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Nonselective nonsteroidal anti-inflammatory agents have been shown to attenuate the antihypertensive efficacy of ACE inhibitors with average increases in systolic blood pressure ( BP ) of 5 to 10 mm Hg . Less is known about the specific cyclooxygenase-2 ( COX-2 ) inhibitors now widely used for the treatment of arthritis . The objective of this study was to determine the effects of celecoxib compared with placebo on 24-hour BP levels in ACE inhibitor-treated patients with hypertension . This was a r and omized , double-blind , placebo-controlled , parallel-group clinical trial involving 178 men and women ( mean age , 53 years ) with essential hypertension who were treated and controlled with lisinopril monotherapy ( 10 to 40 mg daily ) .  Baseline BP values were obtained using 24-hour ambulatory recordings . Patients received either celecoxib , 200 mg twice daily ( twice the recommended dose for osteoarthritis ) ( n=91 ) , or placebo ( n=87 ) for 4 weeks , and changes in the 24-hour BP , body weight , and clinical laboratory parameters were assessed . Mean changes from baseline in the 24-hour systolic and diastolic BP were 2.6/1.5±0.9/0.6 mm Hg on celecoxib versus 1.0/0.3±1/0.6 mm Hg on placebo ( P = 0.34 for systolic BP;P = 0.45 for diastolic BP ) . The proportion of patients whose 24-hour BP increased by at least 5 , 10 , 15 , or 20 mm Hg were also similar on celecoxib and placebo . No changes in body weight , serum creatinine , or potassium occurred in either group . Thus , these data demonstrate that high doses of celecoxib have no significant effect on the antihypertensive effect of the ACE inhibitor lisinopril . The placebo-subtracted changes observed in 24-hour BP ( 1.6/1.2 mm Hg ) are less than what has been reported for nonselective nonsteroidal anti-inflammatory agents in ACE inhibitor-treated patients The ability of angiotensin converting enzyme ( ACE ) inhibitors to lower blood pressure may in part be due to the formation of vasodilatory prostagl and ins . Inhibition of prostagl and in synthesis with aspirin may therefore theoretically attenuate the antihypertensive effect of ACE inhibitors . This trial studied the interaction between aspirin ( ASA ) and enalapril , an ACE inhibitor , and ASA and losartan , an angiotensin subtype 1 receptor antagonist .  Seventeen essential hypertensive patients were studied , maintained on a stable dose of either enalapril ( n = 7 ) or losartan ( n = 10 ) monotherapy for > or = 12 weeks before and throughout the study . Each patient received a 2-week course of placebo , 81 mg/day ASA , and 325 mg/day ASA , each treatment separated by a 2-week washout period . Blood pressure ( BP ) and serum thromboxane B2 ( TXB2 ) sample s were obtained at the end of each treatment period . Placebo was compared with each dose of ASA for each group . In both the enalapril and losartan groups , mean , systolic , and diastolic BP were unchanged with the addition of ASA .  Concentrations of TXB2 were suppressed to < 10 % in both groups with ASA . This study demonstrates that 81 to 325 mg/day ASA exerts no significant effect on BP in essential hypertensives taking enalapril or losartan The  efficacy and tolerability of eplerenone , a selective aldosterone blocker , was assessed when added to existing antihypertensive therapy with an ACE inhibitor or an angiotensin II receptor blocker ( ARB ) . Hypertensive patients ( n=341 ) whose blood pressure ( BP ) was not controlled despite ACE inhibitor or ARB  were r and omized ( double-blind ) to receive 50 mg eplerenone ( increasing to 100 mg if required ) once daily or placebo for 8 weeks . Diastolic and systolic BP and adverse events were recorded . By study end ( week 8) , mean seated diastolic BP was significantly reduced from week 0 among patients receiving eplerenone/ARB ( −12.7±0.81 mm Hg ) compared with those receiving placebo/ARB ( −9.3±0.83 mm Hg ) . The change in mean seated diastolic BP was −9.9±0.88 mm Hg in eplerenone/ACE inhibitor patients and −8.0±0.86 mm Hg in placebo/ACE inhibitor patients ( P = NS ) . Systolic BP levels were also significantly lower at week 8 for eplerenone/ACE inhibitor ( −13.4±1.35 mm Hg ) and eplerenone/ARB ( −16.0±1.37 mm Hg ) patients , respectively , compared with placebo/ACE inhibitor ( −7.5±1.31 mm Hg ) and placebo/ARB patients ( −9.2±1.41 mm Hg ) . Adverse events were generally nonsevere and not significantly different between eplerenone and placebo . This study demonstrated that in patients whose BP was not controlled with an ACE inhibitor or ARB , the addition of eplerenone over an 8-week period significantly lowered systolic BP in both groups and diastolic BP in ARB patients . Selective aldosterone blockade with eplerenone , therefore , may be useful add-on therapy in hypertensive patients inadequately controlled on ACE inhibitor or ARB alone Recent studies showed that in diabetic hypertensive patients , administration of angiotensin-converting enzyme (ACE)-inhibitors or calcium antagonists can effectively lower blood pressure ( BP ) and prevent diabetes-related cardiovascular complications with no adverse metabolic effects . We sought to assess the antihypertensive and metabolic effects of the new dihydropyridine calcium antagonist manidipine ( M ) in patients with diabetes mellitus and essential hypertension as compared with the ACE inhibitor enalapril ( E ) . After 3 weeks of placebo , 101 ( 62 men ; age range , 34 - 72 years ) hypertensives with type II diabetes mellitus were r and omized to M 10 - 20 mg or E 10 - 20 mg , od , for 24 weeks . At the end of the placebo period and the active-treatment phase , BP was measured with a mercury sphygmomanometer ( office , O ) and over the 24 h by ambulatory ( A ) monitoring . ABP recordings were analyzed to obtain 24-h , day ( 6 a.m. to midnight ) , and night ( midnight to 6 a.m. ) average systolic ( S ) and diastolic ( D ) BP and heart rate ( HR ) values . Homogeneity of the antihypertensive effect over the 24 h was assessed by the smoothness index [ SI : i.e. , the ratio between the average of the 24 hourly BP changes after treatment and the corresponding st and ard deviation ( the higher the SI , the more uniform is the BP control by treatment over the 24 h ] . The O SBP and DBP were significantly ( p < 0.01 ) and similarly reduced by M ( 16 + /- 10 and 13 + /- 6 mm Hg , n = 49 ) and E ( 15 + /- 10 and 13 + /- 6 mm Hg , n = 45 ) . The percentage of patients whose O DBP was reduced < or = 85 mm Hg ( i.e. , the value indicated to be the optimal DBP goal in diabetic hypertensives ) was similar for M ( 37 % ) and E ( 40 % ) . The reduction of 24-h BP also was similar between M ( n = 38 ) and E ( n = 38 ) for both drugs ( systolic , 6 + /- 11 and 8 + /- 10 mm Hg ; diastolic , 5 + /- 8 and 5 + /- 7 ; NS , M vs. E ) . The antihypertensive effect was distributed in a similar homogeneous fashion throughout the dosing interval , as shown by the similar SI values ( M , 0.6 + /- 1.2 for SBP and 0.6 + /- 0.9 for DBP ; E , 0.6 + /- 0.8 for SBP and 0.5 + /- 0.7 for DBP ; NS , M vs. E ) . O and A HR were unchanged by either treatment . Markers of glucose and lipid metabolism and renal function were not significantly modified by treatment both with M and with E. In the diabetic hypertensives , M was as effective and metabolically neutral as the ACE-inhibitor BACKGROUND Although beta-blockers and angiotensin-converting enzyme ( ACE ) inhibitors are often used together , there is a lack of quantitative evidence for the efficacy of this combination in reducing  blood pressure ( BP ) .  OBJECTIVE The aim of this r and omized , double-blind , placebo-controlled , crossover study was to quantify the combined effect of a beta-blocker ( atenolol ) and an ACE inhibitor ( lisinopril ) in lowering BP . METHODS Participants who were > or = 40 years of age and enrolled in the hypertension or anticoagulation clinics at St. Bartholomew 's Hospital , London , United Kingdom , were r and omized to 3 consecutive 4-week treatments consisting of atenolol 25 mg plus placebo , lisinopril 5 mg plus placebo , and atenolol 25 mg plus lisinopril 5 mg , plus a period of 2 placebos . At the end of each period , seated BP was measured in the right arm using electronic monitors . RESULTS The mean  placebo-adjusted peak BP reductions among the 47 participants ( mean age , 62 [ range 42 - 82 ] years ; 75 % male ; 70 % white/30 % Asian ; mean baseline BP , 145/82 mm Hg ) who completed all 4 periods were significantly greater with the combination of both drugs than with either drug alone ( P < 0.001 ) . The systolic reductions were 22.9 mm Hg with combination treatment , 16.1 mm Hg with atenolol treatment , and 12.5 mm Hg with lisinopril treatment , and the diastolic reductions were 13.9 , 9.8 , and 6.8 mm Hg , respectively . The BP-lowering effect of the 2 drugs together was similar to that expected from the sum of each alone , allowing for the reduced effect of 1 drug given the lower pretreatment BP due to the other . The incremental systolic BP reduction from the 2 drugs together compared with 1 alone was 79 % ( 95 % CI , 54%-126 % ) of the expected additive effect , 88 % ( 95 % CI , 58%-130 % ) for diastolic BP , and 84 % ( 95 % CI , 65%-118 % ) for the mean of systolic and diastolic BP . CONCLUSIONS The combination of the beta-blocker atenolol 25 mg plus the ACE inhibitor lisinopril 5 mg was associated with a significantly greater decrease in BP compared with either alone . The BP reduction with the combination treatment was similar to and statistically consistent with the 2 drugs having additive effects . Clinical Trials Identification Number : IS RCT N97280940 BACKGROUND Antihypertensive agents differentially influence the plasma adiponectin concentration and the effects of fixed-dose combination regimens remain unclear . The influence of a combination of an angiotensin-converting enzyme inhibitor ( ACEI ) and a thiazide-type diuretic or an ACEI alone on plasma adiponectin concentrations in patients with essential hypertension was evaluated in the present study . METHODS AND RESULTS After a 2-week placebo run-in phase , 30 patients with essential hypertension were r and omized to receive preterax ( 2 mg perindopril/0.625 mg indapamide ) or cilazapril ( 2.5 mg ) once daily for 12 weeks . Plasma adiponectin and insulin concentrations were measured before and after treatment . Insulin resistance was measured by homeostasis assessment index ( HOMA-IR ) . Treatment with preterax ( P=0.003 ) and cilazapril ( P=0.031 ) significantly reduced systolic blood pressure ( BP ) , but only preterax reduced diastolic BP ( P=0.024 ) . Cilazapril treatment significantly increased the plasma adiponectin concentration ( P=0.025 ) and reduced plasma triglycerides ( P=0.041 ) , whereas preterax treatment increased the plasma insulin concentration ( P=0.041 ) and tended to increase HOMA-IR . CONCLUSIONS The combination of an ACEI and indapamide improved BP control , but attenuated the beneficial effects of ACE inhibition on plasma adiponectin in patients with essential hypertension . Such a combination may be best reserved for improved BP control rather than for metabolic protection in clinical hypertension OBJECTIVES This dose-ranging study evaluated the antihypertensive efficacy and tolerability of aliskiren in patients with mild-to-moderate hypertension . BACKGROUND Low blood pressure ( BP ) control rates among patients with hypertension indicate a need for improved treatment options . This study investigates aliskiren , the first in a new antihypertensive class called renin inhibitors . METHODS Patients with mean sitting diastolic BP 95 to 109 mm Hg were r and omized to aliskiren 150 , 300 , or 600 mg or placebo  once daily for 8 weeks . Patients completing this treatment phase entered a 2-week treatment-free withdrawal period . Office BP was recorded at baseline , weeks 2 , 4 , 6 , and 8 of treatment , and 4 days and 2 weeks after cessation of treatment . A subgroup of patients underwent ambulatory BP monitoring . RESULTS In total , 672 patients were r and omized to treatment . After 8 weeks , aliskiren 150 , 300 , and 600 mg significantly reduced mean sitting BP ( systolic/diastolic ) by 13.0/10.3 , 14.7/11.1 , and 15.8/12.5 mm Hg , respectively , versus 3.8/4.9 mm Hg with placebo ( all p < 0.0001 for systolic and diastolic BP ) . The BP-lowering effect of aliskiren persisted for up to 2 weeks after treatment withdrawal . Aliskiren significantly reduced mean 24-h ambulatory BP ( p < 0.0001 vs. placebo with all doses ) exhibiting smooth , sustained effects and high trough-to-peak ratios .  Aliskiren was well tolerated ; overall adverse event rates were 40.1 % , 46.7 % , and 52.4 % with aliskiren 150 , 300 , and 600 mg , respectively , and 43.0 % with placebo . Few patients discontinued treatment due to adverse events . CONCLUSIONS Aliskiren provides significant antihypertensive efficacy in patients with hypertension , with no rebound effects on blood pressure after treatment withdrawal Objective The aim of this open multicentric study was to investigate the efficacy and safety of the addition of an angiotensin converting enzyme ( ACE ) inhibitor ( benazepril , 10 mg/day ) or a diuretic ( hydrochlorothiazide , 12.5 mg/day ) for 4 weeks in patients with mild to moderate essential hypertension having been treated for 4 weeks by an angiotensin II antagonist ( valsartan , 80 mg/day ) but still having a diastolic blood pressure ( BP ) > 90 mmHg on this medication given alone . Methods A total of 327 patients were included in the trial and 153 patients ( 46 % ) had their diastolic BP ⩽ 90 mmHg after 4 weeks of valsartan monotherapy . These patients continued the same treatment regimen for the next 4 weeks , but no further blood pressure reduction was observed . The remaining patients were r and omized to either the valsartan – hydrochlorothiazide or the valsartan – benazepril combination . Results The two combinations induced an additional significant BP reduction , which was of similar magnitude for diastolic BP ( −4.5 during valsartan – hydrochlorothiazide treatment and −3.3 mmHg during valsartan – benazepril treatment ) , but of greater magnitude for systolic BP during valsartan – hydrochlorothiazide ( −6.77 mmHg ) than during valsartan – benazepril co-administration ( −3.2 mmHg ) . At the end of the trial , the BP of the responders to the valsartan monotherapy was lower than that of patients having required a combination therapy . Valsartan given alone or in association with hydrochlorothiazide or benazepril was well tolerated . Conclusion These data therefore show that in patients not responding sufficiently to angiotensin II receptor blockade BP can be further and safely lowered by adding a small dose of a diuretic or an ACE inhibitor , with the diuretic-containing combination tending to being more effective in controlling systolic BP Background Angiotensin-converting enzyme ( ACE ) inhibitors and angiotensin receptor blocking drugs ( ARB ) block the effect of angiotensin II by different mechanisms . It has been suggested that combined therapy may be more effective at reducing blood pressure ( BP ) than higher doses of either drug . Methods Twenty-three elderly patients with systolic hypertension completed a double-blind crossover study comparing placebo , c and esartan ( C ) 16 mg , C32 mg , lisinopril ( L ) 20 mg , L40 mg and C16 mg + L20 mg . Treatment periods were one month and ambulatory BP measurements were performed at the end of each period . The effects on albumin excretion in eight patients with microalbuminuria  were determined . Results All treatments lowered BP . The falls in systolic and diastolic BP with C16 , C32 , L20 and L40 were similar . Plasma renin rose to a similar extent . A plateau effect was reached with C16 and L20 . Systolic BP on the combination of C16 + L20 was lower than on each monotherapy ( C16 , 3.8 mmHg [ p=0.002 ] ; C32 , 6.4 [ 0.0003 ] ; L20 , 2.9 [ 0.05 ] ; L40 , 3.3 [ 0.003 ] ) . The additional fall in BP with the combination appeared to be due to recruitment of non-responders , rather than to an additive effect in most patients . All treatments reduced microalbuminuria to a similar extent . The combination was well tolerated and there was no deterioration in renal function . Conclusion When patients are on a plateau dose of an ACE inhibitor or an ARB , addition of the other drug class has a small but significant incremental effect on BP in the overall group . However , some patients respond better to one drug class than to the other and this may explain the results . This study lends no support to the use of these two drugs in combination to treat hypertension To assess the efficacy and time-dependent effects of once-daily moexipril , a nonsulfhydryl ester prodrug of the angiotensin-converting enzyme ( ACE ) inhibitor , moexiprilat , we conducted a multicenter , double-blind , placebo-controlled trial in 51 hypertensive patients using both clinic and ambulatory blood pressure ( BP ) recordings . Patients were included in the trial based on a minimum of 40 % of the daytime diastolic BPs of 90 mm Hg or more during a placebo baseline phase ; and the primary endpoint was change in  24-hour ambulatory diastolic BP .  Patients were r and omized to receive placebo , 7.5 mg of moexipril , or 15 mg of moexipril once daily . Clinic and ambulatory BPs were taken on the first day and after eight weeks of double-blind therapy . After the 7.5-mg dose , there were no significant changes in the acute or prolonged clinic BPs compared with placebo . Compared with adjusted mean changes for placebo , the 15-mg moexipril dose lowered clinic systolic BP , but not diastolic BP . In contrast , acute ( 1 day ) reductions in 24-hour diastolic BPs were -2/-3 mm Hg , -6/-4 mm Hg , and -14/-9 mm Hg on placebo , 7.5 mg of moexipril , and 15 mg of moexipril , respectively ( P < .01 for the 15-mg dose ) . Similarly , after long-term dosing for 8 weeks , reductions in 24-hour diastolic BPs were 1/-2 mm Hg , -6/-4 mm Hg , and -12/-9 mm Hg for the respective treatment groups ( P < .01 for the 15-mg dose ) . ( ABSTRACT TRUNCATED AT 250 WORDS The study was design ed to assess the antihypertensive effect of combined angiotensin-converting enzyme ( ACE ) inhibition and angiotensin II type 1 receptor ( AT1 ) antagonism in patients with essential hypertension . Twenty patients with uncontrolled ambulatory diastolic blood pressure ( BP ) after 6 weeks of ACE inhibitor monotherapy ( benazepril , 20 mg , o.d . ) were r and omized to receive double-blind valsartan , 80 mg , o.d . ( AT1 antagonist ) or matching placebo for 5 weeks while continuing to receive background benazepril . Then patients crossed over to the alternative regimen for a second 5-week period . The 24-h ambulatory BP was monitored on the final day of the benazepril monotherapy period and on the final day of each double-blind treatment period . Valsartan added to benazepril produced a significant antihypertensive effect with a benefit over placebo of 6.5 + /- 12.6/4.5 + /- 8.0 mm Hg ( systolic/diastolic ) for average awake ambulatory BP ( p < 0.05 ) , 7.1 + /- 9.4/5.6 + /- 6.5 mm Hg for asleep BP ( p < 0.01 ) , and 6.8 + /- 9.7/4.9 + /- 6.8 mm Hg for average 24-h ambulatory BP ( p < 0.01 ) . Pulse rate was unaffected . Plasma active renin was higher on the benazepril-valsartan combination compared with benazepril-placebo ( p < 0.05 ) . There was no change in routine biochemical variables when valsartan was added to benazepril . Six patients reported mild dizziness or fatigue ( three also with placebo ) . These data suggest that in hypertensive patients uncontrolled with an ACE inhibitor , the addition of an AT1 antagonist provides a powerful and safe antihypertensive drug combination Aims of our study were i ) to compare in a large number of hypertensive subjects the relative effect of antihypertensive treatment on clinic ( C ) blood pressure ( BP ) and various ambulatory ( A ) BP components , and ii ) to determine whether antihypertensive treatment affects BP variability . In 266 mild essential hypertensive out patients ( age : 18 - 78 years )  CBP ( trough measurements ) and ABP  ( Spacelabs 90202 or 90207 ) were measured after 3 to 4 weeks of wash-out and after 4 to 8 weeks of treatment with an ACE-inhibitor ( n = 135 ) or a calcium-antagonist ( n = 131 ) . ABP recordings were analyzed to obtain average 24 h , day-time ( 6 a.m. to midnight ) and night-time ( midnight to 6 a.m. ) systolic and diastolic BP values and st and ard deviations ( BP variabilities ) . Treatment reduced both CBP and ABP . Treatment-induced changes in CBP showed a poor correlation with those in 24h , day- and night-time BP ( r never > 0.23 ) and the correlation was poor also when trough ABP ( mean of last 2 h ) was considered . Twenty-four hour , day- and night-time BP were similarly reduced by treatment with a direct relationship between the initial BP values and the subsequent BP falls . BP st and ard deviations were also reduced by treatment in relation to the pretreatment values but the overall reduction was small , limited to the day-time and proportional or less than proportional to the reduction in mean values , with no changes or an increase in variation coefficients . The effects of ACE-inhibitor and calcium-antagonist treatments were superimposable . Our results from a large data base show that antihypertensive treatment effectively reduces all ABP components . The reduction can not be predicted by the concomitant fall in CBP but it relates to the initial ABP values . Treatment has a limited effect on BP variability , this being the case both for ACE-inhibitors and calcium-antagonists A factorial design was applied in this multicenter , double-blind , placebo-controlled trial of the calcium-channel blocker verapamil and the ACE inhibitor enalapril to assess the hypotensive effects of the combination compared with monotherapy , to evaluate safety , and to determine the effects on quality of life ( QOL ) of both drugs , alone and in combination . The study consisted of a 3 x 2 factorial design wherein 186 men and women with a sitting diastolic blood pressure ( BP ) of between 95 mm Hg and 114 mm Hg , after a 4-week placebo washout , were r and omized to one of six treatment groups for 4 weeks of active treatment . Monotherapy with both 240 mg verapamil and 10 mg enalapril reduced systolic and diastolic BP to a similar extent and significantly more than placebo . The 240 mg verapamil + 10 mg enalapril combination was additive for both systolic and diastolic blood pressure ; 120 mg verapamil + 10 mg enalapril was additive for systolic BP only . The total number of adverse events reported was similar for all six treatment groups . QOL scores were unchanged from baseline and not different between treatment groups . The combination of 240 mg verapamil and 10 mg enalapril was significantly more effective at reducing BP than either drug alone ; this additivity of effect was not linked to a higher rate of adverse experiences or to a deterioration in QOL . Thus , combination therapy at lower doses may offer an alternative treatment option to higher dose monotherapy Arthritis and hypertension are frequent comorbidities in the elderly hypertensive population .  