and the falls with the other three drugs were significant and were greater than the fall with atenolol . The fall in sleep BP with perindopril was greater than with the other drug classes . The awake-sleep difference in SBP increased with perindopril , stayed the same with felodipine and hydrochlorothiazide , and was reduced by atenolol . CONCLUSIONS In this study , the response to the different drug classes differed . The response to drugs that work relatively nonspecifically ( diuretics , calcium blockers ) was relatively consistent over 24 h. The response to beta blockers and to angiotensin converting enzyme inhibitors reflected the activity of control systems . This finding supports the concept of multiple drug therapy that may need to be tailored to the time of day Objective To compare with placebo the efficacies of once-daily administrations of lacidipine and hydrochlorothiazide separately and in combination to elderly patients with systolic hypertension . Design and methods Nineteen elderly subjects ( five men and 14 women , median age 71 years , range 62–79 years ) participated in the study , which had a r and omized double-blind crossover design . For each subject there were four treatment phases , each of duration 4 weeks . The initial treatments in each phase were 2 mg lacidipine once a day and 25 mg hydrochlorothiazide once a day , separately and in combination , and placebo . Doses of each agent could be doubled after 2 weeks in each phase if the patient 's goal systolic blood pressure had not been achieved . The numbers of subjects administered the higher dose of each treatment were 13 for placebo , 14 for lacidipine , 11 for hydrochlorothiazide and eight for lacidipine plus hydrochlorothiazide .  Results End-of-phase mean clinic blood pressures were 164/85 mmHg with placebo , 159/82 mmHg with lacidipine , 157/84 mmHg with hydrochlorothiazide and 152/82 mmHg with lacidipine plus hydrochlorothiazide . Systolic blood pressure was significantly reduced during all active treatment phases compared with placebo and that for the lacidipine plus hydrochlorothiazide phase was also significantly less than those for both of the other active treatment phases . There was no difference between sitting and st and ing blood pressure for any phase . Factorial analysis of the main effects of treatment indicated that the effects of lacidipine and hydrochlorothiazide on clinic blood pressure were additive and also that heart rate was higher when hydrochlorothiazide had been administered . Ambulatory blood pressure monitoring confirmed the pattern of the responses of blood pressure and showed that administration of hydrochlorothiazide had a significantly greater effect on systolic blood pressure and a longer duration of action than did administration of lacidipine . There was no difference in the frequency of adverse effects among any of the phases . Conclusions In treating elderly systolic hypertensives the diuretic hydrochlorothiazide is a more effective antihypertensive agent with a longer duration of action than is the calcium channel antagonist lacidipine . In combination the effects of these two drugs on blood pressure are additive Objective Individual blood pressure responses to antihypertensive therapy are difficult to predict . To improve optimization of antihypertensive therapy , we analyzed correlations of relevant laboratory tests with blood pressure responses to four antihypertensive monotherapies . Methods In the GENRES study , 208 Finnish men aged 35–60 years with moderate hypertension used amlodipine 5 mg , bisoprolol 5 mg , hydrochlorothiazide 25 mg and losartan 50 mg daily , each for 4 weeks as a monotherapy in a double-blind , r and omized , placebo-controlled crossover study ; that is , each subject received each type of monotherapy in a r and om order . The treatment periods were preceded and separated by 4-week placebo periods . Ambulatory 24-h and office blood pressure measurements were carried out after all study periods . Data from several biochemical tests were correlated to antihypertensive drug responses . Results Serum total calcium concentration was negatively correlated with blood pressure responses to amlodipine ( P values 0.001–0.002 ) . Plasma renin activity was positively correlated with blood pressure responses to losartan ( P values 0.001–0.005 ) and bisoprolol ( P values 0.03–0.17 ) , and negatively with blood pressure responses to hydrochlorothiazide ( P values 0.01–0.07 ) . Daily urinary excretion of sodium was negatively correlated with ambulatory blood pressure responses to amlodipine ( P values 0.001–0.01 ) . Conclusions In this carefully controlled study , marked individual variations in antihypertensive drug responsiveness were found to correlate to several baseline laboratory parameters . The negative correlation between serum calcium levels and amlodipine responses is intriguing and suggests an underlying mechanistic association . Collectively , our data imply that laboratory tests may have some value in prediction of the efficacy of various antihypertensive drug therapies , although great patient-to-patient variation remains an obstacle for exact predictive classification Background and Purpose — The Plaque Hypertension Lipid-Lowering Italian Study ( PHYLLIS ) tested whether ( 1 ) the angiotensin-converting enzyme ( ACE ) inhibitor fosinopril ( 20 mg per day ) was more effective on carotid atherosclerosis progression than the diuretic hydrochlorothiazide ( 25 mg per day ) , ( 2 ) pravastatin ( 40 mg per day ) was more effective than placebo when added to either hydrochlorothiazide or fosinopril , and ( 3 ) there were additive effects of ACE inhibitor and lipid-lowering therapies . Methods — A total of 508 hypertensive , hypercholesterolemic patients with asymptomatic carotid atherosclerosis were r and omized to : ( A ) hydrochlorothiazide ; ( B ) fosinopril ; ( C ) hydrochlorothiazide plus pravastatin ; and ( D ) fosinopril plus pravastatin , and followed up blindly for 2.6 years . B-Mode carotid scans were performed yearly by certified sonographers in 13 hospitals and read central ly . Corrections for drift were calculated from readings repeated at study end . Primary outcome was change in mean maximum intima-media thickness of far and near walls of common carotids and bifurcations bilaterally ( CBMmax ) . Results — CBMmax significantly progressed ( 0.010±0.004 mm per year ; P=0.01 ) in group A ( hydrochlorothiazide alone ) but not in groups B , C , and D. CBMmax changes in groups B , C , and D were significantly different from changes in group A. Changes in group A were concentrated at the bifurcations . “ Clinic ” and “ ambulatory ” blood pressure reductions were not significantly different between groups , but total and low-density lipoprotein cholesterol decreased by ≈1 mmol/L in groups C and D. Conclusions — Progression of carotid atherosclerosis occurred with hydrochlorothiazide but not with fosinopril . Progression could also be avoided by associating pravastatin with hydrochlorothiazide
target: 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
background: 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 .