Nonsteroidal anti-inflammatory drugs are often used to relieve pain in arthritic patients but a side effect is sodium retention and consequent elevation of blood pressure ( BP ) . The effect of dihydropyridine calcium blocking drugs is relatively independent of sodium intake , whereas the angiotensin-converting enzyme ( ACE ) inhibitors ' effects can be blunted by a high-sodium diet . This study compared the effects of indomethacin with placebo in elderly patients with essential hypertension who had been controlled with amlodipine or enalapril . Indomethacin 50 mg twice daily or placebo was administered for 3 weeks in a double-blind crossover study to patients controlled with amlodipine or enalapril . The response was assessed by ambulatory BP measurement .  Indomethacin  raised BP and lowered pulse rates in patients taking enalapril but had little effect in patients receiving amlodipine . The difference caused by indomethacin between the two groups was 10.1/4.9 mm Hg increase in BP and a 5.6 beats/min fall in pulse in people taking enalapril . Addition of indomethacin to patients taking either drug caused a rise in weight and a fall in plasma renin . It is postulated that the effect is due to inhibition of prostagl and in synthesis , which causes sodium retention . In patients taking amlodipine , the fall in plasma renin ameliorates the effect of sodium retention on BP . In patients taking enalapril , plasma renin falls but this is not translated into an effect because of the blockage of converting enzyme . Thus , the full effect of sodium retention on BP is expressed . In patients treated with indomethacin , fewer patients may respond to ACE inhibitors . However , the major problem is the patient who intermittently takes indomethacin or other nonsteroidal anti-inflammatory drugs , which , if a person is treated by an ACE inhibitor causes BP to go out of control . In such patients amlodipine would appear to be a preferred choice to enalapril The Hypertension Objective Treatment Based on Measurement by Electrical Devices of Blood Pressure ( HOMED-BP ) Study is the first large-scale intervention trial in Japan using a PROBE design to determine an optimal target blood pressure ( BP ) level on the basis of self-measured BP at home and optimal initial antihypertensive medication . The registered patients are r and omized to one of two different BP levels and to initial antihypertensive regimens ( i.e.  ,  calcium antagonist [ Ca-A ] , angiotensin-converting enzyme inhibitor [ ACE-I ] , or angiotensin II receptor antagonist [ ARB ] ) . At the end of February 2004 , 2729 , 1687 , and 971 patients were recruited , r and omized , and followed-up for 12 months or more . Among the 971 patients , mean systolic/diastolic BP levels at r and omization in the Ca-A , ACE-I , and ARB groups were 150/90 , 152/89 , and 151/89 mmHg , respectively . These values reduced after six months of Ca-A- , ACE-I- , and ARB-based treatment ( 133/81 mmHg , 135/80 mmHg , and 134/79 mmHg , respectively ) and further reduced after 12 months ( 131/80 mmHg , 134/79 mmHg , and 132/79 mmHg , respectively ) without any significant differences among groups . In more intensive and less intensive BP-lowering groups , mean systolic/diastolic BP levels at r and omization were 151/90 and 150/89 mmHg , respectively . Although BP levels reduced after 6-month ( 135/80 mmHg and 133/80 mmHg , respectively ) and 12-month treatment ( 133/79 mmHg and 132/80 mmHg , respectively ) in each target group , no significant difference in BP values was observed between groups . These results indicate the necessity of additional interventional strategies to improve the achievement of target BP levels , especially in the more intensive BP-lowering group The objective of this study was to determine which of the common groups of antihypertensive drugs is most effective at lowering systolic blood pressure ( SBP ) in elderly patients with previously untreated hypertension and the percentage of patients controlled with single or sequential monotherapy . Subjects were recruited from patients attending other outpatient clinics and entered into the study if their SBP was more than 150 mm Hg after three visits . Patients were given a low and high dose of each of the main classes of drugs or placebo for 1 month each . The study was a balanced , r and omized crossover design with five periods : placebo ; angiotensin converting enzyme inhibitors ; beta-blocking drugs ; calcium-blocking drugs ; and thiazide diuretics .  Blood pressure ( BP ) was measured 24 to 26 h after the previous dose . A question naire for side effects was administered at each visit . Seventy-four patients entered the study . beta-Blockers could not be used in 15 patients because of asthma or bronchospasm and these had two placebo periods . There were 9 of 66 patients on P , 9 of 46 on beta-blockers , 4 of 65 on calcium-blocking drugs , 4 of 65 on diuretic , and 1 of 62 patients on ACE inhibitors who did not progress to the higher dose because of side effects . Decreases in SBP compared to r and omized placebo were calcium-blocking drugs 15 mm Hg = diuretic 13 mm Hg > ACE inhibitors 8 mm Hg = beta-blockers 5 mm Hg . Blood pressure decrease correlated with placebo BP ( P < .0005 , r = 0.53 to 0.70 ) . When corrected for placebo , target SBP ( < 140 mm Hg ) was reached in between 6 % to 15 % of patients on monotherapy . Sequential monotherapy achieved target in 29 % . Angiotensin converting enzyme inhibitors , calcium-blocking drugs , and diuretics had no more side effects than placebo . Patients on beta-blockers had more side effects and the well-being score was reduced . Diuretics and calcium-blocking drugs are more effective in elderly patients at lowering SBP pressure . beta-Blockers were relatively ineffective , were frequently contraindicated , and had more side effects . Monotherapy achieved control in only a small number of patients . In elderly people with essential hypertension , therapy should be instituted with diuretics or calcium-blocking drugs , but combination therapy will usually be required to achieve goal Abstract Inhibition of the angiotensin-converting enzyme ( ACE ) exerts a renoprotective effect in adult patients with chronic kidney disease . We evaluated prospect ively changes in blood pressure ( BP ) , protein excretion and renal function after administration of the long-acting ACE inhibitor ramipril as monotherapy during 6 months in 14 moderately hypertensive children aged 5–18 years with various nephropathies . Four patients initially had a decreased glomerular filtration rate ( GFR below 60 ml/min/1.73 m2 ) . BP was evaluated by ambulatory 24-h monitoring . After 2 weeks of treatment by oral ramipril ( 1.5 mg/m2 once daily ) , mean values of systolic and diastolic 24-h ambulatory BP fell by more than 5 mmHg in nine patients . In eight patients the dose was doubled . At the end of the study systolic BP was below the 95th percentile in 9 and diastolic BP in 13 patients . The initially reduced nocturnal dip increased significantly . Of 11 patients with an increased albumin excretion ( median 1.3 g/g creatinine ) , 6 responded to ramipril by a median reduction of 78 % ( range 24–83 % ) , whilst in 5 albuminuria increased ( median + 19 % ) . GFR was well preserved and no other adverse effects from the drug were noted . The study demonstrates that ramipril is an efficacious antihypertensive agent in children with renal hypertension . It is well tolerated , even in mild renal insufficiency . In addition , the drug has a persistent antiproteinuric action in about half of the patients contributing to conserve renal function Objective . Angiotensin-converting enzyme ( ACE ) inhibitors have been shown to lower central augmentation index ( cAI ) , an index of arterial wave reflection , more than β-blockers . We tested whether this is also true for long-term treatment with an angiotensin receptor blocker ( ARB ) . Methods . One-hundred and fifty-six subjects with essential hypertension were r and omised to treatment with either irbesartan or atenolol .  cAI and central blood pressure ( BP ) were determined by pulse wave analysis from the radial and the carotid artery after six and after 18 months treatment . Results . Peripheral and central systolic and diastolic BP were reduced to a similar extent A in the two groups . cAI was reduced with irbesartan , but increased with atenolol ( derived from the carotid artery : -6±10 vs. -4±12 % after six months , p<0.001 ; —4±12 vs. + 1±11 % after 18 months ; p=0.011 ) . Furthermore , central to peripheral pulse pressure ( PP ) amplification was unaffected by treatment with irbesartan , but decreased with atenolol . Conclusions . Although treatment with irbesartan and atenolol  similarly decreased peripheral and central BP , only treatment with irbesartan had beneficial effects on arterial wave reflection and preserved PP amplification . These haemodynamic effects may at least partly explain the reported differential effects of ARB versus β-blocker treatment on cardiovascular mortality in patients with essential hypertension Objective To compare the efficacy and safety of the angiotensin II antagonist olmesartan medoxomil ( O ) and the ACE inhibitor ramipril ( R ) in elderly patients with essential arterial hypertension . Methods After a 2-week placebo wash-out 1102 treated or untreated elderly hypertensive patients aged 65–89 years ( office sitting diastolic blood pressure , DBP , 90–109 mmHg and /or office sitting systolic blood pressure , SBP , 140–179 mmHg ) were r and omized double-blind to 12-week treatment with O 10 mg or R 2.5 mg once-daily . After the first 2 and 6 weeks doses could be doubled in non-normalized [ blood pressure ( BP ) < 140/90 mmHg for nondiabetic and < 130/80 mmHg for diabetic ) individuals , up to 40 mg for O and 10 mg for R. Office BPs were assessed at r and omization , after 2 , 6 and 12 weeks of treatment , whereas 24-h ambulatory BP was recorded at r and omization and after 12 weeks . Results In the intention-to-treat population ( 542 patients O and 539 R ) after 12 weeks of treatment baseline-adjusted office SBP and DBP reductions were greater ( P < 0.01 ) with O [ 17.8 ( 95 % confidence interval : 16.8/18.9 ) and 9.2 ( 8.6/9.8 ) mmHg ] than with R [ 15.7 ( 14.7/16.8 ) and 7.7 ( 7.1/8.3 ) mmHg ] . BP normalization rate was also greater under O ( 52.6 vs. 46.0 % R , P < 0.05 ) . In the subgroup of patients with valid ambulatory BP recording ( 318 O and 312 R ) the reduction in 24-h average BP was larger ( P < 0.05 ) with O [ SBP : 11.0 ( 12.2/9.9 ) and DBP : 6.5 ( 7.2/5.8 ) mmHg ] than with R [ 9.0 ( 10.2/7.9 ) and 5.4 ( 6.1/4.7 ) mmHg ] . The larger blood pressure reduction obtained with O was particularly evident in the last 6 h from the dosing interval ; a better homogeneity of the 24-h BP control with O was confirmed by higher smoothness indices . The proportion of patients with drug-related adverse events was comparable in the two groups ( 3.6 O vs. 3.6 % R ) , as well as the number of patients discontinuing study drug because of a side effect ( 14 O vs. 19 R ) . Conclusion In elderly patients with essential arterial hypertension O provides an effective , prolonged and well tolerated BP control , representing a useful option among first-line drug treatments of hypertension in this age group The objective of the study was to examine the influence of angiotensin converting enzyme ( ACE ) inhibition on circulatory responses to st and ardized stress tests in primary mild to moderate hypertension . Patients ( n = 28 ) received 5 mg ramipril daily or placebo for 6 weeks in a double-blind crossover design , followed by 6 months of open ramipril treatment . Mental stress ( a 20-min Stroop 's color word conflict test ) and a cold pressor test were performed at the end of each of the three study periods . Noninvasive blood pressure and heart rate were recorded . Ramipril reduced systolic and diastolic blood pressure levels at rest ( from 146+/-3/99+/-3 with placebo to 135+/-4/94+/-3 at 6 weeks , and 136+/-4/91+/-3 mm Hg at 6 months , in the laboratory ) and during mental stress . Resting heart rates were unchanged by ramipril . Ramipril reduced systolic blood pressure and heart rate responses during mental stress ; diastolic blood pressure responses were unchanged . Ramipril reduced cardiac workload ( systolic blood pressure x heart rate ) levels and responses . Treatment effects at 6 months were generally greater than at 6 weeks . During the cold pressor test systolic and diastolic blood pressure levels were lowered by ramipril , but responses were unchanged . Heart rate responses , however , were reduced . Thus , ramipril reduced cardiac workload levels and responses also during the cold pressor test . These findings show that ACE inhibitors can reduce cardiac workload during stressful situations . If confirmed , this would seem to offer an advantage in the treatment of hypertension Persistence on treatment affects the efficacy of antihypertensive treatment . We prospect ively investigated the persistence on therapy and the extent of  blood pressure ( BP ) control  in 347 hypertensive patients ( age 59.4 ± 6 years ) r and omly allocated to a first-line treatment with : angiotensin-converting enzyme ( ACE ) inhibitors , calcium-channel blockers ( CCBs ) , ß-blockers , angiotensin-II receptor blockers ( ARBs ) , or diuretics and followed-up for 24-months . Persistence on treatment was higher in patients treated with ARBs ( 68.5 % ) and ACE inhibitors ( 64.5 % ) vs CCBs ( 51.6 % ; p < 0.05 ) , β-blockers ( 44.8 % , p < 0.05 ) , and diuretics ( 34.4 % , p < 0.01 ) . No ARB , ACE inhibitor , β-blocker , or diuretic was associated with a higher persistence in therapy compared with the other molecules used in each therapeutic class . The rate of persistence was significantly higher in patients treated with lercanidipine vs others CCBs ( 59.3 % vs 46.6 % , p < 0.05 ) . Systolic and diastolic BP was decreased more successfully in patients treated with ARBs ( −11.2/−5.8 mmHg ) , ACE inhibitors ( −10.5/−5.1 mmHg ) , and CCBs ( −8.5/−4.6 mmHg ) compared with ß-blockers ( −4.0/−2.3 mmHg p < 0.05 ) and diuretics ( −2.3/−2.1 mmHg , p < 0.05 ) . No ARB , ACE inhibitor , β-blocker , or diuretic was associated with a higher BP control compared with the other molecules used in each therapeutic class . A trend toward a better BP control was observed in response to lercanidipine vs other CCBs ( p = 0.059 ) . The present results confirm the importance of persistence on treatment for the management of hypertension in clinical practice This multicentre , double-blind , parallel-group , placebo-controlled study compared the antihypertensive effects of equal doses of two long-acting angiotensin converting enzyme ( ACE ) inhibitors . After a two-week , placebo run-in phase , 110 patients with mild to moderate hypertension were r and omised to receive 10 mg lisinopril or enalapril , or placebo for 4 weeks . Office BPs were measured at regular intervals throughout the study . Twenty-four hour ambulatory blood pressure ( ABP ) was measured at baseline and after the first and final doses of study drug . Serum ACE activity and aldosterone were obtained concomitantly with each ABP monitoring . Office BP differences from placebo reached ( P less than 0.05 ) or approached ( P less than 0.10 ) statistical significance at all observations for the lisinopril group but were not significant for any observation in the enalapril group and approached significance on two occasions . After four weeks of treatment , ABP analysis revealed that the lisinopril and enalapril groups , when compared with placebo , had similar and significant systolic and diastolic AUC reductions ( P less than 0.01 ) from baseline over the 24 h dosing interval . During the second half of the dosing interval , 13 - 24 h post drug administration , the lisinopril group was significantly different from placebo ( systolic BP , P = 0.002 ; diastolic BP , P = 0.005 ) while the enalapril group was not . Both drugs were well tolerated . The results indicate that monotherapy with 10 mg of lisinopril is as effective as with 10 mg of enalapril , and that ABP monitoring is useful in more precisely depicting the clinical effect of the known pharmacokinetic properties of these two agents Sibutramine treatment in obesity results in significantly greater weight reduction compared with placebo , although weight loss with sibutramine may be accompanied by small but statistically significant mean increases in blood pressure ( BP ) . This 52-week , placebo-controlled , double-blind , r and omised study investigated the effects of sibutramine 20 mg once daily or placebo on body weight in 220 obese ( body mass index ( BMI ) 27–40 kg/m2 ) , hypertensive patients . At r and omisation , hypertension was well controlled ( ⩽95 mm Hg diastolic blood pressure ( DBP ) ) with an angiotensin-converting enzyme ( ACE ) inhibitor , with or without concomitant thiazide diuretic therapy . Therapy for hypertension continued for the 52 weeks of the study . Sibutramine 20 mg produced significantly greater weight loss compared with placebo : 4.5 kg with sibutramine compared with 0.4 kg with placebo ( last observation carried forward ( LOCF ) ; P ⩽ 0.05 ) . A total of 62 patients ( 42.8 % ) treated with sibutramine lost ⩾5 % of their body weight compared with six patients ( 8.3 % ) treated with placebo ; 19 patients ( 13.1 % ) treated with sibutramine lost ⩾10 % of their body weight compared with two patients ( 2.8 % ) treated with placebo ( LOCF ; P⩽ 0.05 for both comparisons ) . Hypertension remained well controlled for the 52 weeks of the study with both sibutramine and placebo treatment . After 52 weeks , the differences between placebo treatment and sibutramine  treatment for both mean supine systolic blood pressure ( SBP ) and DBP were approximately 3 mm Hg : mean DBP was 82.8 mm Hg with placebo treatment compared with 85.5 mm Hg with sibutramine treatment ( LOCF ; P = 0.004 ) and mean SBP was 130.4 mm Hg with placebo compared with 133.1 mm Hg with sibutramine ( LOCF ; P = 0.0497 ; both comparisons , sibutramine vs placebo ) . The mean increases in SBP and DBP did not appear to change the overall risk category for coronary heart disease end points . Changes in pulse rate at week 52 were a decrease of 0.3 beats per minute ( bpm ) for placebo treatment compared with an increase of 5.7 bpm for sibutramine treatment ( P < 0.001 ) . M and ated withdrawals from the study due to protocol -defined changes in BP were not statistically different between the two treatment groups . Greater favourable changes in lipid profile , serum glucose , and uric acid could be accounted for by greater weight losses occurring in the sibutramine treatment group . Sibutramine was well tolerated . This study indicates that in obese patients whose hypertension is well controlled at the outset with an ACE inhibitor  , with or without concomitant thiazide diuretic therapy  , sibutramine safely and effectively achieves weight loss without compromising good BP control Background : Theoretically , angiotensin II receptor blockers ( ARBs ) have certain advantages over angiotensin-converting enzyme inhibitors , but the contribution of these advantages to the clinical effect of ARBs is not known . Objective : To compare the efficacy and tolerability of telmisartan with enalapril in patients of essential hypertension . Material s and Methods : Patients of mild to moderate hypertension were r and omized to receive either 40 mg of telmisartan or enalapril 10 mg once a day orally for 12 weeks . At each visit , the systolic blood pressure ( BP ) , diastolic BP and heart rate of each patient were recorded . Investigations such as hemogram hemoglobin , total leucocytes count ( Hb , TLC ) , serum creatinine , serum glutamic oxaloacetic transaminase , serum glutamic pyruric transaminase ( SGOT , SGPT ) r and om blood sugar and urine examination were performed at baseline and after 12 weeks of the treatment period . Results : The mean reduction in systolic BP in the telmisartan/enalapril group was 26.38 ± 10.98/26.74 ± 8.24 mmHg while the mean reduction in diastolic BP in the telmisartan/enalapril group was 14 ± 2.98/9.71 ± 4.23 mmHg , respectively , at 12 weeks . When the reduction in systolic BP in the two groups was compared , there was no significant difference between the groups ( P > 0.05 ) . However , the mean reduction in diastolic BP achieved with telmisartan at 12 weeks was significantly higher ( P < 0.001 ) than that achieved with enalapril after the corresponding period . The overall frequency of adverse-effects was similar . However , in the enalapril group , the incidence of dry cough was higher as compared to that in the telmisartan group ( 11.43 % vs. 0 % , respectively ; P < 0.05 ) . Conclusion : Telmisartan produces a greater reduction in diastolic BP than enalapril and is free from the adverse-effect of dry cough that is commonly encountered with enalapril Hypertension Objective treatment based on Measurement by Electrical Devices of Blood Pressure Study ( HOMED BP Study ) is the first large‐scale intervention trial in Japan using a Prospect i ve R and omized Open Blinded Endpoint ( PROBE ) design to determine an optimal target blood pressure ( BP ) level on the basis of self‐measured BP at home , and an optimal initial course of antihypertensive medication . The registered patients are r and omized to either a more intensive BP‐lowering group ( home systolic BP < 125 mmHg and diastolic < 80 mmHg ) or a less intensive group ( home systolic/diastolic BP within the range 134–125/84–80 mmHg ) by host computer via the Internet . The differential effect of three classes of initial antihypertensive regimens on the prognosis , i.e. , calcium antagonist ( Ca‐A ) , angiotensin‐converting enzyme inhibitor ( ACE‐I ) or angiotensin II receptor antagonist ( ARB ) , which are used most frequently in Japan , are examined . Three regimens are also r and omly assigned to the host computer via the Internet . A pilot study was started in May 2001 . In March 2002 , the number of participating doctors was 461 . At the end of March 2002 , 546 patients were recruited . Of these , 412 ( 202 men and 210 women , aged 58.4 ± 10.2 y ) were r and omized . Patients will be recruited until February , 2006 and followed for 7 years Objectives To investigate the relationship between polymorphisms in the angiotensin converting enzyme ( ACE ) , angiotensinogen ( AGT ) and type 1 angiotensin-II ( AT1R ) genes and ( 1 ) quantitative variations in blood pressure and ( 2 ) the blood pressure response to ACE inhibition in a hypertensive cohort . Design and methods We administered monotherapy with ACE inhibitors to 125 previously untreated essential hypertensives . Genotypes for ACE insertion and deletion , AGT M235 T and AT1R A1166±C polymorphisms were determined in DNA extracted from peripheral blood leucocytes . The influence of genotype on pretreatment blood pressure and the ACE inhibitor-induced decrease in blood pressure was tested by analysis of variance and multiple regression analysis , adjusting for age , sex , body mass index , alcohol intake and , where appropriate , pretreatment blood pressure . Results ACE and AT1R genotypes were independent predictors of pretreatment systolic and diastolic blood pressure , with an apparent interaction between these two gene loci . Although it did not influence pretreatment blood pressure in this population , AGT genotype was an independent predictor of the blood pressure response to ACE inhibition . Conclusions The ACE and AT1R gene loci ( chromosomes 17q and 3q , respectively ) may carry alleles influencing blood pressure variation in this hypertensive population , with a possible epistatic interaction between the two loci . The AGT T235 allele does not appear to be a marker for blood pressure variation in this group , but variants on chromosome 1q lying in or near the AGT gene may contribute to individual differences in the blood pressure response to ACE inhibition . Among essential hypertensives , differences in the ACE inhibitor response appear , in part , to be genetically determined The benefit of the add-on angiotensin II receptor blocker c and esartan to angiotensin-converting enzyme ( ACE ) inhibitors in inhibition of progression of nephropathy in hypertensive patient with nondiabetic renal disease compared with monotherapy with ACE inhibitors remains controversial . All patients were previously treated with ACE inhibitors .  Urinary protein excretion of patients exceeded 1.0 g/d despite treatment with ACE inhibitors . Ninety hypertensive patients with chronic renal insufficiency were r and omly assigned to one of two groups . One group received ACE inhibitor plus c and esartan ( 2 to 12 mg/d ) , and a control group received only ACE inhibitor . The target BP was < or = 130/80 mmHg . The primary outcome was the changes in serum creatinine and the reduction of proteinuria . The mean duration of follow-up was 3.1 + /- 0.4 yr . At years 2 and 3 , systolic and diastolic BP were reduced from 140 + /- 3/84 + /- 2 to 129 + /- 1/78 + /- 2 mmHg ( c and esartan group ) and from 135 + /- 2/85 + /- 2 to 130 + /- 2/80 + /- 2 mmHg ( ACE inhibitors group ) . In both groups , both systolic and diastolic BP decreased significantly from the beginning to the end of the study ( P < 0.01 ) . The serum creatinine concentration increased from 3.02 + /- 0.27 to 3.38 + /- 0.49 mg/dl ( c and esartan plus ACE inhibitor group ) versus 3.00 + /- 0.37 to 4.48 + /- 0.57 mg/dl ( ACE inhibitor group ; P < 0.01 ) at year 3 . Although the level of proteinuria significantly declined in each group ( P < 0.05 ) , the degree of reductions in proteinuria was greater in the c and esartan group than in the ACE inhibitors group ( P < 0.01 ) . In the patients who were treated with c and esartan and ACE inhibitor or ACE inhibitor alone , pretreatment proteinuria correlated significantly with decline of renal function , whereas reduction of proteinuria negatively correlated with decline in renal function in the patients who were treated with c and esartan . C and esartan with an ACE inhibitor is effective in slowing the progression of renal insufficiency in hypertensive patients with nondiabetic renal disease through reduction of proteinuria OBJECTIVES Despite a broad and efficient pharmacological antihypertensive armamentarium , blood pressure ( BP ) control is suboptimal and heterogeneous throughout Europe . Recent representative data from Switzerl and are limited . The goal of the present survey was therefore to assess the actual control rate of high BP in Switzerl and in accordance with current guidelines . The influence of risk factors , target organ damage and medication on BP levels and control was also evaluated . METHODS A cross-sectional visit-based survey of ambulatory hypertensive patients was performed in 2009 in Switzerl and . 281 r and omly selected physicians provided data on 5 consecutive hypertensive patients attending their practice s for BP follow-up . Data were anonymously collected on demographics , comorbidities and current medication , and BP was recorded . Subsequent modification of pharmacological antihypertensive therapy was assessed . RESULTS Data from 1376 patients were available . Mean age was 65 ± 12 years , 53.9 % were male subjects . 26.4 % had complicated hypertension . Overall , BP control ( < 140/90 mm Hg for uncomplicated and < 130/80 mm Hg for complicated hypertension ) was achieved in 48.9 % . Compared to patients with complicated hypertension , BP control was better in patients with uncomplicated hypertension ( 59.4 % vs. 19.2 % , p < 0.001 ) . As a monotherapy the most prescribed drug class were angiotensin receptor blockers ( ARB , 41 % ) , followed by angiotensin converting enzyme ( ACE ) inhibitors ( 21.5 % ) , betablockers ( 20.8 % ) and calcium channel blockers ( CCB , 10.8 % ) . The most prescribed drug combinations were ARB + diuretic ( 30.1 % ) and ACE inhibitors + diuretic ( 15.3 % ) . 46 % were receiving a fixed drug combination . In only 32.7 % of patients with uncontrolled hypertension was a change in drug therapy made . CONCLUSION This representative survey on treated adult hypertensive patients shows that , compared to earlier reports , the control rate of hypertension has improved in Switzerl and for uncomplicated but not for complicated , particularly diabetes-associated hypertension . ARBs and ACE inhibitors are the most prescribed antihypertensive drugs for monotherapy , whereas diuretics and ARBs were the most used for combination therapy The concept of initiating treatment of mild-to-moderate hypertension with a low-dose combination of reserpine and the thiazide clopamide in comparison to monotherapy with an ACE inhibitor was investigated . A total of 127 adult out patients with diastolic blood pressure between 100 and 114 mmHg were r and omized into this double-blind , parallel group study . After a 2-week wash-out period and a subsequent 2-week placebo run-in period , they were allocated to once-daily treatment with 0.1 mg reserpine plus 5 mg clopamide ( R/C ) , or 5 mg enalapril . If diastolic blood pressure was not normalized after 3 weeks of therapy ( i.e. DBP < 90 mmHg ) , the dosage was doubled from week 4 to 6 . The primary efficacy variables were the change from baseline in mean sitting diastolic and systolic blood pressure ( DBP/SBP ) after 3 weeks of therapy . Secondary variables included the change in DBP and SBP after 6 weeks of therapy , the BP normalization rates at 3 and 6 weeks and , concerning tolerability , the rates of adverse events after 6 weeks of therapy . An intent-to-treat analysis was performed . The reserpine/ clopamide and enalapril groups did not differ with regard to demographic and baseline characteristics ( mean age 57 or 58 years , respectively ; 63 % or 56 % males , respectively ; mean SBP/DBP after the 2-week placebo period = 156 mmHg/104 mmHg in both groups ) . After 3 weeks of treatment with one capsule daily , mean SBP/DBP reduction from baseline ( 24 h after last medication intake ) in the R/C combination group was -19.6/ -17.0 mmHg , in the enalapril group -6.1/ -9.5 mmHg ( between-group comparison : 2p < 0.01 for both parameters ) . The normalization rates for DBP ( < 90 mmHg ) were 64.1 % ( R/C ) and 28.6 % ( enalapril ) ( 2p < 0.01 ) . Adverse events that were considered possibly or definitely drug-related by the investigator were noted in 11 patients ( 17.2 % ) in the R/C group and in 9 patients ( 14.3 % ) in the enalapril group ( NS ) . Two patients in the enalapril group discontinued the study prematurely due to adverse events ( cough ; skin eruption ) . In the treatment of mild-to-moderate hypertension , a low-dose combination of reserpine and clopamide once a day is considerably more effective than , and as tolerable as , 5 - 10 mg of enalapril once a day . These findings suggest that treatment with a combination of different antihypertensives with different modes of action in low doses is a rational alternative to conventional monotherapy in the first-line treatment of hypertension . Besides , the " old " reserpine-diuretic regimen also in these days appears to be a rational alternative to " modern " monotherapies Background Azilsartan medoxomil ( AZL-M ) , has been demonstrated to be more effective than the other sartans currently in use ; however , there is insufficient information available comparing it with ACE-inhibitors . Therefore , we aim ed to compare the efficacy , safety , and tolerability of AZL-M with that of ACE-inhibitors in a real life clinical setting . Methods The EARLY registry is a prospect i ve , observational , national , multicentre registry with a follow-up period of 12 months . There were two principal objectives : 1 ) documentation of the achievement of target BP values set according to recent national and international guidelines , and 2 ) description of the safety profile of AZL-M. Results A total of 3 849 patients with essential arterial hypertension were recruited from primary care offices in Germany . Patients who initiated monotherapy at baseline comprising either AZL-M or an ACE-inhibitor were included at a ratio of seven to three . Results demonstrated that a blood pressure target of < 140/90 mmHg was achieved by a significantly greater proportion of patients in the AZL-M group ( 61.1 % ) compared with the ACE-inhibitor group ( 56.4 % ; p < 0.05 ; OR , 1.21 ; 95 % CI , 1.03–1.42 ) , with this finding maintained after adjusting for differences in baseline characteristics . AZL-M appeared to have an equivalent safety profile to the ACE-inhibitors , with a similar incidence of adverse events in the two patient groups ( p = 0.73 ) . Conclusions These data add to the results of previous r and omized controlled clinical trials suggesting that , compared with other agents that target the renin – angiotensin system , AZL-M provides statistically significant albeit small improvements in blood pressure control AIM To compare the efficacy of indapamide ( 1.25 mg daily ) and low-salt diet ( < 100 mmol/day ) separately and in combination in essential hypertensive patients with inadequate BP response to perindopril .  DESIGN AND METHODS R and omized double-blind , double-dummy , crossover design . The r and omized treatments were indapamide 1.25 mg daily , sodium chloride 80 mmol daily , the combination of indapamide and sodium chloride and placebo . All patients received perindopril 4 mg daily and maintained a low-sodium diet . RESULTS 19 patients entered and 17 completed the study . Prior to r and omization , average clinic sitting blood pressure was 162/101 mm Hg and average 24-h urine sodium excretion was 157 mmol/day . Compared to the phase in which patients received perindopril with sodium repletion , clinic and ambulatory BPs were significantly reduced ( p<0.01 ) in all the other phases . Indapamide had a greater effect on BP than dietary sodium restriction , and in combination their effects were additive . The effect of indapamide on ambulatory BP persisted throughout 24 h , but the effect of the low-salt diet was predominantly observed during waking hours . CONCLUSIONS In hypertensives with BP resistant to the angiotensin converting enzyme ( ACE ) inhibitor perindopril , the diuretic indapamide had greater additional efficacy and longer duration of action than dietary sodium restriction . In combination they had additive effects on BP Angiotensin-converting enzyme ( ACE ) inhibitors may reduce urinary albumin excretion ( UAE ) by decreasing glomerular pressure and increasing glomerular charge selectivity through preservation of glycosaminoglycans . The effect of Angiotensin II antagonism on glomerular charge selectivity remains to be determined . The aim of this study was to compare the effects of an AT1 blocker losartan and an ACE inhibitor ( ACE-I ) enalapril on UAE , extracellular matrix proteins , glycosaminoglycan excretion ( UGAG ) and red blood cell anionic charge ( RBCCh ) which are the indirect markers of glomerular basement membrane anionic content in hypertensive Type 2 diabetic patients . Twenty-four patients were r and omised into two groups and received either enalapril ( 5—20 mg/d ) or losartan ( 50—100 mg/d ) . All parameters were measured at baseline and after six months of treatment . At the end of six months , systolic and diastolic blood pressures ( BP ) , UAE rates , UGAG excretion and RBCCh were significantly and equally reduced in both treatment groups compared with baseline . RBCCh was negatively correlated with UAE ( r=-0 . O 57 , p<0.0001 ) and UGAG excretion ( r=-0.57 , Rp<0.0001 ) ; UAE was correlated with UGAG excretion ( r=0.58 , p<0.0001 ) . In conclusion , enalapril and losartan treatment were equally effective in reducing BP , UAE as well as UGAG excretion and preserving RBCCh in hypertensive Type 2 diabetic patients . ACE inhibition and AT1-receptor blockade may have favourable effects on preserving glomerular anionic content in hypertensive diabetic patients Hypertensive emergencies , and to a certain extent their treatment , contribute to morbidity and mortality in elderly patients . We studied 22 hospitalized patients , aged 70 - 90 years , all of whom had moderate essential hypertensive . During acute hypertension , mean systolic and diastolic blood pressure rose to 230 + /- 24 and 120 + /- 22 mmHg , respectively . Symptoms of reduced tissue perfusion/oxygenation and /or organ failure occurred , forcing us to begin antihypertensive therapy . We administered 50 mg of the angiotensin converting enzyme ( ACE ) inhibitor captopril sublingually , and within 15 min , systolic blood pressure decreased by an average 60 + /- 16 mmHg and diastolic blood pressure by an average 25 + /- 14 mmHg . There was no significant change in the heart rate . In addition , we treated 22 comparable patients with 10 mg nifedipine sublingually and observed , in four cases , a greater fall in blood pressure ( up to 90 mmHg ) together with tachycardia . These results show the beneficial effects of captopril in the treatment of hypertensive emergencies in elderly patients . The absence of dangerous side effects indicates that ACE inhibitors can be used as first-choice drugs for the treatment of acute hypertensive crises , even in old age The aim of this study was to investigate the relationship between polymorphism of the anglotensin-converting enzyme ( ACE ) gene and the blood pressure response to ACE inhibition in a hypertensive cohort .  Imidapril ( 5 - 10 mg/day ) or benazepril ( 10 - 20 mg/day ) was administered for 6 weeks to 517 essential hypertensives . ACE gene polymorphism was examined by the polymerase chain reaction ( PCR ) method and the patients were classified as having the 190-bp deletion homozygous ( DD ) genotype , the 490-bp insertion homozygous ( II ) genotype , or the 490-bp insertion , 190-bp deletion heterozygous ( ID ) genotype . The achieved change in systolic and diastolic blood pressure ( SBP and DBP ) was analyzed for association with genotypes at the ACE gene locus . The DD genotype was observed in 132 patients ( 25.5 % ) , the ID genotype in 255 patients ( 49.3 % ) , and the II genotype in 130 patients ( 25.2 % ) . The SBP reductions in the patients with the DD genotype , II genotype , and ID genotype were -14.5 + /- 12.7 mmHg , -14.3 + /- 13.1 mmHg and -14.0 + /- 12.2 mmHg , respectively ( p = 0.94 ) . The DBP reductions in the patients with the DD genotype , II genotype , and ID genotype were -8.7 + /- 7.4 mmHg , -8.7 + /- 7.7 mmHg and -8.5 + /- 6.7 mmHg , respectively ( p = 0.96 ) . There was no significant association between the ACE gene polymorphisms and the response to ACE inhibition . These results suggest that ACE genotype does not predict the blood pressure-lowering response to antihypertensive treatment with ACE inhibition OUTCOMES Extensive data from r and omised controlled trials have shown the benefit of treating hypertension . The target blood pressure ( BP ) for antihypertensive management is systolic < 140 mmHg and diastolic < 90 mmHg with minimal or no drug side-effects ; however , stricter BP control is required for patients with end-organ damage , co-existing risk factors and co-morbidity , e.g. diabetes mellitus . The reduction of BP in the elderly and in those with severe hypertension should be achieved gradually over 1 month . Co-existent risk factors should also be controlled . BENEFITS Benefits of management include reduced risks of stroke , cardiac failure , chronic kidney disease and coronary heart disease . RECOMMENDATIONS The correct BP measurement procedure is described , and evaluation of cardiovascular risk factors and recommendations for antihypertensive therapy are stipulated . The total cardiovascular disease risk profile should be determined for all patients to inform management strategies . Lifestyle modification and patient education are cornerstones in the management of every patient . Major indications , pre caution s and contra-indications to each recommended antihypertensive drug are listed . Combination therapy should be considered ab initio if the BP is ≥ 20/10 mmHg . First-line drug therapy for uncomplicated hypertension includes low-dose thiazide-like diuretics , calcium channel blockers ( CCBs ) or angiotensin-converting enzyme inhibitors ( ACE-Is ) ( or ARBs - angiotensin II receptor blockers ) . If the target BP is not obtained , a second antihypertensive should be added from the aforementioned list . If the target BP is still not met , the third remaining antihypertensive agent should be used . In black patients  either thiazide-like diuretics or CCBs can be used initially , because response rates are better than with ACE-Is or β-blockers . In treating resistant hypertension , a central ly acting drug , vasodilator , α-blocker , spironolactone or β-locker should be added . This guideline includes management of specific situations , i.e. hypertensive emergency and urgency , severe hypertension with target organ damage , hypertension in diabetes mellitus , resistant hypertension , fixed drug combinations , new trials in hypertension , and interactions of antihypertensive agents with other drugs . VALIDITY The guideline was developed by the Southern African Hypertension Society The effects of the ACE inhibitor spirapril and of hydrochlorothiazide on left ventricular diastolic function were studied . Thirteen patients with mild to moderate essential hypertension completed this r and omized , double-blinded , placebo-controlled , crossover study . After a three-week run-in period the patients entered three periods lasting four weeks each , wherein they were treated with placebo , spirapril , or hydrochlorothiazide .  Blood pressure , hemodynamic variables ( stroke volume , heart rate , cardiac output , index of contractility , and systemic vascular resistance ) , echocardiography ( left ventricular mass ) , and Doppler-derived atrial to early (A/E)-ratio velocity time integrals ( VTI ) were measured at the end of each of the four periods . Spirapril lowered the A/E-ratio VTIs ( 0.57 , 0.12 - 1.00 ) ( P < 0.02 ) as compared with both placebo ( 0.80 , 0.50 - 2.67 ) and hydrochlorothiazide ( 0.83 , 0.44 - 1.25 ) , and the drug normalized the A/E-ratio VTI in those patients with elevated values . The hemodynamic variables , left ventricular mass , and end-systolic wall stress were unchanged during all three treatments . There were no significant changes in mean blood pressure during the treatment periods . These results indicate that spirapril lowers A/E ratio within four weeks in patients with mild to moderate essential hypertension . It thereby seems able to improve left ventricular diastolic function . The effect is not dependent upon changes in hemodynamic variables , blood pressure , left ventricular mass , or end-systolic wall stress BACKGROUND Previous reports have demonstrated the antihypertensive efficacy of high doses of spironolactone in subjects with primary aldosteronism and , to a lesser degree , subjects with resistant hypertension . METHODS In current analysis , we examined the antihypertensive benefit of adding low-dose spironolactone to multidrug regimens that included a diuretic and an angiotensin-converting enzyme ( ACE ) inhibitor or angiotensin receptor blocker ( ARB ) in subjects with resistant hypertension with and without primary aldosteronism . Subjects referred for resistant hypertension were evaluated with an early morning plasma renin activity , 24-h urinary aldosterone and sodium during a high dietary salt ingestion . The diagnosis of primary aldosteronism was confirmed with a renin activity < 1.0 ng/mL/h , urinary aldosterone > 12 mug/24 h and urinary sodium > 200 mEq/24 h. After biochemical evaluation , spironolactone ( 12.5 to 25 mg/d ) was added to each subject 's antihypertensive regimen . If blood pressure ( BP ) remained uncontrolled , the dose of spironolactone was titrated up to 50 mg/d . Follow-up BP was determined at 6 weeks , 3 months , and 6 months . RESULTS A total number of 76 subjects were included in the analysis , 34 of whom had biochemical primary aldosteronism . Low-dose spironolactone was associated with an additional mean decrease in BP of 21 + /- 21/10 + /- 14 mm Hg at 6 weeks and 25 + /- 20/12 + /- 12 mm Hg at 6-month follow-up . The BP reduction was similar in subjects with and without primary aldosteronism and was additive to the use of ACE inhibitors , ARBs , and diuretics . CONCLUSIONS We conclude that low-dose spironolactone provides significant additive BP reduction in African American and white subjects with resistant hypertension with and without primary aldosteronism Co-administration of antihypertensive drug therapy and hormonal replacement therapy ( HRT ) is frequent in postmenopausal women but it is not known whether HRT interacts with concomitant antihypertensive therapy . The present study was design ed to investigate efficacy and safety of the ACE inhibitor moexipril in comparison to placebo in hypertensive , postmenopausal women on HRT . After a 4-week placebo run-in phase , 95 postmenopausal women ( 35–74 years of age ) who had a sitting diastolic blood pressure ( BP ) of 95–114 mm Hg and were treated with HRT were r and omised to a 12-week treatment with moexipril 15 mg or placebo .  Efficacy and safety were assessed by measuring changes in sitting BP and metabolic parameters associated with cardiovascular disease including triglycerides , total cholesterol , HDL , LDL , total cholesterol/HDL ratio and glucose . Adverse events were recorded continuously . After 12 weeks of treatment , moexipril 15 mg was significantly more effective in reducing sitting systolic and diastolic BP from baseline than placebo ( −12.2/ −9.9 mm Hg vs −1.6/−4.3 mm Hg , P < 0.001 ) . metabolic parameters were not affected by treatment with moexipril  : mean levels of triglycerides , total cholesterol , hdl , ldl , total cholesterol/hdl ratio and glucose remained unchanged throughout the study . fibrinogen , an independent cardiovascular risk factor , increased after placebo ( + 35.0 mg/dl ) and decreased after treatment with moexipril ( −33.6 mg/dl ) , the difference , however , was not statistically significant .  moexipril  was well-tolerated by postmenopausal women using hrt . the most frequent adverse events included headache ( 21.3 % ) , cough ( 12.8 % ) and rhinitis ( 10.6 % ) and there were no significant differences in the number and severity of adverse events between the moexipril and placebo groups . this study indicates that moexipril is effective and well tolerated in the treatment of hypertensive , postmenopausal women and can safely be co-administered to hrt Objectives . To evaluate the efficacy , safety and tolerability of aliskiren in elderly patients ( ⩾65 years old ) with essential hypertension . Methods . In this double‐blind , multicenter study , 355 elderly patients with hypertension [ office mean sitting systolic blood pressure ( msSBP ) ⩾145–<180 mmHg and mean 24‐h ambulatory systolic BP ( ASBP ) ⩾135 mmHg ] were r and omized to once‐daily treatment for 8 weeks with aliskiren 75 mg ( n = 91 ) , 150 mg ( n = 84 ) , 300 mg ( n = 94 ) or the comparator lisinopril 10 mg ( n = 86 ) . The primary efficacy variable was change in mean 24‐h ASBP . Results . At endpoint , aliskiren 75 mg , 150 mg , 300 mg and lisinopril 10 mg lowered mean 24‐h ASBP ( least‐squares mean±SEM ) by 8.4±0.8 , 7.1±0.8 , 8.7±0.8 and 10.2±0.9 mmHg , and mean 24‐h ambulatory diastolic BP by 4.5±0.5 , 3.6±0.5 , 3.9±0.5 and 6.3±0.5 mmHg , respectively , with no significant difference between aliskiren doses . The trough‐to‐peak ratio for ASBP reduction with aliskiren 75 mg , 150 mg , 300 mg and lisinopril 10 mg was 0.77 , 0.64 , 0.79 and 0.87 , respectively . All treatments lowered office msSBP and mean sitting diastolic BP ( msDBP ) compared with baseline . A significantly greater proportion of patients receiving aliskiren 300 mg achieved BP control ( msSBP/msDBP < 140/90 mmHg ) compared with those receiving aliskiren 75 mg ( 36.2 % vs 24.2 % , p = 0.033 ) . There was no evidence of dose‐related increases in the rate of adverse events with aliskiren treatment . Conclusions . Aliskiren , a novel direct renin inhibitor , provides effective 24‐h BP lowering with no evidence of dose‐related increases in the incidence of adverse events in elderly patients with hypertension . Trial registration : Clinical Trials.gov identifier : NCT00219167 To investigate the concept of initiating therapy with low doses of a calcium antagonist and an ACE inhibitor , a fixed combination of isradipine 2.5 mg plus the ACE inhibitor spirapril 3 mg was compared with its components , with the full-dose monotherapies ( isradipine 5 mg or spirapril 6 mg ) , and with placebo . After a 2-week wash out phase in pretreated patients and a subsequent 2-week placebo period , 405 patients with a diastolic blood pressure ( DBP ) between 100 and 114 mmHg were r and omly allocated to 12-week once-daily double-blind treatment in one of the six treatment arms . In patients whose blood pressure was not normalized ( defined as DBP≤90 mmHg ) after 6 weeks of treatment , the dosage of either medication was doubled or , in the placebo group , was switched to the fixed combination . After week 6 , the mean reductions from baseline in sitting systolic/diastolic blood pressure 24 hours after dosing ( trough ) for the fixed combination or the monotherapies isradipine 5 mg , isradipine 2.5 mg , spirapril 6 mg , spirapril 3 mg , and placebo were10.4/8.7 , 10.0/9.4 , 6.5/6.7 , 10.0/8.3 , 7.0/5.8 , and 2.2/4.7 mmHg , respectively . The blood pressure changes obtained with the low-dose fixed combination were essentially identical to those observed with the full-dose monotherapies , thus showing an additive effect of low-dose isradipine and spirapril . In terms of tolerability , the lowest rate of any adverse events was found in the combination group . In this group , typical adverse events of calcium antagonists , such as headache , flushing , ankle edema , or palpitations , were observed only in 5 % , 2 % , 1 % , and 0 % , respectively , dry cough , considered typical for ACE inhibitors , was observed in only 1 % of the combination group . In conclusion , the low-dose components isradipine 2.5 mg and spirapril 3 mg were shown to have an additive effect when combined , exerting a blood pressure – lowering effect comparable with the full doses and a trend to a better tolerability profile in comparison with the st and ard doses . Thus , low-dose combination therapy with these drugs appears to be a rational alternative to conventional monotherapy in the first-line treatment of hypertension Summary The antihypertensive efficacy both of angiotensin converting enzyme ( ACE ) inhibitors and thiazide diuretics has been cl aim ed to be influenced by plasma renin activity , which declines with age and is low in blacks . In a double-blind , placebo-controlled , double-dummy , r and omized , parallel-group preliminary study , the antihypertensive efficacy and tolerability of the ACE inhibitor enalapril ( 20 mg day−1 ) and hydrochlorothiazide ( 50 mg day−1 ) were evaluated and compared for 4 weeks in 20 African patients with essential hypertension . The two groups had similar baseline clinical features and serum Na+ and K+ levels .  Hydrochlorothiazide caused a significant and sustained fall in erect blood pressure with a reflex tachycardia .  Enalapril exerted only a modest antihypertensive action , but significantly reduced erect heart rate . Direct comparison of hydrochlorothiazide — and enalapril — induced hypotension suggested a greater fall in subjects on the thiazide . The 95 % confidence limits for the thiazide-enalapril difference in antihypertensive action at the end of the study was 39.5 to −7.5 mm Hg systolic and 22.0 to −6.6 mm Hg diastolic . The maximal blood pressure fall after hydrochlorothiazide was positively correlated with age ( r=0.50;p<0.05 ) , whilst that of enalapril was inversely related age to (r=−0.57,p<0.05).The results are compatible with the notion that ACE inhibitor monotherapy may be less effective than thiazide diuretic treatment in African and black patients with essential hypertension . The findings also support the concept that age and racial factors may influence the response to antihypertensive treatment 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 CONTEXT Hyperuricemia is a predictor for the development of hypertension and is commonly present in new-onset essential hypertension . Experimentally increasing uric acid levels using a uricase inhibitor causes systemic hypertension in animal models . OBJECTIVE To determine whether lowering uric acid lowers blood pressure ( BP ) in hyperuricemic adolescents with newly diagnosed hypertension . DESIGN , SETTING , AND PATIENTS R and omized , double-blind , placebo-controlled , crossover trial ( September 2004-March 2007 ) involving 30 adolescents ( aged 11 - 17 years ) who had newly diagnosed , never-treated stage 1 essential hypertension and serum uric acid levels > or = 6 mg/dL. Participants were treated at the Pediatric Hypertension Clinic at Texas Children 's Hospital in Houston . Patients were excluded if they had stage 2 hypertension or known renal , cardiovascular , gastrointestinal tract , hepatic , or endocrine disease . INTERVENTION Allopurinol , 200 mg twice daily for 4 weeks , and placebo , twice daily for 4 weeks , with a 2-week washout period between treatments . The order of the treatments was r and omized . MAIN OUTCOME MEASURES Change in casual and ambulatory blood pressure . RESULTS For casual BP , the mean change in systolic BP for allopurinol was -6.9 mm Hg ( 95 % confidence interval [ CI ] , -4.5 to -9.3 mm Hg ) vs -2.0 mm Hg ( 95 % CI , 0.3 to -4.3 mm Hg ; P = .009 ) for placebo , and the mean change in diastolic BP for allopurinol was -5.1 mm Hg ( 95 % CI , -2.5 to -7.8 mm Hg ) vs -2.4 ( 95 % CI , 0.2 to -4.1 ; P = .05 ) for placebo . Mean change in mean 24-hour ambulatory systolic BP for allopurinol was -6.3 mm Hg ( 95 % CI , -3.8 to -8.9 mm Hg ) vs 0.8 mm Hg ( 95 % CI , 3.4 to -2.9 mm Hg ; P = .001 ) for placebo and mean 24-hour ambulatory diastolic BP for allopurinol was -4.6 mm Hg ( -2.4 to -6.8 mm Hg ) vs -0.3 mm Hg ( 95 % CI , 2.3 to -2.1 mm Hg ; P = .004 ) for placebo . Twenty of the 30 participants achieved normal BP by casual and ambulatory criteria while taking allopurinol vs 1 participant while taking placebo ( P < .001 ) . CONCLUSIONS In this short-term , crossover study of adolescents with newly diagnosed hypertension , treatment with allopurinol result ed in reduction of BP . The results represent a new potential therapeutic approach , although not a fully developed therapeutic strategy due to potential adverse effects . These preliminary findings require confirmation in larger clinical trials . TRIAL REGISTRATION clinical trials.gov Identifier : NCT00288184 1 . We describe an approach involving a smaller , shorter study , leading onto a longer , larger study in which the antihypertensive effects of ascending doses of imidapril , a new ACE inhibitor , were investigated . Both studies were planned prospect ively , assuming a clinical ly useful fall in BP to be 8 mm Hg ( s.d . = 9 ) . The studies included patients with mild to moderate essential hypertension ( baseline sitting diastolic blood pressure ( SDBP ) 95 - 115 mm Hg ) . After a placebo run-in of 2 - 3 weeks patients received either placebo or imidapril 2.5 , 5 , 10 or 20 mg in the 2 week study ( n = 91 ) or imidapril 5 , 10 , 20 or 40 mg in the 4 week study ( n = 162 ) . 2 . The overall mean baseline SDBP was 103.4 mm Hg ( s.d . 0.62 ) in the initial study and 101.5 mm Hg ( s.d . 0.41 ) in the 4 week study . 3 . Compared with placebo , imidapril 10 , 20 and 40 mg significantly reduced SDBP . There was no significant difference between these doses , suggesting that 10 mg achieved maximal ACE inhibition in most patients . The 2.5 mg dose showed no significant effect . The 5 mg dose gave an intermediate effect . In both studies the overall incidence of adverse events was similar in the imidapril and placebo groups , and was not worrying The effect of various antihypertensive medications on platelet function is of increasing interest . Conflicting effects of captopril on platelet function are reported and the impact of angiotensin converting enzyme ( ACE ) inhibitors not containing a sulfhydryl group such as enalapril , lisinopril , and quinapril on platelet function remains unstudied . Therefore , the aim of the present study was to examine the effect of antihypertensive treatment with quinapril , a novel ACE inhibitor not containing a sulfhydryl group , on platelet function . Ten white men ( age range of 32–61 years ) with untreated mild-to-moderate essential hypertension ( supine diastolic blood pressure > 95 mm Hg ) were treated with 4 weeks each of placebo and quinapril in a double-blind , r and omized , crossover design . Quinapril ( 20 mg twice a day ) significantly lowered systolic ( p < 0.01 ) and diastolic blood pressure ( p < 0.01 ) without any significant effect on heart rate or plasma catecholamines . No significant change was noted for in vitro platelet aggregation induced by epinephrine , ADP , or collagen . Plasma concentrations of the platelet release factors β-thromboglobulin and platelet factor 4 did not change , nor did the platelet content of norepinephrine , platelet weight ( mg/10 ml of blood ) , circulating platelet count , or platelet size . Thus , as assessed by a broad spectrum of platelet parameters , we found that antihypertensive treatment with quinapril has no significant effect on platelet function in patients with mild-to-moderate essential hypertension . These “ platelet-neutral ” properties of quinapril suggest that quinaparil , both from a thromboembolic and a hemostatic point of view , may be a rather safe agent for treatment of hypertension Objectives . This multicenter , three‐armed , open‐labeled study investigated patient compliance of patients receiving irbesartan , angiotensin‐converting enzyme ( ACE ) inhibitors or calcium‐channel blockers ( CCB ) for essential hypertension for a 6‐month period . Patients were either newly diagnosed or switched from existing antihypertensive medication due to lack of efficacy or side‐effects . Methods . Patients were started monotherapy with irbesartan ( n = 377 ) , ACE inhibitors ( n = 298 ) or CCB ( n = 308 ) and were reevaluated on 1st , 3rd , and 6th months of the treatment . The primary endpoint was patient compliance , assessed by proportion of patients who had taken their study medication every day . Efficacy was recorded as mean reductions in blood pressure and the proportion of patients whose blood pressure normalized . Tolerability was assessed by reported adverse events . Results . Significantly more patients receiving irbesartan had complied with study medication after 3 and 6 months of treatment than ACE inhibitors or CCB . Significantly fewer patients receiving irbesartan needed to change their antihypertensive medication . All three study treatments exhibited similar efficacy profiles , but irbesartan had significantly less adverse events . Conclusions . This study demonstrated that patient compliance to irbesartan was significantly superior to other study treatments . Irbesartan is therefore a suitable first‐line therapy for essential hypertension in everyday clinical practice Introduction . Aliskiren is the first in a new class of direct renin inhibitors to be approved for the treatment of hypertension . Patients and methods . In this double-blind , multicentre trial , 694 patients with hypertension ( mean sitting diastolic blood pressure [ BP ] ≥ 95 and < 110 mmHg ) were r and omised to once-daily aliskiren 150 mg ( n=231 ) , atenolol 50 mg ( n=231 ) or the combination ( 150/50 mg ; n=232 ) for six weeks , followed by a further six weeks on double the initial doses of aliskiren and atenolol . Efficacy ( reduction from baseline in mean sitting systolic and diastolic BP ) and tolerability of study treatments were assessed ; plasma renin activity ( PRA ) was measured in a subset of patients . Results . At Week 12 endpoint , aliskiren , atenolol and aliskiren/atenolol  lowered systolic and diastolic BP from baseline by 14.3/11.3 , 14.3/13.7 and 17.3/14.1 mmHg , respectively . Systolic BP reductions with aliskiren/atenolol were significantly greater than those with aliskiren ( p=0.039 ) or atenolol ( p=0.034 ) alone , and diastolic BP reductions were greater than with aliskiren alone ( p<0.001 ) . Diastolic BP changes were larger with atenolol than with aliskiren ( p=0.003 , correlating with the large reductions in pulse rate ( > 10 bpm ) observed with atenolol . Aliskiren , atenolol and aliskiren/atenolol  reduced geometric mean PRA from baseline by 65 % , 52 % and 61 % , respectively . In patients with moderate or high baseline PRA ( ≥ 0.65 ng/ml/hour ) , PRA was reduced to low levels ( < 0.65 ng/ml/hour ) at Week 12 endpoint in a greater proportion of patients receiving aliskiren ( 11/15 patients , 73.3 % ) or aliskiren/atenolol ( 18/23 , 78.3 % ) than with atenolol ( 10/21 , 47.6 % ) . Aliskiren treatment was associated with numerically lower rates of adverse events and discontinuations due to adverse events  compared with atenolol or combination treatment , and unlike atenolol was not associated with bradycardia . Conclusions . Direct renin inhibition with aliskiren may be an appropriate substitute for beta-blocker treatment in patients with uncomplicated hypertension .  Aliskiren also represents an attractive option for dual therapy with atenolol to improve systolic BP/pulse pressure reductions and BP control with maintained tolerability compared with atenolol alone This multicenter , placebo-controlled , double-blind trial of factorial design evaluated the safety and efficacy of combination treatment with the angiotensin-converting enzyme inhibitor , enalapril , and the vascular selective calcium antagonist felodipine extended release ( ER ) in patients with essential hypertension . After a 4-week , single-blind placebo baseline period , 707 patients with sitting diastolic blood pressures ( BPs ) in the range of 95 to 115 mm Hg received placebo , enalapril ( 5 or 20 mg ) , felodipine ER ( 2.5 , 5 , or 10 mg ) , or their combinations for an 8-week double-blind treatment period . All doses of enalapril and felodipine ER had a statistically significant ( p < 0.05 ) additive effect in reducing both systolic and diastolic BP . The trough to peak ratios for the combinations ranged from 0.63 ( enalapril 5 mg-felodipine ER 2.5 mg ) to 0.79 ( enalapril 20 mg-felodipine ER 10 mg ) and were consistent with effective BP control with 1 dose/day . Patients aged > or = 65 years demonstrated a greater reduction in diastolic BP . Combinations of enalapril-felodipine ER were associated with less drug-induced peripheral edema ( 4.1 % ) compared to felodipine ER monotherapy ( 10.8 % ) . There were no serious drug-related adverse effects observed during the study . In this trial , the combination of enalapril and felodipine ER effectively lowered BP and was generally well tolerated with an excellent safety profile when used in the treatment of hypertension OBJECTIVES The primary objective of this study was to investigate the effects of the angiotensin-converting enzyme ( ACE ) inhibitor , ramipril , on carotid atherosclerosis in patients with coronary , cerebrovascular or peripheral vascular disease . BACKGROUND Angiotensin-converting enzyme inhibitors have been shown to reduce the risk of coronary events in various patient groups and to prevent the development of atherosclerosis in animal models . It has been hypothesized that the clinical benefits of ACE inhibitors may , therefore , be mediated by effects on atherosclerosis . METHODS Six hundred seventeen patients were r and omized in equal proportions to ramipril ( 5 - 10 mg daily ) or placebo . At baseline , two years and four years , carotid atherosclerosis was assessed by B-mode ultrasound , and left ventricular mass was assessed by M-mode echocardiography . RESULTS Blood pressure ( BP ) was reduced by a mean of 6 mm Hg systolic and 4 mm Hg diastolic in the ramipril group compared with the placebo group ( p<0.001 ) . There was no difference between groups in the changes in common carotid artery wall thickness ( p = 0.58 ) or in carotid plaque ( p = 0.93 ) . Left ventricular mass index decreased by 3.8 g/m2 ( 4 % ) in the ramipril group compared with the placebo group ( 2p = 0.04 ) . CONCLUSIONS The results provide no support for the hypothesis that reduced atherosclerosis is responsible for the beneficial effects of ACE inhibitors on major coronary events . It is more likely that the benefits are due to lower BP , reduced left ventricular mass or other factors such as reversal of endothelial dysfunction OBJECTIVE A double-blind , placebo-controlled multicenter study involving 34 centers from different Brazilian regions was performed to evaluate the antihypertensive efficacy and tolerability of tr and olapril , an angiotensin I converting enzyme inhibitor , in the treatment of mild-to-moderate systemic arterial hypertension . METHODS Of 262 patients enrolled in this study , 127 were treated with tr and olapril 2 mg/day for 8 consecutive weeks , and the remaining 135 patients received placebo  for the same period of time . Reduction in blood pressure ( BP ) and the occurrence of adverse events during this period were evaluated in both groups . RESULTS Significantly reductions in both systolic and diastolic pressures were observed in patients treated with tr and olapril when compared with those on placebo .  Antihypertensive efficacy was achieved in 57.5 % of the patients on tr and olapril and in 42 % of these normal values of BP were obtained . The efficacy of tr and olapril was similar in all centers , regardless of the area of the country . In a subset of 30 patients who underwent ABPM , responders showed a significant hypotensive effect to tr and olapril throughout the 24 hour day . The adverse event profile was similar in both tr and olapril and placebo groups . CONCLUSION Our results demonstrate , for the first time in a large group of hypertensive patients from different regions in Brazil , good efficacy and tolerability of tr and o-lapril during treatment of mild-to-moderate essential systemic hypertension Central aortic systolic blood pressure ( BP ) is an important determinant of cardiac workload and cardiac hypertrophy . The relationship of central aortic systolic BP and brachial BP varies depending on the stiffness of blood vessels . It is not certain whether the different drug classes affect the brachial and aortic systolic BP in a similar manner . In a double-blind crossover study , we measured the effects of the four major drug classes compared with placebo on central aortic pressure . Central aortic pressure and various indices were determined using the Sphygmo Cor apparatus . The study was undertaken in patients aged 65 to 85 years with systolic BP > 150 mm Hg at study entry . Results are reported for 32 patients who had satisfactory applanation tonometry in all five periods .  Calcium channel blockers and diuretics caused a greater fall in brachial artery systolic BP than angiotensin-converting enzyme ( ACE ) inhibitors or beta-blocking drugs . On placebo , central aorta augmentation pressure and index were 23 mm Hg and 33.3 % ; on ACE inhibitors the values were 18 mm Hg and 30 % ; on beta-blockers , 26 mm Hg and 38.5 % ; on calcium channel blockers , 16 mm Hg and 28 % ; and on diuretics , 17 mm Hg and 28.8 % . The augmentation pressure on beta-blocking drugs was greater than on the other three drug classes ( P < .05 ) , and augmentation pressures on ACE inhibitors , calcium channel blockers , and diuretics were less than on placebo ( P < .05 ) . The lowest central aortic pressures were achieved with calcium blocking drugs and diuretics . Therapy based on brachial artery recordings may thus overestimate the effect of beta-blocking drugs on central aortic systolic BP and underestimate the effectiveness of ACE inhibitors and calcium blocking drugs . The clinical importance of this discrepancy needs to be evaluated BACKGROUND The renoprotective effect of ACE inhibition in chronic renal disease is well established but the studies on effects of calcium antagonists on progression of renal disease and on proteinuria have given varying results . METHODS We conducted an open long-term r and omized prospect i ve multi-centre study comparing the combination of ramipril and felodipine ER ( F ) with either drug alone in non-diabetic renal disease . Included were patients with uncontrolled hypertension ( diastolic blood pressure ( DBP ) ) > or = 95 mmHg on treatment with a diuretic and a beta-blocker . Fifty-one patients received the combination of R and F , 54 patients R , and 53 patients F. The treatment goal was a DBP < 90 mmHg and a similar BP reduction in the three groups . Mean doses at the last visit were 5 + 5 , 10 and 9 mg , respectively , after a mean treatment time of nearly 2 years . The progression of renal impairment was studied by serial measurements of serum creatinine , iohexol clearance , and albuminuria . RESULTS The reduction in supine systolic ( S ) BP and DBP expressed as median values were -19.0/-14.5,-14.3/-15.0 and -13.5/-13.3 mmHg in the R+F , R , and F groups , respectively . There was no significant difference between the groups . When correction for the acute drug effect was performed the R+F group had a slower progression rate of the renal disease ( loss of glomerular filtration rate ( GFR ) ml/min/year ) compared with the F group ( P<0.05 ) but not to the R group ( P>0.20 ) . There was a rise in albuminuria after 2 years in the F group ( P<0.05 ) , but no significant change was found in the other groups . CONCLUSIONS In patients with non-diabetic renal disease the combination of an ACE inhibitor and a calcium antagonist in reduced doses used in addition to baseline therapy with beta-blockers and diuretics , tended to cause a better BP reduction as each drug per se . The R+F treatment also caused a slower progression of the renal disease compared with F alone . The combination treatment seems to afford better BP control and appears to be a favourable therapeutic option in patients with renal disease and hypertension BACKGROUND Few studies have examined to what extent genes might modulate the changes of systolic and diastolic blood pressure ( BP ) with age although , in older population s , systolic BP and diastolic BP vary with age in opposite directions . METHODS This study involved 205 men and 99 women with either systolic-diastolic or isolated systolic hypertension . Age was > 50 years . Using polymerase chain reaction , four gene polymorphisms related to the renin-angiotensin system were independently investigated in men and women . Adjustments to cardiovascular and renal risk factors as well to the sodium/potassium extracellular space ratio were performed . RESULTS Regarding the angiotensin-converting enzyme ( ACE ) gene polymorphism , in men > 50 years of age , the slope ( mm Hg per unit of age ) of the age-diastolic BP ( and not age-systolic BP ) relationships significantly ( P = .0092 ) differed between genotypes : - 0.79 + /- 0.15 ( P < .0001 ) for the DD genotype , -0.53 + /- 0.10 for the ID genotype ( P < .0001 ) , and -0.23 + /- 0.11 for II genotypes ( P = NS ) . Such findings were not observed in the female population in which the age-diastolic BP curves were substantially flatter than in men . No comparable results were observed for gene polymorphisms related either to angiotensinogen or to angiotensin II type 1 receptor . CONCLUSIONS In men > 50 years of age , the ACE gene polymorphism modulates the physiologic age-induced reduction of diastolic BP . The D allele might contribute to enhance this reduction , a finding that needs confirmation using prospect i ve studies Angiotensin-converting enzyme inhibitors and calcium antagonists are 2 classes of antihypertensive agents frequently used either as monotherapy or in combination . A 6-week , multicenter , r and omized , double-blind , placebo-controlled trial was conducted in essential hypertensive patients ( diastolic blood pressures [ BP ] when seated , 95 - 115 mm Hg ) to evaluate the efficacy , dose response , and safety profiles of enalapril combined with a new once-daily formulation of diltiazem .  BP and heart rate were measured at 5 ( peak ) and 24 ( trough ) hours after dose to assess the efficacy and pharmacodynamic profile of the combination given once daily . There were 336 patients r and omly assigned to either enalapril 5 mg plus 1 of 4 dose levels of diltiazem ER ( 60 , 120 , 180 , or 240 mg ) , enalapril 5 mg alone , or placebo . Each combination dose level produced statistically significant reductions ( p < 0.05 ) in trough diastolic BP when seated , compared with placebo ( -6.8 , -8.3 , -10.1 , and -10.3 mm Hg for the diltiazem ER doses of 60 , 120 , 180 , and 240 mg , respectively ) . The 3 highest combination dose levels result ed in statistically significant ( p < 0.05 ) decreases in trough diastolic BP when seated , compared with placebo . There was a significant ( p < 0.001 ) linear dose-response relation . A trough-to-peak ratio > or = 0.5 was shown for the 3 highest combination doses . Drug-related adverse events were seen in 8.9 % to 19 % of the combination patients , 14.3 % of the enalapril patients , and 8.6 % of the placebo patients . The frequency and type of adverse events were those currently noted with each drug studied when used as monotherapy Patients aged 60 years and older with essential hypertension were treated with an angiotensin-converting enzyme inhibitor ( ACE-I ) , delapril ( Adecut ) or a long-acting calcium (Ca)-antagonist , manidipine ( Calslot ) for 3 years . The incidences of cardiovascular events as well as drug-related side effects were compared between the two groups to investigate whether both classes of antihypertensive drugs are beneficial in elderly hypertensive patients . There were no significant differences in characteristics of patients between the two intervention groups , except for slightly lower blood pressure ( P = .08 ) in the Ca-antagonist group at the initiation of the study . There were no significant differences in total death between the two groups . Cardiovascular events ( both fatal and nonfatal ) were noted in 34 of 699 patients ( 22.5/1000 patient-years ) in the ACE-I group and 50 of 1049 patients ( 19.7/1000 patient-years ) in the Ca-antagonist group , with no significant difference found between the two groups . The correlation between cardiovascular incidence and the blood pressure attained during treatment showed a J-shaped phenomenon and suggests that an excessive reduction less than 120 mm Hg in systolic blood pressure ( SBP ) is unnecessary and may be harmful in certain cases . Side effects were more frequent in the ACE-I group than in the Ca-antagonist group ( P = .01 ) . Cough was the major adverse event , occurring in 5.0 % of patients in the ACE-I group . In conclusion , the study indicates that both ACE-I ( delapril ) and Ca-antagonist ( manidipine ) were equally beneficial for reducing cardiovascular morbidity and mortality in elderly hypertensive patients . However , tolerability of ACE-I was lower due to the adverse event of coughing BACKGROUND While the antihypertensive and renoprotective potency of angiotensin-converting enzyme ( ACE ) inhibitors is well-established in adults with hypertension and /or chronic renal failure , little experience exists in pediatric chronic kidney disease . METHODS As part of a prospect i ve assessment of the renoprotective efficacy of ACE inhibition and intensified blood pressure ( BP ) control , 397 children ( ages 3 to 18 years ) with chronic renal failure [ CRF ; glomerular filtration rate ( GFR ) 11 to 80 mL/min/1.73 m2 ] and elevated or high-normal BP received ramipril ( 6 mg/m2 ) following a 6-month run-in period including a two-month washout of any previous ACE inhibitors .  Drug efficacy was assessed by two monthly office BP and proteinuria assessment s , and by ambulatory BP monitoring at start and after 6 months of treatment . RESULTS In the 352 patients completing six months of treatment , 24-hour mean arterial pressure ( MAP ) had decreased by a mean of 11.5 mm Hg ( -2.2 SDS ) in initially hypertensive subjects , but only by 4.4 mm Hg ( -0.8 SDS ) in patients with initially normal BP . A linear correlation was found between MAP at baseline and the change of MAP during treatment ( r= 0.51 ; P < 0.0001 ) . The antihypertensive response was independent of changes in concomitant antihypertensive medication or underlying renal disease . BP was reduced with equal efficacy during day- and nighttime . Urinary protein excretion was reduced by 50 % on average , with similar relative efficacy in patients with hypo/dysplastic nephropathies and glomerulopathies . The magnitude of proteinuria reduction depended on baseline proteinuria ( r= 0.32 , P < 0.0001 ) , and was correlated with the antihypertensive efficacy of the drug ( r= 0.22 , P < 0.001 ) . The incidence of rapid rises in serum creatinine and progression to end-stage CRF during treatment did not differ from the pretreatment observation period . Mean serum potassium increased by 0.3 mmol/L. Ramipril was discontinued in three patients due to symptomatic hypotension or hyperkalemia . Hemoglobin levels decreased by 0.6 g/dL in the first two treatment months and remained stable thereafter . CONCLUSION Ramipril appears to be an effective and safe antihypertensive and antiproteinuric agent in children with CRF-associated hypertension . The BP lowering and antiproteinuric effects are greatest in severely hypertensive and proteinuric children Although blacks have lower plasma renin activity compared to whites , the corresponding differences in serum angiotensin converting enzyme ( ACE ) levels have not been well studied . Furthermore , few studies have examined the relationship of renin activity and ACE levels to blood pressure ( BP ) in blacks . We addressed these questions in a cross-sectional study conducted in 110 blacks and 183 whites who were not on antihypertensive medications . Three BP readings were obtained during a clinic visit . Plasma renin activity was assayed by radioimmunoassay and  serum ACE levels were measured by spectrophotometry .  Mean systolic and diastolic BP were 122.6 and 77.9 mm Hg in the blacks , and 123.4 and 77.9 mm Hg in the whites , respectively . Plasma renin activity was significantly lower in the blacks compared to the whites ( 0.92 v 1.26 ng/mL/h , respectively , P < .05 ) , but ACE levels were similar in both groups ( 28.8 v 29.6 U/L , respectively ) . Renin activity was significantly and inversely associated with systolic and diastolic BP in both the blacks and the whites . ACE levels , however , were inversely associated with BP in the blacks but positively associated with BP in the whites ( P = .02 for interaction on diastolic BP ) , even after adjustment for age , gender , body mass index ( BMI ) , alcohol consumption , and heart rate . The corresponding interaction between ACE level and race on systolic BP was of borderline significance ( P = .06 ) . These results suggest that levels of ACE are similar in blacks and whites but their association with BP is possibly reflecting underlying ethnic differences in regulation of BP BACKGROUND Addition of spironolactone ( SPR ) to angiotensin-converting enzyme ( ACE ) inhibitors or angiotensin II receptor blockers ( ARBs ) might provide antiproteinuric effects beyond what is gained by either medication alone . This study was design ed to assess the long-term efficacy of SPR/ARB combination in comparison with the st and ard ACE/ARB regimen in diabetic nephropathy . METHODS In an open-label , parallel-group , single-center , r and omized clinical trial ( NCT01667614 ) , 136 patients with diabetes and proteinuria , already treated with enalapril and losartan , were included . In 74 patients , ACE inhibitors  were discontinued . After a wash-out period of 2 weeks , 25 mg SPR daily was initiated . The remainder of the patients ( n = 62 ) received ACE inhibitors and ARBs as before . Patients were followed every 3 months for 18 months . During each visit , systolic and diastolic blood pressure ( BP ) , urinary albumin excretion ( UAE ) , serum creatinine , estimated glomerular filtration rate ( eGFR ) and serum potassium concentrations were determined . RESULTS After 18 months , three patients in the SPR/ARB group developed asymptomatic hyperkalemia .  SPR/ARB significantly reduced both systolic and diastolic BP ( P < 0.001 and 0.001 , respectively ) . SPR/ARB  decreased UAE by 46 , 72 and 59 % after 3 , 12 and 18 months , respectively . Compared with the continuation regimen , SPR/ARB was superior in UAE reduction ( P = 0.017 after 18 months ) , independent of BP change . In both groups , eGFR declined significantly over the trial course and the decline rate did not differ significantly between the two groups . CONCLUSIONS Addition of SPR to ARB provides added benefits with respect to BP control and proteinuria diminution . These antiproteinuric effects are not accompanied by prevention of eGFR loss compared with conventional therapy with ACE/ARB Cilazapril ( CLZ ) is a new , long-acting nonsulfhydril converting enzyme inhibitor ( ACE-I ) . Its effect on peak and trough sitting diastolic blood pressure ( SDBP ) was studied in a total of 85 patients with uncomplicated , essential hypertension at three centers . After 4 weeks of a single-blind placebo ( PLA ) run-in period , patients whose SDBP was between 100 and 115 mm Hg , were r and omized into active treatment with either PLA ( n = 27 ) , CLZ 2.5 mg ( n = 29 ) , or CLZ 5 mg ( n = 29 ) once daily in a double-blind fashion for another 8 weeks . At the end of the PLA run-in and after 4 and 8 weeks active therapy , an hourly blood pressure ( BP ) profile during 1–10 and 21–24 h postdose was performed . The drop in SDBP at the end of the active treatment period at peak and trough was statistically and clinical ly significant for both CLZ doses in comparison with the PLA group . The peak/trough ratio after substraction of the PLA effect was 62 % for CLZ 2.5 mg and 59 % for CLZ 5 mg . These results indicate that the dose regimen of CLZ 2.5–5 mg once daily is adequate and effective for 24 OBJECTIVES Evaluation of the efficacy and safety of amlodipine in hypertensive children . STUDY DESIGN A r and omized , double blinded , placebo-controlled , parallel-group , dose-ranging study was conducted at 49 centers in North and South America . The primary end point was the effect of amlodipine on systolic blood pressure ( BP ) ; secondary end points included the effect of amlodipine on diastolic BP , the effect of amlodipine as a function of dose and body size , and evaluation of safety . RESULTS We enrolled 268 hypertensive children ( mean age , 12.1 + /- 3.3 years ) ; 84 ( 31.3 % ) had primary hypertension , and 177 ( 66 % ) were boys .  Amlodipine produced significantly greater reductions in systolic BP than placebo ; these were -6.9 mm Hg for 2.5 mg daily ( P=.045 vs placebo ) and -8.7 mm Hg for 5 mg daily ( P=.005 vs placebo ) . The underlying cause of hypertension had no effect on the response to amlodipine . There was a significant dose-response effect of amlodipine on both systolic and diastolic BP beginning at doses > or = 0.06 mg/kg per day . Systolic BP < or = 95(th ) percentile was achieved in 34.6 % of subjects with systolic hypertension . Amlodipine was well tolerated , with just 6 children withdrawn from treatment because of drug-related adverse events . CONCLUSIONS Amlodipine effectively lowers systolic BP in a dose-dependent manner in hypertensive children who require drug treatment Epidemiologic studies , animal models , and preliminary clinical trials in children implicate uric acid in the development of essential hypertension . Controversy remains as to whether the observations indicate a general mechanism or a surrogate phenomenon . We sought to determine whether uric acid is a causative mediator of increased blood pressure ( BP ) and impaired vascular compliance . We report a r and omized , double-blinded , placebo-controlled trial comparing 2 mechanisms of urate reduction with placebo in prehypertensive , obese , adolescents , aged 11 to 17 years . Subjects were r and omized to the xanthine oxidase inhibitor , allopurinol , uricosuric , probenecid , or placebo . Subjects treated with urate-lowering therapy experienced a highly significant reduction in BP . In clinic systolic BP fell 10.2 mm Hg and diastolic BP fell 9.0 mm Hg in treated patients compared with a rise of 1.7 mm Hg and 1.6 mm Hg systolic and diastolic BP , respectively in patients on placebo . Urate-lowering therapy also result ed in significant reduction in systemic vascular resistance . These data indicate that , at least in adolescents with prehypertension , uric acid causes increased BP that can be mitigated by urate lowering therapy Using digitized M-mode echocardiograms and 24-h ambulatory blood pressure ( BP ) monitoring , we compared the effects on left ventricle ( LV ) and BP of 6-month treatment with a calcium antagonist or an angiotensin-converting enzyme ( ACE ) inhibitor in 36 hypertensive patients with LV hypertrophy ( group 1 , 18 subjects treated with sustained-release isradipine ; group 2 , 18 subjects treated with perindopril ) . At the basal evaluation , the two groups had comparable BP and LV parameters . After treatment , both groups showed a similar and significant reduction in 24-h , day- and night-systolic and diastolic BP ( SBP , DBP ) . The reduction in LV mass index was greater ( p < 0.01 ) in group 2 . In group 1 , percentage of decrease of LV mass correlated significantly with percentage of decrease in 24-h and daytime BP ; this was not true of group 2 . Together with the reduction in LV hypertrophy , there was a significant increase of peak lengthening rate of LV diameter that was greater ( p < 0.01 ) in group 1 . Both drugs can reduce LV hypertrophy and improve diastolic function . The reduction of hypertrophy induced by perindopril appears to be partly independent of BP decrease and therefore partly related to a direct action of perindopril on the myocardium Background and Purpose — Angiotensin-converting enzyme ( ACE ) inhibitor – based therapy reduces the recurrence of stroke . The present study assessed the effects of long-term ACE inhibitor therapy on cerebral circulation in patients with previous minor stroke . Methods — After a run-in period , 19 patients were r and omized to ACE inhibitor therapy ( n=9 ; 4 mg of perindopril daily ; mean age , 64±8 years ; mean systolic/diastolic blood pressure [BP]±SD , 133±12/77±9 mm Hg ) or placebo therapy ( n=10 ; mean age , 66±9 years ; mean BP , 139±10/78±8 mm Hg ) . Cerebral blood flow ( CBF ) was measured during hypercapnia , normocapnia , and hypocapnia using a positron emission tomography with H215O at entry into the study and after 3 to 12 months . Cerebral perfusion reserve ( CPR ) was defined as percent CBF response to a 1 mm Hg change in arterial partial pressure of CO2 between hypercapnia and hypocapnia . Results — Systolic/diastolic BP and CBF during normocapnia showed no significant changes between entry and completion of the trial in the perindopril and placebo groups . Mean value of CPR showed a significant increase in the perindopril group ( from 3.7±1.7%/mm Hg to 4.8±1.7%/mm Hg ; P < 0.05 ) but not in the placebo group ( from 4.1±0.8%/mm Hg to 4.2±0.6%/mm Hg ; NS ) . Statistical parametric mapping analysis also showed global and significant increase ( P < 0.01 , uncorrected ) in CPR in the perindopril group alone . Conclusions — Long-term ACE inhibitor – based therapy had a beneficial effect on the cerebral circulation by improving CPR in patients with previous minor stroke Background — Diuretics are recommended as first-line agents for the treatment of hypertension . This r and omized , double-blind , multicenter study assessed the long-term efficacy and safety of the direct renin inhibitor aliskiren in comparison with the diuretic hydrochlorothiazide in patients with essential hypertension . Methods and Results — After a 2- to 4-week placebo run-in , 1124 patients ( mean sitting diastolic blood pressure [ BP ] 95 to 109 mm Hg ) were r and omized to aliskiren 150 mg ( n=459 ) , hydrochlorothiazide 12.5 mg ( n=444 ) , or placebo ( n=221 ) once daily . Forced titration ( to aliskiren 300 mg or hydrochlorothiazide 25 mg ) occurred at week 3 ; at week 6 , patients receiving placebo were reassigned ( 1:1 ratio ) to aliskiren 300 mg or hydrochlorothiazide 25 mg . From week 12 , amlodipine 5 mg was added and titrated to 10 mg from week 18 for patients whose BP remained uncontrolled . Efficacy variables were analyzed for the intent-to-treat population with the use of the last observation carried forward method . BP reductions ( mean sitting systolic BP/mean sitting diastolic BP ) were significantly greater with aliskiren- versus hydrochlorothiazide-based treatment at week 26 ( −20.3/−14.2 versus −18.6/−13.0 mm Hg ; P<0.05 ) and were also greater at week 52 ( −22.1/−16.0 versus −21.2/−15.0 mm Hg ; P<0.05 for mean sitting diastolic BP ) . At the end of the monotherapy period ( week 12 ) , aliskiren 300 mg was superior to hydrochlorothiazide 25 mg in reducing BP ( −17.4/−12.2 versus −14.7/−10.3 mm H ; P<0.001 ) . Adverse event rates were similar with aliskiren- ( 65.2 % ) and hydrochlorothiazide-based therapy ( 61.5 % ) . Hypokalemia was more frequent with hydrochlorothiazide-based therapy than aliskiren-based therapy ( 17.9 % versus 0.9 % ; P<0.0001 ) . Conclusions — Aliskiren treatment , both as monotherapy and with optional addition of amlodipine , provided significantly greater BP reductions than the respective hydrochlorothiazide regimens . Aliskiren-based therapy was well tolerated . Direct renin inhibition with aliskiren therefore represents an effective option for the long-term treatment of essential hypertension BACKGROUND It has been suggested that low diastolic blood pressure ( BP ) while receiving antihypertensive treatment ( hereinafter called on-treatment BP ) is harmful in older patients with systolic hypertension . We examined the association between on-treatment diastolic BP , mortality , and cardiovascular events in the prospect i ve placebo-controlled Systolic Hypertension in Europe Trial . METHODS Elderly patients with systolic hypertension were r and omized into the double-blind first phase of the trial , after which all patients received active study drugs ( phase 2 ) . We assessed the relationship between outcome and on-treatment diastolic BP by use of multivariate Cox regression analysis during receipt of placebo ( phase 1 ) and during active treatment ( phases 1 and 2 ) . RESULTS Rates of noncardiovascular mortality , cardiovascular mortality , and cardiovascular events were 11.1 , 12.0 , and 29.4 , respectively , per 1000 patient-years with active treatment ( n = 2358 ) and 11.9 , 12.6 , and 39.0 , respectively , with placebo ( n = 2225 ) . Noncardiovascular mortality , but not cardiovascular mortality , increased with low diastolic BP with active treatment ( P < .005 ) and with placebo ( P < .05 ) ; for example , hazard ratios for lower diastolic BP , that is , 65 to 60 mm Hg , were , respectively , 1.15 ( 95 % confidence interval , 1.00 - 1.31 ) and 1.28 ( 95 % confidence interval , 1.03 - 1.59 ) . Low diastolic BP with active treatment was associated with increased risk of cardiovascular events , but only in patients with coronary heart disease at baseline ( P < .02 ; hazard ratio for BP 65 - 60 mm Hg , 1.17 ; 95 % confidence interval , 0.98 - 1.38 ) . CONCLUSIONS These findings support the hypothesis that antihypertensive treatment can be intensified to prevent cardiovascular events when systolic BP is not under control in older patients with systolic hypertension , at least until diastolic BP reaches 55 mm Hg . However , a prudent approach is warranted in patients with concomitant coronary heart disease , in whom diastolic BP should probably not be lowered to less than 70 mm Hg Objective This study was design ed to assess the compliance of hypertensive patients with a once-daily regimen of the angiotensin converting enzyme ( ACE ) inhibitor tr and olapril  and to evaluate the antihypertensive efficacy of the drug in relation to the time interval between taking the final dose and measuring the blood pressure ( BP ) . Design After a 2-week wash-out period , hypertensive patients , recruited by cardiologists , received tr and olapril 2 mg once daily in the morning for 4 weeks . Methods In order to assess compliance , each patient 's supply of tr and olapril capsules was presented in a pillbox that incorporated in its lid a microprocessor that recorded the date and time of each occasion that it was opened . BP was measured using vali date d semi-automatic devices , at the end of both the wash-out and the treatment period . Results A total of 590 patients entered the study . Compliance data were evaluable for 501 patients .  Overall compliance , defined as the ratio of the number of openings recorded to the number of doses prescribed was less than 80 , 80–100 , and more than 100 % in 17 , 63 and 20 % of patients , respectively . The average number ( ± SD ) of missed doses was 4.5±8 ( median 2 ) . The average interval between successive openings was 25h 07 min mean±13h ( median 24h ) . The average number of delayed doses ( a delayed dose being defined as the box being opened 25–36 h after the previous occasion ) was 5.6±3 ( median 6 ) . Patients living in the Paris area had more forgotten and delayed doses than those living in the provinces ( 7.9 versus 3.8 forgotten ; P<0.0001 and 6.3 versus 5.5 delayed ; P<0.005 ) . Doses were forgotten and delayed more often during weekends than on weekdays . The greatest number of delayed doses occurred in those patients under 60 years of age ( 6.0 versus 5.2 ; P<0.01 ) . Decreases in systolic blood pressure ( SBP and diastolic blood pressure ( DBP ) were 20.3/12.8mmHg , for patients whose final drug was taken on the same day as the BP measurement , and 18.9/11.2mmHg for patients whose final dose was taken on the previous day . Conclusions Electronic compliance monitoring allows refined analysis of the behaviour of hypertensive patients . In this study doses were missed and delayed frequently during the first month of treatment , depending on the patient 's lifestyle BACKGROUND This study compared the effects of losartan and perindopril on plasma plasminogen activator inhibitor-1 ( PAI-1 ) and fibrinogen in hypertensive type 2 diabetic patients . METHODS We studied 85 nonsmoking out patients , aged 46 to 64 years , with mild to moderate essential hypertension ( diastolic blood pressure [ BP ] > 90 and < 110 mm Hg ) and well controlled type 2 diabetes mellitus . After a 4-week washout placebo period , patients were r and omized to received perindopril 4 mg once daily ( n = 42 ) or losartan 50 mg once daily ( n = 43 ) for 12 weeks according to a double-blind , parallel-group design . At the end of the placebo and active treatment periods , BP was measured and plasma PAI-1 and fibrinogen were evaluated . RESULTS Both perindopril and losartan reduced systolic and diastolic BP values ( -16/15 mm Hg and -15/14 , respectively ; P < .001 v placebo ) , with no difference between the two treatments . Plasma PAI-1 was reduced by perindopril ( -10 ng/dL , P = .028 v placebo ) but not by losartan ( + 4 ng/dL , NS ) , the difference between the two treatments being statistically significant ( P < .01 ) . Plasma fibrinogen showed no significant change with both drugs , although a decreasing trend was noted with perindopril . CONCLUSIONS These findings indicate that perindopril but not losartan decreases PAI-1 in hypertensive type 2 diabetic patients , which suggests that the PAI-1 lowering effect is unrelated with AT , receptor blockade and could rather be due to the fact that the endothelial receptors that mediate PAI-1 expression in response to angiotensin II are not type 1 receptor subtypes . Different effects of the two drugs on the bradykinin system might also be implicated We studied differences in the effects of a long-acting angiotensin-converting enzyme ( ACE ) inhibitor ( temocapril ) and a long-acting calcium channel blocker ( amlodipine ) on ventricular ectopic beats ( VEB ) in relation to sympathetic nerve activity in 46 patients with essential hypertension . We performed 24-h Holter electrocardiography and ambulatory blood pressure ( BP ) monitoring simultaneously , and examined blood sample s during the baseline , temocapril and amlodipine treatment periods . The ambulatory BP was lower in the amlodipine period than in the temocapril period . However , the number of VEB was significantly increased in the amlodipine period compared to that in the baseline period ( 11.9 vs. 7.4/day , p<0.05 ) . In the temocapril period , the number of VEB was not significantly increased compared to that in the baseline period ( 8.6 vs. 7.4/day , p=0.30 ) . Ambulatory heart rate ( HR ) was significantly increased in the amlodipine period compared to that in the baseline period ( 24-h HR : 70 vs. 66 bpm , p<0.001 ; daytime HR : 75 vs. 71 bpm , p<0.001 ; nocturnal HR : 60 vs. 58 bpm , p<0.05 ) . Plasma norepinephrine ( NE ) also was significantly increased in the amlodipine period compared to that in the baseline period ( 457 vs. 369 pg/ml , p<0.001 ) . However , when patients receiving amlodipine were divided into a high dose group ( 8.6 + /- 1.2 mg/day ) and a low dose group ( 4.6 + /- 1.2 mg/day ) , increases in HR and plasma NE levels were found only in the high dose group . These results indicate that amlodipine is effective at lowering BP in older hypertensives , although it may increase VEB , especially when given at a high dose Introduction : Losartan potassium , an orally active , highly selective AT1 angiotensin II receptor inhibitor , effectively reduces blood pressure by direct receptor blockade , thereby lessening the likelihood of angiotensin converting enzyme ( ACE ) inhibitorassociated side effects such as dry cough or possibly angioedema Study design : In this multinational , double-blind , r and omized , parallel study , the efficacy and tolerability of once-daily losartan ( 50 mg ) versus once-daily ACE inhibitor ( captopril ; 50 mg ) was evaluated in 163 patients with mild to moderate hypertension . Non-responders after a 6-week treatment period had the dosage doubled for both study drugs until the end of study ( week 12 ) Results : Mean reductions in trough sitting diastolic blood pressure were significantly greater in the losartan group at week 6 ( 7.8 mmHg ) and week 12 ( 9.1 mmHg ) than in the captopril group ( 5.2 and 5.7 mmHg , respectively ) . Losartan and captopril were well tolerated . Headache was the most common adverse event reported in both groups Conclusions : It was concluded that a once-daily administration of losartan was significantly more effective in this study in lowering sitting diastolic blood pressure than once-daily administration of captopril in patients with mild to moderate essential hypertension . Both losartan and captopril regimes were well BACKGROUND Even within the normal range , aldosterone levels are linked to end-organ toxicity and mortality in patients with hypertension . Treatment with angiotensin-converting enzyme inhibitors or angiotensin-receptor blockers does not sufficiently reduce plasma aldosterone levels . OBJECTIVE This study was conducted to assess the long-term safety profile and efficacy of the selective aldosterone blocker eplerenone . METHODS This was a multicenter , open-label , uncontrolled trial in patients with mild to moderate essential hypertension . After a 1-week washout of previous antihypertensive medications , eplerenone was initiated at 50 mg once daily ; the dose was titrated to a maximum of 200 mg/d to achieve a diastolic blood pressure < 90 mm Hg and a systolic blood pressure < 140 mm Hg . Thereafter , another antihypertensive agent could be added and titrated once , or another agent could be substituted for eplerenone . Eplerenone treatment was continued for up to 14 months in a subset of patients . RESULTS Five hundred eighty-six patients were enrolled in the study . Their adjusted mean blood pressure ( BP ) at baseline was 150/96 mm Hg . The majority ( 80.4 % ) were white ; 51.5 % were male and 48.5 % were female ; 62.3 % were between the ages of 45 and 64 years and 21.7 % were aged > 64 years . Three hundred eighty-five patients ( 65.7 % ) completed the study ; 98 ( 16.7 % ) were withdrawn due to treatment failure ( only 4.8 % of them after month 4 ) , and 40 ( 6.8 % ) were withdrawn due to treatment-emergent adverse events . Four hundred thirty-three of 582 ( 74.4 % ) patients in the intent-to-treat population achieved BP control during eplerenone treatment : 261 ( 44.8 % ) received eplerenone monotherapy and 172 ( 30.0 % ) received eplerenone plus another antihypertensive agent . CONCLUSIONS Eplerenone therapy was effective in the treatment of mild to moderate hypertension over a 14-month period , either as monotherapy or in combination with another antihypertensive agent . Use of eplerenone was well tolerated in the population studied Objective : To perform a subgroup analysis on those patients in STOP‐Hypertension‐2 who had isolated systolic hypertension . Design and methods : The STOP‐Hypertension‐2 study evaluated cardiovascular mortality and morbidity in elderly hypertensives comparing treatment with conventional drugs ( diuretics , beta‐blockers ) with that of newer ones [ angiotensin‐converting enzyme ( ACE ) inhibitors , calcium antagonists ] . In all , 6614 elderly patients with hypertension ( mean age 76.0 years , range 70–84 years at baseline ) were included in STOP‐Hypertension‐2 . In the present subgroup analysis of STOP‐Hypertension‐2 , isolated systolic hypertension was defined as systolic blood pressure at least 160 mmHg and diastolic blood pressure below 95 mmHg , in accordance with the Syst‐Eur and Syst‐China study criteria . In total , 2280 patients in STOP‐Hypertension‐2 met these criteria . In the study , patients were r and omized to one of three treatment groups : “ conventional ” antihypertensive therapy with beta‐blockers or diuretics ( atenolol 50 mg , metoprolol 100 mg , pindolol 5 mg , or fixed‐ratio hydrochlorothiazide 25 mg plus amiloride 2.5 mg daily ) ; ACE inhibitors ( enalapril 10 mg or lisinopril 10 mg daily ) ; or calcium antagonists ( felodipine 2.5 mg or isradipine 2.5 mg daily ) . Analysis was by intention to treat . Results : The blood pressure lowering effect in patients with systolic hypertension was similar with all three therapeutic regimens : 35/13 mmHg in the conventional group ( n = 717 ) , 34/12 mmHg in the ACE inhibitor group ( n = 724 ) , and 35/13 mmHg in the calcium antagonist group ( n = 708 ) . Prevention of cardiovascular mortality , the primary endpoint of the study , did not differ between the three treatment groups . All stroke events , i.e. fatal and non‐fatal stroke together , were significantly reduced by 25 % in the newer‐drugs group compared with the conventional group ( 95 % CI 0.58–0.97 ; p = 0.027 ) . This difference was attributable to reduction of non‐fatal stroke while fatal stroke events did not differ between groups . New cases of atrial fibrillation were significantly increased by 43 % ( 95 % CI 1.02–1.99 ; p = 0.037 ) on “ newer ” drugs compared with “ conventional ” therapy , mainly attributable to the calcium antagonists . There were no significant differences between the three treatment groups with respect to the risks of myocardial infa rct ion , sudden death or congestive heart failure . Conclusions : The analysis demonstrated that “ newer ” therapy ( ACE inhibitors/calcium antagonists ) was significantly better ( 25 % ) than “ conventional ” ( diuretics/beta‐blockers ) in preventing all stroke in elderly patients with isolated systolic hypertension We assessed blood pressure ( BP ) and heart rate ( HR ) responses in a double‐blind , r and omized study comparing cilazapril , a long‐acting , nonsulfhydryl‐group converting enzyme inhibitor , with placebo in 18 patients with mild to moderate ( sitting diastolic BP , 95 to 114 mm Hg ) essential hypertension .  The BP and HR parameters were evaluated at rest ( casual , 24 hours after administration ) , during treadmill exercise testing ( Bruce protocol ) , and with 24‐hour noninvasive ambulatory BP monitoring . These assessment s were made after a 4‐week drug washout period and after 8 to 12 weeks of therapy . After 8 weeks of therapy with cilazapril ( mean dose 3.6 ± 0.9 mg/day ) , casual BP decreased 19/11 mm Hg ( p < 0.01 ) , whereas placebo  lowered BP by 4/5 mm Hg ( difference not significant ) compared with the baseline period . The casual HR was modestly ( 7 beats/min ) but significantly ( p < 0.05 ) lowered by cilazapril  monotherapy . Exercise BP was reduced by cilazapril ( reduction at peak HR , 23/11 ± 10/5 mm Hg ; p < 0.05 ) , and exercise HR was unchanged . Compared with baseline , the duration of exercise was improved with cilazapril but not with placebo ( 1.0 minute vs − 0.2 minute ; p < 0.05 ) . Twenty‐four‐hour mean , awake , and sleep BPs were reduced with cilazapril with the most impressive reduction occurring during the awake period ( 19/12 mm Hg ; p < 0.01 ) . These data demonstrate  that cilazapril  lowers casual , exercise , and ambulatory BP with a modest but significant improvement in exercise time . Thus cilazapril may be particularly effective in the physically active hypertensive patient Antihypertensive agents may , even within the same class , exert variable effects on arterial stiffness variables .  Nebivolol could have a better impact than atenolol on arterial stiffness , by increasing the bioavailability of endothelium-derived nitric oxide . Angiotensin-converting enzyme inhibitors ( ACEIs ) and angiotensin receptor blockers ( ARBs ) increase plasma renin activity ( enhancing the production of angiotensin II via non-ACE-related pathways ) whereas aliskiren does not , potentially affecting central hemodynamics differently . We compared the effects of two renin-angiotensin-aldosterone system ( RAAS ) inhibitors ( quinapril and aliskiren ) and 2 beta-blockers ( atenolol and nebivolol ) on arterial stiffness variables . Treatment-naïve patients ( n = 72 ; 68.1 % males ; age , 47.6 ± 10.6 years ) with uncomplicated stage I-II essential hypertension were r and omly assigned to quinapril , aliskiren , atenolol , or nebivolol for 10 weeks . Central systolic and diastolic blood pressure ( BP ) , central pulse pressure ( PP ) , augmentation index ( AIx ) , and pulse wave velocity ( PWV ) were measured at baseline , 2 , and 10 weeks . The same measurements were performed in 20 normotensive subjects ( 65.0 % males ; age , 40.0 ± 8.9 years ) . Peripheral and central systolic and diastolic BP , peripheral PP , and PWV were significantly and similarly reduced by all agents . However , PWV continued to decline between the second and last visit in patients on quinapril and aliskiren but did not change in those on nebivolol or atenolol  . Central PP and AIx decreased in patients on quinapril , aliskiren , and nebivolol but did not change in those taking atenolol . The decrease in central PP and AIx did not differ between patients on quinapril , aliskiren , and nebivolol . Despite similar reductions in peripheral BP , atenolol is less effective than nebivolol and RAAS inhibitors in improving central pulsatile hemodynamics . Aliskiren exerts similar effects on markers of arterial stiffness  as quinapril . The clinical relevance of these differences remains to be established Background and Objectives Obesity exacerbates hypertension and stimulates the renin – angiotensin – aldosterone system ( RAAS ) . Full-dose RAAS inhibition could be a therapeutic option in overweight or obese patients with hypertension . This study compared four RAAS inhibitors at full therapeutic doses to determine their effect on blood pressure ( BP ) and cardiovascular risk factors in these patients . Methods We conducted a 24-week , single-blind , r and omized , parallel-group study in 120 overweight or obese patients ( body mass index ≥27 kg/m2 ) with hypertension , aged 18–60 years . The primary endpoint was the change in mean 24-h systolic BP and diastolic BP from baseline to study end . Central BP , arterial stiffness , and metabolic and cardiac indices were also investigated . Patients were r and omly allocated to perindopril 10 mg/day , enalapril 20 mg/day , losartan 100 mg/day or telmisartan 80 mg/day . Nonpharmacological interventions were also recommended . Results Reductions in mean 24-h systolic BP ( and diastolic BP ) were all significant ( p < 0.05 versus baseline ) for perindopril , enalapril , losartan and telmisartan  : systolic BP −22 , −11 , −12 and −15 mmHg , respectively ; ( and diastolic BP −13 , −6 , −13 and −12 mmHg , respectively ) . Aortic elasticity improved with perindopril and telmisartan . Perindopril was associated with the greatest reductions in central aortic BP and leptin levels [ 30 % versus 2 % , 7 % and 14 % with enalapril , losartan and telmisartan , respectively ( all p < 0.05 versus perindopril ) ] . Reductions in other BP , echocardiographic , metabolic and anthropometric parameters occurred with all treatments . Conclusion Full-dose RAAS inhibition , particularly with perindopril , effectively reduces BP , improves arterial structure and regulates cardiovascular risk factors in overweight or obese patients with hypertension The antihypertensive efficacy and safety of the direct renin inhibitor aliskiren were assessed in a pooled analysis of data from seven r and omized , multicenter studies . Data were available for 7,045 patients ( mean age 52.5 to 59.8 years , 50.2 to 72.5 % men ) with mild-to-moderate hypertension ( mean sitting diastolic blood pressure [ msDBP ] 95 to 109 mm Hg ) over treatment duration s of 6 to 8 weeks . In placebo-controlled trials , aliskiren reduced mean sitting systolic blood pressure/msDBP from baseline by 8.6 to 12.1/7.2 to 10.3 mm Hg ( 75 mg ) , 8.7 to 13.0/7.8 to 10.3 mm Hg ( 150 mg ) , 14.1 to 15.8/10.3 to 12.3 mm Hg ( 300 mg ) , and 15.7 to 15.8/11.5 to 12.5 mm Hg ( 600 mg ) , compared with 2.9 to 10.0/3.3 to 8.6 mm Hg for placebo . Aliskiren demonstrated comparable efficacy in men and women , in patients aged < 65 years or > /=65 years , and lowered blood pressure ( BP ) effectively in all racial subgroups . Combination of aliskiren 150 mg or 300 mg with ramipril , amlodipine , or hydrochlorothiazide  provided significant additional BP reductions compared with the respective monotherapies . The overall incidence of adverse events with aliskiren monotherapy was similar to placebo ( 39.8 % vs. 40.2 % , respectively ) . The incidence of diarrhea with aliskiren was higher than placebo due to a significantly higher rate with aliskiren 600 mg ( P < .0001 vs. placebo ) . In conclusion , aliskiren 150 mg or 300 mg provides highly effective and consistent BP lowering with placebo-like tolerability in patients with mild-to-moderate hypertension CONTEXT Few cardiovascular outcome data are available for blacks with hypertension treated with angiotensin-converting enzyme ( ACE ) inhibitors or calcium channel blockers ( CCBs ) . OBJECTIVE To determine whether an ACE inhibitor or CCB is superior to a thiazide-type diuretic in reducing cardiovascular disease ( CVD ) incidence in racial subgroups . DESIGN , SETTING , AND PARTICIPANTS Prespecified subgroup analysis of ALLHAT , a r and omized , double-blind , active-controlled , clinical outcome trial conducted between February 1994 and March 2002 in 33,357 hypertensive US and Canadian patients aged 55 years or older ( 35 % black ) with at least 1 other cardiovascular risk factor . INTERVENTIONS Antihypertensive regimens initiated with a CCB ( amlodipine ) or an ACE inhibitor ( lisinopril ) vs a thiazide-type diuretic ( chlorthalidone ) . Other medications were added to achieve goal blood pressures ( BPs ) less than 140/90 mm Hg . MAIN OUTCOME MEASURES The primary outcome was combined fatal coronary heart disease ( CHD ) or nonfatal myocardial infa rct ion ( MI ) , analyzed by intention-to-treat . Secondary outcomes included all-cause mortality , stroke , combined CVD ( CHD death , nonfatal MI , stroke , angina , coronary revascularization , heart failure [ HF ] , or peripheral vascular disease ) , and end-stage renal disease . RESULTS No significant difference was found between treatment groups for the primary CHD outcome in either racial subgroup . For amlodipine vs chlorthalidone only , HF was the only prespecified clinical outcome that differed significantly ( overall : relative risk [ RR ] , 1.37 ; 95 % confidence interval [ CI ] , 1.24 - 1.51 ; blacks : RR , 1.46 ; 95 % CI , 1.24 - 1.73 ; nonblacks : RR , 1.32 ; 95 % CI , 1.17 - 1.49 ; P<.001 for each comparison ) with no difference in treatment effects by race ( P = .38 for interaction ) . For lisinopril vs chlorthalidone , results differed by race for systolic BP ( greater decrease in blacks with chlorthalidone ) , stroke , and combined CVD outcomes ( P<.001 , P = .01 , and P = .04 , respectively , for interactions ) . In blacks and nonblacks , respectively , the RRs for stroke were 1.40 ( 95 % CI , 1.17 - 1.68 ) and 1.00 ( 95 % CI , 0.85 - 1.17 ) and for combined CVD were 1.19 ( 95 % CI , 1.09 - 1.30 ) and 1.06 ( 95 % CI , 1.00 - 1.13 ) . For HF , the RRs were 1.30 ( 95 % CI , 1.10 - 1.54 ) and 1.13 ( 95 % CI , 1.00 - 1.28 ) , with no significant interaction by race . Time-dependent BP adjustment did not significantly alter differences in outcome for lisinopril vs chlorthalidone in blacks . CONCLUSIONS In blacks and nonblack subgroups , rates were not lower in the amlodipine or lisinopril groups than in the chlorthalidone group for either the primary CHD or any other prespecified clinical outcome , and diuretic-based treatment result ed in the lowest risk of heart failure . While the improved outcomes with chlorthalidone were more pronounced for some outcomes in blacks than in nonblacks , thiazide-type diuretics remain the drugs of choice for initial therapy of hypertension in both black and nonblack hypertensive patients Limited evidence suggests renin – angiotensin – aldosterone system ( RAAS ) polymorphisms alter the blood pressure ( BP ) response to aerobic exercise training . We examined if RAAS polymorphisms influenced postexercise hypotension in men with high normal to Stage 1 hypertension . Forty-seven men ( 44.2±1.4 years , 145.1±1.6/85.5±1.1 mmHg ) r and omly completed three experiments : seated rest ( control ) and two cycle exercise bouts at 40 % ( LITE ) and 60 % ( MOD ) of maximal oxygen consumption  . Ambulating BP  was measured for 14 h after each experiment . RAAS polymorphisms associated with hypertension ( i.e. angiotensin converting I enzyme , ACE I/D ; angiotensin II type 1 receptor , AT1R A/C ; and intron 2 of aldosterone synthase , Int2 W/C ) were analyzed using polymerase chain reaction and restriction enzyme digestion . Repeated measure ANOVA tested if BP differed between experimental conditions by RAAS genotypes . Compared to men with 0–2 variant alleles , men with ≥3 combined RAAS variant alleles had lower average systolic BP ( SBP ) ( P=0.030 ) and lower average diastolic BP ( DBP ) ( P=0.009 ) for 14 h only after LITE . In contrast , average BP was not different for MOD and control between RAAS variant allele groups over this time period ( P≥0.05 ) . LITE reduced BP in men with ≥3 variant RAAS alleles for 14 h , whereas MOD had no influence on BP in these men . In order to optimally prescribe exercise for its BP lowering benefits in those with hypertension , additional knowledge of how genetic variation affects the BP response  to exercise is needed Nigella sativa L. seeds ( N. sativa ) have been used as a traditional remedy for a wide range of diseases including hypertension . The present study was performed to explore the effects of N. sativa oil on blood pressure ( BP ) in healthy volunteers . In a double-blind , r and omized study , 70 healthy volunteers aged 34 to 63 years with systolic BP from 110 to 140 mmHg and diastolic BP from 60 to 90 mmHg were r and omly allocated to receive 2.5 mL N. sativa oil or placebo two times a day for 8 weeks . The systolic and diastolic BPs , body mass index and blood levels of aspartate transaminase , alanine transaminase , alkaline phosphatase , creatinine and blood urea nitrogen were determined at baseline and endpoint . Results showed that in N. sativa oil treated group the systolic and diastolic BPs decreased significantly compared with baseline and placebo group at the endpoint . Other parameters did not significantly change in both groups at the endpoint . No adverse effects were reported . In conclusion , oral daily administration of 5 mL N. sativa oil to healthy volunteers for 8 weeks lowers systolic and diastolic BPs without any adverse effects The safety and efficacy of an extended-release form of diltiazem HCl ( diltiazem XR ) in patients 55 years or older with mild-to-moderate essential hypertension were examined in a multi-center , double-blind , r and omized , placebo-controlled , parallel-group study involving 350 patients with supine diastolic blood pressure ( DBP ) between 95 mm Hg and 114 mm Hg . Patients were r and omized to a once-daily dose of diltiazem XR ( 240 mg ) or placebo ; 261 patients received diltiazem XR and 89 received placebo . After 4 weeks , the dose was doubled ( to 480 mg ) in patients whose supine DBP was > 90 mm Hg , and treatment was continued for another 4 weeks . Diltiazem XR consistently reduced blood pressure ( BP ) in the study population . At end-point , the mean reduction in supine DBP was 8.65 mm Hg in the diltiazem XR group and 2.75 mm Hg in the placebo group ( P < 0.0001 ) . Subgroup analysis confirmed the efficacy of diltiazem XR in men , women , patients between the ages of 55 and 64 years , patients 65 years or older , and non-black patients . Other BP values ( supine systolic , st and ing diastolic , and st and ing systolic ) also were significantly reduced in patients treated with diltiazem XR . BP reduction ( supine DBP < or = 90 mm Hg or by > or = 10 mm Hg ) was achieved in 58 % of patients receiving diltiazem XR compared with 27 % of patients receiving placebo . Decreases in apical heart rate were minimal and similar in both groups . No significant differences were noted in adverse events in the diltiazem XR and placebo groups : 36.4 % of patients in the diltiazem XR group and 37.1 % in the placebo group had no adverse experiences , and 63.6 % and 62.9 % , respectively , had at least one adverse event . Physical examination findings and laboratory values were clinical ly unremarkable and comparable in the diltiazem XR and placebo groups . Diltiazem XR given once daily at doses of 240 mg and 480 mg was safe and effective in lowering blood pressure in mature and elderly patients with mild-to-moderate hypertension This study examined the association between T1198C polymorphism of the angiotensinogen ( AGT ) gene and the blood pressure response to ACE inhibitors in a Chinese hypertensive cohort . After a 2-week single-blind placebo run-in period , benazepril ( 10–20 mg/day ) or imidapril ( 5–10 mg/day ) was administered for 6 weeks to 509 patients with mild-to-moderate essential hypertension .  Polymerase chain reaction combined with restriction enzyme digestion was used to detect the polymorphism , and the patients were classified as having the TT , TC , or CC genotype . The achieved changes in systolic and diastolic blood pressure ( SBP and DBP ) were analyzed to determine their association with genotypes at the AGT gene locus . In the total 509 patients , the TT genotype was observed in 44 patients ( 8.7 % ) , the TC genotype in 214 patients ( 42.0 % ) , and the CC genotype in 251 patients ( 49.3 % ) . The SBP reductions in patients with the TT genotype , TC genotype , and CC genotype were −15.3±12.7 mmHg , −14.0±12.7 mmHg , and −14.4±12.4 mmHg , respectively ( p=0.809 ) . The DBP reductions in patients with the TT genotype , TC genotype , and CC genotype were −8.5±8.1 mmHg , −8.3±7.5 mmHg , and −8.9±6.6 mmHg , respectively ( p=0.638 ) . There were no significant differences in the changes in SBP or DBP after treatment among the three genotype groups . In conclusion , these results suggest that the AGT genotype does not predict the blood pressure-lowering response to antihypertensive treatment with ACE inhibitors in Chinese hypertensive patients 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 Previous studies have shown that the selective aldosterone blocker eplerenone , in doses of up to 200 mg/d , reduces albuminuria in patients with type 2 diabetes . This study was conducted to ascertain whether lower doses of eplerenone ( 50 or 100 mg/d ) co-administered with the angiotensin-converting enzyme ( ACE ) inhibitor enalapril would produce a similar antialbuminuric effect while obviating the hyperkalemia observed previously . After open-label run-in with enalapril 20 mg/d , patients with diabetes and a urinary albumin : creatinine ratio ( UACR ) > or = 50 mg/g were r and omly assigned to receive enalapril plus one of three double-blind daily treatments for 12 wk : placebo , eplerenone 50 mg ( EPL50 ) , or eplerenone 100 mg ( EPL100 ) . After week 4 , amlodipine 2.5 to 10 mg/d was allowed for BP control ( systolic/diastolic BP < or = 130/80 mmHg ) . The primary study end points were the percentage change from baseline at week 12 in UACR and the incidence of hyperkalemia . Secondary end points included percentage changes from baseline in UACR at weeks 4 and 8 and changes from baseline in systolic and diastolic BP . Treatment with EPL50 or EPL100 but not placebo significantly reduced albuminuria from baseline . By week 12 , UACR was reduced by 7.4 % in the placebo group , by 41.0 % in the EPL50 group , and by 48.4 % in the EPL100 group ( both eplerenone groups , P < 0.001 versus placebo ) . The incidences of sustained and severe hyperkalemia were not significantly different in any of the three treatment arms and did not differ on the basis of quartile of estimated GFR ( all NS ) . For the secondary end points , both eplerenone treatment groups significantly reduced albuminuria from baseline as early as week 4 ( P < 0.001 ) , whereas placebo treatment ( including enalapril ) did not result in any significant decreases in UACR . Systolic BP decreased significantly in all treatment groups at all time points , but , generally , all treatment groups experienced similar decreases in BP . Co-administration of EPL50 or EPL100 with an ACE inhibitor as compared with an ACE inhibitor alone significantly reduces albuminuria in patients with diabetes without producing significant increases in hyperkalemia This multicenter study evaluated the efficacy of c and esartan cilexetil , an angiotensin II type 1 receptor antagonist , used alone or in combination with amlodipine or in combination with amlodipine and hydrochlorothiazide in the treatment of patients with moderate-to-severe essential hypertension . After a 2-week , single-blind , placebo run-in period , patients entered a 12-week , open-label , dose-titration period . The c and esartan cilexetil dose was increased from 8 to 16 mg once daily ; amlodipine ( 5 mg once daily ) , hydrochlorothiazide ( 25 mg once daily ) , and additional medication were also added sequentially if necessary . Patients then entered a final 4-week , parallel-group , double-blind , r and omized , placebo-controlled withdrawal period of c and esartan alone .  A total of 216 patients were recruited . After a 2-week run-in period on placebo tablets , mean sitting blood pressure ( BP ) was 175/108 mm Hg . At the end of the 12-week dose-titration/maintenance period , mean sitting BP fell to 141/88 mm Hg . In 67 patients who were r and omized to placebo and had their c and esartan withdrawn , there was a highly significant increase in mean systolic/diastolic BP ( 13/6 mm Hg ) compared with those patients who continued with c and esartan ( ANCOVA , P < 0.0001 ) . In conclusion , c and esartan cilexetil is an effective BP-lowering drug when used alone or in combination with amlodipine or amlodipine plus hydrochlorothiazide in the treatment of moderate-to-severe essential hypertension . The drug was well tolerated throughout the investigation period Objective : To compare the antihypertensive efficacy of moexipril , a new angiotensin-converting enzyme ( ACE ) inhibitor , to treatment with hydrochlorothiazide ( HCTZ ) . Patients : Two hundred and one non-hospitalized male and female patients between 65 and 80 years of age with essential hypertension . Methods : This was a multicentre , placebo-controlled , double-blind study with a parallel group design . Subjects with a sitting diastolic blood pressure ( DBP ) ≥ 95 mmHg were r and omized to monotherapy with placebo , moexipril 7.5 mg o.d . , moexipril 15 mg o.d . or HCTZ 25 mg o.d . for 8 weeks . Results : Throughout the study period treatment with moexipril and HCTZ result ed in significant reductions of DBP compared with placebo , but there were no significant differences between the active treatment groups . At end point the adjusted mean reductions were 10.5 , 8.7 and 10.1 mmHg in the HCTZ , moexipril 7.5 mg and moexipril 15 mg groups , respectively , compared to 3.9 mmHg in the placebo group . Treatment with moexipril was associated with two cases of first dose hypotension and two cases of moderate and reversible increases in serum creatinine levels . Otherwise , both dosages of moexipril were well tolerated and the overall percentages of patients who had adverse experiences were smaller than in the placebo group . Conclusion : Moexipril is well tolerated and is at least as effective as HCTZ in elderly patients with essential hypertension Quinapril HCl is a novel , nonsulf hydryl angiotensin-converting en zyme ( ACE ) inhibitor . The Study Group evaluated its efficacy ( 20 , 40 , 80 mg daily with forced dose titration determination at trough blood pres sure ) once daily versus twice daily versus placebo , as well as its tolera bility and safety , in 270 patients with mild to moderate essential hyperten sion ( WHO Stages I and II , sitting diastolic blood pressure [ DPB ] ≥95 mm Hg ) , for twelve weeks . Reduc tions in DBP of up to 13 mm Hg were obtained , and in full dosage more than 65 % of patients achieved a re duction in DBP of 10 mm Hg or more from baseline or reduced their DBP to 90 mm Hg or less  . Quinapril was well tolerated , and reported adverse effects were scarcely more frequent than in the placebo group . Once daily doses of quinapril were as safe and effective as twice-daily doses . Quina pril is likely to exhibit good therapeu tic utility in the management of essential hypertension BACKGROUND When blood pressure (BP)-lowering efficacy is assessed by measurements taken in a clinic setting , angiotensin II-receptor antagonists show similar efficacy to angiotensin-converting enzyme inhibitors and better tolerability . A search of MEDLINE to date , however , reveals no r and omized , double-blind studies using ambulatory BP monitoring ( ABPM ) to compare the BP-lowering efficacy of irbesartan and enalapril in a large number of patients ( > 200 ) with essential hypertension . OBJECTIVE This study compared 24-hour BP reduction and BP control , as assessed by ABPM , in patients with mild to moderate essential hypertension treated with irbesartan or enalapril .  The relative tolerability of the 2 treatments was also evaluated . METHODS This was a multicenter , r and omized , double-blind study in patients with mild to moderate essential hypertension ( office diastolic BP [ DBP ] 90 - 109 mm Hg or systolic BP [ SBP ] 140 - 179 mm Hg ) . After a 3-week , single-blind placebo washout phase , patients with a mean daytime DBP > or = 85 mm Hg , as measured by ABPM between 10 AM and 8 PM , were r and omized to 12 weeks of active treatment with irbesartan or enalapril . Starting doses were 150 and 10 mg/d , respectively , with titration to 300 or 20 mg/d if clinic DBP was > or = 90 mm Hg at week 4 or 8 . Based on clinic measurements , BP control was defined as a BP reading < 140/90 mm Hg after 12 weeks of treatment ; patients achieving a reduction in DBP of > or = 10 mm Hg at 12 weeks were considered responders . The ABPM criterion for BP control , independent of clinic values , was achievement of a daytime BP < 130/85 mm Hg after 12 weeks of treatment ; patients achieving a reduction in 24-hour DBP > or = 5 mm Hg at 12 weeks were considered responders , in dependent of clinic values . RESULTS A total of 238 patients were r and omized to treatment , 115 to irbesartan and 123 to enalapril . The study population was approximately 52.0 % female and 48.0 % male , with a mean ( + /- SD ) age of 52.7 + /- 10.6 years . The study was completed by 111 patients in the irbesartan group ( dose titrated to 300 mg/d in 72.0 % of patients ) and 115 patients in the enalapril group ( dose titrated to 20 mg/d in 76.5 % of patients ) . BP reductions were similar in the 2 groups , both as measured in the clinic ( DBP , 12.7 + /- 8.8 mm Hg irbesartan vs 12.4 + /- 7.4 mm Hg enalapril ; SBP , 19.0 + /- 14.1 mm Hg vs 17.5 + /- 14.0 mm Hg ) and by 24-hour ABPM ( DBP , 9.4 + /- 8.5 mm Hg vs 8.8 + /- 8.5 mm Hg : SBP , 14.7 + /- 14.7 mm Hg vs 12.6 + /- 13.1 mm Hg ) . As assessed by ABPM , rates of BP control were 40.5 % ( 45/111 ) for irbesartan and 33.9 % ( 39/115 ) for enalapril , and the response rates were a respective 71.2 % ( 79/111 ) and 71.3 % ( 82/115 ) . The overall incidence of adverse events ( 40.0 % irbesartan , 51.2 % enalapril ) was not statistically different between groups , although the incidence of adverse events considered probably related to antihypertensive treatment was significantly higher with enalapril than with irbesartan ( 24.6 % vs 9.2 % , respectively ; P = 0.026 ) , essentially because of the higher incidence of cough ( 8.1 % vs 0.9 % ) . CONCLUSIONS As assessed by ABPM , irbesartan 150 to 300 mg/d was as effective in lowering BP and achieving BP control as enalapril 10 to 20 mg/d . Based on the number of treatment-related adverse events , irbesartan was better tolerated than enalapril BACKGROUND Reducing systolic blood pressure ( BP ) is of major benefit to patients with isolated systolic hypertension , but lowering normal diastolic BP may be harmful in terms of cardiovascular risk . Effects of different drugs on systolic BP , diastolic BP , and pulse pressure are therefore of interest . METHODS The NatriliX SR versus C and Esartan and amLodipine in the reduction of systoLic blood prEssure in hyperteNsive patienTs study ( X-CELLENT ) was a r and omized , double-blind , placebo-controlled study comparing the effects of three drugs on these BP components . Patients with systolic-diastolic or isolated systolic hypertension ( n = 1758 ) received indapamide ( 1.5 mg ) sustained release ( SR ) , c and esartan ( 8 mg ) , amlodipine ( 5 mg ) , or placebo once daily for 12 weeks . RESULTS Compared to placebo all active treatments reduced all BP components significantly ( P < .001 ) . For the patients with isolated systolic hypertension ( n = 388 ) , the three treatments significantly reduced systolic BP , but only indapamide SR did not change diastolic BP and thus reduced pulse pressure significantly relative to placebo ( P = .005 ) . In an ancillary study using ambulatory BP monitoring ( n = 576 ) , all three treatments significantly reduced BP components during 24 h relative to placebo . Changes in systolic BP and pulse pressure were similar with the three treatments , but the reduction in diastolic BP was significantly smaller , and therefore more favorable , with indapamide SR compared with c and esartan ( P = .039 ) . In patients with isolated systolic hypertension ( n = 106 ) , indapamide SR reduced 24-h systolic BP significantly more than amlodipine ( P = .037 ) , and only indapamide SR reduced 24-h pulse pressure significantly relative to placebo ( P = .03 ) . All three drugs were well tolerated . CONCLUSIONS This distinctive BP-lowering profile of indapamide SR seems highly beneficial when compared to the either of c and esartan or amlodipine A large-scale , 8-week , open-label , clinical experience trial evaluated the efficacy of the angiotensin II receptor ( AT1 subtype ) blocker c and esartan cilexetil ( 16 to 32 mg once daily ) either alone or as add-on therapy in 6465 hypertensive patients . The study population was 52 % female and 16 % African American with a mean age of 58 years . It included 5,446 patients who had essential hypertension ( HBP ) and 1,014 patients who had isolated systolic hypertension ( ISH ) . These patients had either untreated or uncontrolled hypertension ( systolic blood pressure [ SBP ] 140 to 179 mm Hg or diastolic blood pressure [ DBP ] 90 to 109 mm Hg inclusive at baseline ) despite a variety of antihypertensive medications including diuretics , calcium antagonists , angiotensin converting enzyme ( ACE ) inhibitors , and alpha- or beta-blockers , either singly or in combination . The mean baseline blood pressure for the HBP group was 156/97 mm Hg . C and esartan cilexetil as monotherapy ( in 51 % of HBP patients ) reduced mean SBP/DBP by 18.7/ 13.1 mm Hg . As add-on therapy ( in 49 % of HBP patients ) to various background therapies , c and esartan cilexetil consistently reduced mean SBP/DBP further , irrespective of the background therapy : diuretics ( 17.8/11.3 mm Hg ) , calcium antagonists ( 16.6/11.2 mm Hg ) , beta-blockers ( 16.5/ 10.4 mm Hg ) , ACE inhibitors ( 15.3/10.0 mm Hg ) , alpha-blockers ( 16.4/10.4 mm Hg ) . The mean baseline blood pressure for the ISH group was 158/81 mm Hg . C and esartan cilexetil , as monotherapy ( in 34 % of ISH patients ) , reduced SBP/DBP by 17.0/4.4 mm Hg . As add-on therapy ( in 66 % of ISH patients ) to various background therapies , c and esartan cilexetil consistently reduced mean SBP/DBP further , irrespective of the background therapy : diuretics ( 17.4/5.1 mm Hg ) , calcium antagonists ( 15.6/3.6 mm Hg ) , beta-blockers ( 14.0/4.8 mm Hg ) , ACE inhibitors ( 13.4/4.3 mm Hg ) , and alpha-blockers ( 11.6/4.5 mm Hg ) . The further blood pressure lowering effects of c and esartan cilexetil as add-on therapy were seen regardless of age , sex , and race . Overall , 6.8 % of the 6465 patients withdrew because of adverse events , most commonly headache ( 6.3 % ) and dizziness ( 5.0 % ) . Orthostatic hypotension was infrequent ; 0.2 % with c and esartan cilexetil alone , and 0.8 % with c and esartan cilexetil as add-on therapy . Thus , c and esartan cilexetil either alone or as add-on therapy was highly effective for the control of systolic or diastolic hypertension regardless of demographic background when used in typical clinical practice setting The primary results of a three-year prospect i ve , double-blind , placebo-controlled trial in non-insulin-dependent diabetic ( NIDDM ) patients show that an anti-hypertensive regimen , which includes the ACE inhibitor enalapril , preserves renal function to a greater extent than therapy with antihypertensive agents excluding ACE inhibitors ( J Am Soc Nephrol 3:335 , 1992 ) . The influence of baseline urinary albumin excretion on the renal protective effects of enalapril treatment in these subjects was the objective of this further analysis . Adequate data were available in 121 patients of the 165 hypertensive NIDDM individuals studied [ baseline glomerular filtration rate ( GFR ) 30 to 100 ml/min/1.73 m2 ] . Twenty-four hour urinary excretion of albumin ( UAE ) , protein , urea nitrogen , creatinine and isotopically determined GFR were measured at baseline and six month intervals . Glycemic control and blood pressure regulation were assessed every three months . The rate of loss of GFR was significantly greater in patients with overt proteinuria at baseline ( UAE > 300 mg/24 hr ) as compared to patients with baseline sub- clinical proteinuria ( UAE < or = 300 mg/24 hr ) . Antihypertensive treatment with enalapril  preserved GFR significantly better ( P < 0.01 ) in the patients with sub- clinical proteinuria at baseline ( UAE < or = 300 mg/24 hr ) than other antihypertensive treatments which excluded the ACE inhibitor . Furthermore , only 7 % of the enalapril-treated group progressed to clinical albuminuria compared to 21 % of control treated patients . Although the enalapril-treated group had a lower mean blood pressure during the maintenance period , no correlation between blood pressure ( systolic , diastolic or mean arterial ) and rate of change of GFR was observed . ( ABSTRACT TRUNCATED AT 250 WORDS Angiotensin converting enzyme inhibitors ( ACE-Is ) and angiotensin II receptor blockers ( ARBs ) are frequently used for the treatment for glomerulonephritis and diabetic nephropathy because of their albuminuria- or proteinuria-reducing effects . To many patients who are nonresponsive to monotherapy with these agents , combination therapy appears to be a good treatment option . In the present study , we examined the effects of the addition of an ARB ( losartan ) followed by titration upon addition and at 3 and 6 months ( n=14 ) and the addition of an ACE-I followed by titration upon addition and at 3 and 6 months ( n=20 ) to the drug regimen treatment protocol in type 2 diabetic patients with nephropathy for whom more than 3-month administration of an ACE-I or the combination of an ACE-I plus a conventional antihypertensive was ineffective to achieve a blood pressure ( BP ) of 130/80 mmHg and to reduce urinary albumin to < 30 mg/day . During the 12-month treatment , addition of losartan or addition of an ACE-I to the treatment protocol reduced systolic blood pressure ( SBP ) by 10 % and 12 % , diastolic blood pressure ( DBP ) by 7 % and 4 % , and urinary albumin excretion by 38 % and 20 % of the baseline value , respectively . However , the effects on both BP and urinary albumin were not significantly different between the two therapies . In conclusion , addition of losartan or an ACE-I to an ongoing treatment with an ACE-I , or addition of an ACE-I to ongoing treatment with a conventional antihypertensive were equally effective at reducing the urinary albumin excretion and BP , and provided renal protection in patients with type-2 diabetic nephropathy BACKGROUND Albuminuria and hypertension are predictors of poor renal and cardiovascular outcome in diabetic patients . We tested whether dual blockade of the renin-angiotensin system ( RAS ) with both an angiotensin-converting enzyme ( ACE ) inhibitor and an angiotensin II receptor blocker ( ARB ) is superior to maximal recommended dose of ACE inhibitor in type 1 diabetic patients with diabetic nephropathy ( DN ) . METHODS We performed a r and omized , double-blind , crossover trial with 8 weeks treatment with placebo and irbesartan 300 mg ( once daily ) , added on top of enalapril 40 mg ( once daily ) . We included 24 type 1 patients with DN . At the end of each treatment period , albuminuria , 24-hour blood pressure , and glomerular filtration rate ( GFR ) were measured . RESULTS Values on ACE inhibitors + placebo were : albuminuria [ mean ( 95 % CI ) ] , 519 ( 342 to 789 ) mg/24 hours ; blood pressure [ mean ( SEM ) ] , 131 (3)/74 ( 1 ) mm Hg , and GFR [ mean ( SEM ) ] , 65 ( 5 ) mL/min/1.73 m2 . Dual blockade of the RAS induced a reduction in albuminuria [ mean ( 95 % CI ) ] of 25 % ( 15 , 34 ) ( P < 0.001 ) , a reduction in systolic blood pressure of 8 mm Hg ( 4 , 12 ) ( P = 0.002 ) , and a reduction of 4 mm Hg ( 2 , 7 ) ( P = 0.003 ) in diastolic blood pressure . GFR and plasma potassium remained unchanged during both treatment regimes . Dual blockade was safe and well tolerated . CONCLUSION Dual blockade of the RAS is superior to maximal recommended dose of ACE inhibitors with regard to lowering of albuminuria and blood pressure in type 1 patients with DN . Long-term trials are needed to further establish the role of dual blockade of the RAS in renal and cardiovascular protection Objective This prospect i ve , r and omised , open-label , blinded-endpoint study was to compare the effects of the angiotensin II ( Ang II ) AT1 receptor antagonist valsartan with those of the ACE inhibitor enalapril on blood pressure ( BP ) and cognitive functions in elderly hypertensive patients . Methods One hundred and forty-four patients aged 61–80 years with mild to moderate essential hypertension ( DBP ≥95 mmHg and ≤110 mmHg at the end of a 2-week placebo run-in period ) were r and omly assigned to once daily ( o.d . ) treatment with valsartan 160 mg ( n=73 ) or enalapril 20 mg ( n=71 ) for 16 weeks . The patients were examined every 4 weeks during the study , with pre-dose BP ( st and ard mercury sphygmomanometer , Korotkoff I and V ) and heart rate ( pulse palpation ) being recorded at each visit . Cognitive function was evaluated at the end of the wash-out period and after 16 weeks of active treatment by means of five tests ( verbal fluency , the Boston naming test , word list memory , word list recall and word list recognition ) . Results Both valsartan and enalapril had a clear antihypertensive effect , but the former led to a slightly greater reduction in SBP/DBP at 16 weeks ( 18.6±4.6/13.7±4.0 mmHg vs 15.6±5.1/10.9±3.9 mmHg ; P<0.01 ) . Enalapril did not induce any significant changes in any of the cognitive function test scores  ; valsartan significantly increased the word list memory score ( + 11.8 % ; P<0.05 vs baseline and P<0.01 vs enalapril ) and the word list recall score ( + 18.7 % ; P<0.05 vs baseline and P<0.01 vs enalapril ) , but not those of the other tests . Conclusion These findings indicate that , in elderly hypertensive patients , 16 weeks of treatment with valsartan 160 mg o.d . is more effective than enalapril 20 mg o.d . in reducing BP , and ( unlike enalapril ) improves some of the components of cognitive function , particularly episodic memory Two first‐line antihypertensive therapies for initiating treatment in hypertension were compared , the angiotensin‐converting enzyme inhibitor ( ACEI ) zofenopril and the beta‐blocker atenolol . The study was multi‐centre and double‐blind , and included 304 middle‐aged to elderly patients with mild to moderate hypertension who were r and omized to receive either zofenopril 30–60 mg once daily ( od ) or atenolol 50–100 mg od for 4 weeks with the possibility to an up‐titration in non‐responding patients . The higher dose level was then administered until 12 weeks after r and omization . Blood pressures ( BPs ) were substantially reduced by either treatment , but after 4 weeks , the systolic and diastolic BP reductions were significantly greater ( p<0.05 ) with zofenopril ( −15.6/−13.5 mmHg ) compared with atenolol ( −13.1/−11.8 mmHg ) . After 12 weeks and the possibility of dose up‐titration , BP differences between treatments were no longer significant . However , control rates ( sitting diastolic BP < 90 mmHg ) for zofenopril remained significantly higher compared with atenolol .  The number of subjects with adverse drug reactions possibly or probably related to the study medication was 14 ( 9.1 % ) in the zofenopril group and 30 ( 20.8 % ) in the atenolol group ( p = 0.008 ) . It is concluded that zofenopril as well as atenolol induces substantial reductions of diastolic BP in middle‐aged to elderly patients with hypertension . However , the control rate when initiating antihypertensive therapy with zofenopril is higher than that for atenolol The aim of this study was to compare the effects of tr and olapril and losartan on plasminogen activator inhibitor type 1 ( PAI-1 ) levels and insulin sensitivity in hypertensive postmenopausal women . We studied 89 hypertensive ( diastolic blood pressure > 90 and < 110 mm Hg ) postmenopausal women , aged 51 to 60 years not taking any hormone replacement therapy . Diabetic , obese , and smoking patients were excluded . After a 4-week placebo period , they were r and omized to receive 2 mg of oral tr and olapril ( n=45 ) or 50 mg of oral losartan ( n=44 ) for 12 weeks according to a double-blind , parallel group design . At the end of the placebo and active treatment periods , blood pressure ( BP ) was measured , plasma sample s were drawn to evaluate PAI-1 antigen levels , and insulin sensitivity was assessed . Both tr and olapril and losartan reduced systolic BP ( by a mean of 16.9 mm Hg and 15.2 mm Hg , respectively , P < .01 v placebo ) and diastolic BP ( by a mean of 13.1 mm Hg and 11.9 mm Hg , respectively , P < .01 v placebo ) with no difference between the two treatments . The PAI-1 antigen levels were significantly decreased by tr and olapril ( from 36.9+/-21 ng/dL to 27.2+/-17 ng/dL , P < .05 ) , but not by losartan ( from 35.3+/-22 ng/dL to 37.1+/-23 ng/dL , P = not significant ) . Glucose infusion rate was significantly increased by tr and olapril ( from 6.67+/-0.56 mg/min/kg to 7.9+/-0.65 mg/min/kg , P < .05 ) , but was not significantly modified by losartan ( from 6.7+/-0.47 mg/min/kg to 6.9+/-0.50 mg/min/kg , P= not significant ) . In the tr and olapril group the PAI-1 decrease correlated with glucose infusion rate increase ( r=0.36 , P=.045 ) These results provide evidence of different effects of angiotensin converting enzyme inhibitors and AT1 antagonists on fibrinolysis and suggest that the PAI-1 decrease induced by angiotensin converting enzyme inhibitors is related to their action on insulin sensitivity and is not dependent on angiotensin II antagonism but rather on other mechanisms . It remains to be seen whether these findings apply to other patient population s than postmenopausal women Pharmacologic studies in hypertension often describe blood pressure ( BP ) reductions in placebo control groups . This placebo effect is currently debated , as it seems to be related to BP measurement methods and as a regression to the mean phenomenon may lead to misinterpretation . Furthermore , data on pulse pressure are lacking . This study was design ed to evaluate the placebo effect on BP and to differentiate it from regression to the mean . According to a crossover design , 26 mild-to-moderate hypertensive patients who were treated with placebo or given no treatment  were followed-up for 1 month . Clinic and ambulatory BP was assessed at baseline and at the end of each 1-month period . Placebo administration result ed in significant reductions in clinic systolic , diastolic , and mean BP ( P < .01 ) , ambulatory 24-h SBP ( P < .05 ) , and daytime systolic , diastolic , and mean BP ( P < .01 , P < .05 , P < .01 , respectively ) . No significant differences were noted for pulse pressure and heart rate or between BP values measured at baseline and after 1 month without treatment . Despite a significant correlation between changes in clinic and ambulatory BP , the scatter of individual data suggests that the placebo response observed with one method can not be systematic ally extrapolated to the other method . This study conclusively shows the effect of placebo in mild-to-moderate hypertension on both clinic and ambulatory systolic , diastolic , and mean BP , in which it has been shown to differ from the regression to the mean phenomenon . This effect was not observed for pulse pressure or heart rate BACKGROUND Despite widespread use in hypertensive children , the safety and effectiveness of lisinopril had not been previously tested in a controlled study . METHODS This study explored the dose-response relationship and safety of lisinopril in 115 hypertensive children , aged 6 to 16 years . Patients were r and omized in a double-blind fashion for 2 weeks to one of three doses by body weight at baseline : < 50 kg : low ( 0.625 mg ) , middle ( 2.5 mg ) , high ( 20 mg ) , and > or = 50 kg : low ( 1.25 mg ) , middle ( 5 mg ) , high ( 40 mg ) . The dose-response for lisinopril was evaluated by analyzing the change in slope in sitting diastolic and systolic blood pressure ( BP ) by dose after 2 weeks of therapy compared to baseline . Patients then entered a double-blind withdrawal , where patients were either switched to placebo or continued their current lisinopril treatment for up to 2 weeks . Patients completed period II when their BP returned to baseline . Antihypertensive effectiveness , between placebo and lisinopril was determined for all doses . Adverse events were carefully monitored . RESULTS There was a dose-response relationship between the lowest and each of the higher doses of lisinopril . Blood pressure in the placebo group increased after withdrawal of lisinopril . The dose-response relationship was consistent across all subgroups ( ie , age , Tanner stage , ethnicity , gender ) . CONCLUSIONS Lisinopril , once daily , is an effective and well-tolerated antihypertensive in children aged 6 to 16 years . An initial dose of 0.07 mg/kg , administered once daily , effectively lowered BP within 2 weeks . Blood pressure was reduced in a dose-dependent fashion Controlled studies have demonstrated that relaxation training can lead to significant in-clinic blood pressure ( BP ) reductions in patients with essential hypertension . We examined the BP-lowering effect of relaxation training during the working day . Forty-two patients being treated for essential hypertension with diastolic BPs greater than 90 mm Hg were r and omized into either a relaxation training program or no treatment .  Multiple BP measurements were made during the working hours , using an ambulatory monitoring device , before and after training . Significant work-site differences between groups were evident after treatment both for systolic and diastolic pressures . These results suggest that relaxation therapy leads to a reduction in BP that is evident in the natural environment , providing new evidence that the procedure is a useful adjunct to the treatment of hypertensive patients Summary : The antihypertensive effect of the angiotensin-converting enzyme ( ACE ) inhibitor lisinopril administered in a single dose of 20 mg was evaluated by ambulatory blood pressure monitoring ( ABPM ) in a double-blind , placebo-controlled , cross-over study . Twenty-four patients ( 21 men and 3 women , mean age 52 ± 6 years ) with mild to moderate hypertension were included in the study and r and omly assigned to two consecutive treatments with lisinopril 20 mg and placebo , each administered for 4 weeks . On the last day of each treatment , BP was assessed by noninvasive 24-h ABPM . BP was significantly lower  after lisinopril than after placebo in a 24-h period ( mean 24-h systolic BP ( SBP )  with lisinopril 120 ± 7 mm Hg and with placebo 135 ± 9 mm Hg ; mean day SBP with lisinopril 125 ± 3 mm Hg and with placebo 142 ± 5 mm Hg ; mean night SBP with lisinopril 112 ± 4 mm Hg and with placebo 124 ± 6 mm Hg ; mean 24-h diastolic BP ( DBP )  with lisinopril 76 ± 6 mm Hg , and with placebo 87 ± 8 mm Hg ; mean day DBP  with lisinopril 80 ± 3 mm Hg and with placebo 93 ± 4 mm Hg ; mean night DBP  with lisinopril 69 ± 2 mm Hg and with placebo 79 ± 5 mm Hg , p < 0.001 ) . Mean 24-h , mean day , and mean night heart rate ( HR ) did not differ significantly between placebo and lisinopril treatments . Repeated- measures analysis of variance ( ANOVA ) showed a significant influence on SBP ( p 0.001 ) and DBP ( p < 0.001 ) throughout the treatment . A significant time effect was also evident both for SBP ( p 0.001 ) and DBP ( p < 0.001 ) . The interaction of time and treatment was not significant , suggesting that the circadian rhythm of BP was not different during the two treatments . No serious side effects were observed during this study The purpose of the present study was to examine the effects of salt-restriction alone and in combination with an angiotensin-converting enzyme ( ACE ) inhibitor ( cilazapril ) on both office and ambulatory blood pressure ( BP ) levels in free living subjects with elevated BP . The study was carried out in an out-patient setting with subjects recruited from occupational health care system mainly . After exclusions , 39 subjects ( 24 men , 15 women , aged 28 - 65 years ) with mildly to moderately elevated BP completed the study . After 3 months run-in period with placebo ( first month on normal-salt and the next 2 months on sodium-restricted diet ) the subjects were r and omised into either salt-restriction placebo or salt-restriction cilazapril ( 2.5 mg daily ) groups for 3 months . In the whole group , 24-h urinary sodium excretion decreased ( mean + /- s.d . ) from 198 + /- 60 to 112 + /- 59 mmol ( 4 weeks vs 24 weeks , P < 0.001 ) . Systolic and diastolic office BP decreased during the placebo-sodium-restriction phase ( -7.1 [ 95 % Cl -11.2 ; -3.0 ] and -4.2 [ 95 % Cl -6.6 ; -1.8 ] mm Hg for systolic and diastolic BP ) , and similarly the daytime ambulatory BP ( ABP ) was reduced during this period ( -2.8 [ 95 % Cl -5.2 ; -0.5 ] and -2.8 [ 95 % Cl -4.5 ; -1.2 ] mm Hg , systolic ( SBP ) and diastolic blood pressure ( DBP ) respectively ) . No changes were observed in the night time ABP . Addition of cilazapril to sodium-restriction enhanced significantly the office BP ( -13.2 , [ 95 % Cl -20.2 ; -6.2 ] , and -9.1 [ 95 % Cl -13.5 ; -4.7 ] ) and daytime ABP ( -5.9 , [ 95 % Cl -10.1 ; -1.8 ] and -5.3 , [ 95 % Cl -8.8 ; -1.9 ] ) reduction . Blood glucose , plasma insulin or serum lipids did not change during the study . Moderate sodium restriction seems to lower the office and daytime ABP levels in subjects with mild-to-moderate hypertension . The antihypertensive effect of cilazapril could be enhanced by sodium restriction BACKGROUND By blocking the renin-angiotensin-aldosterone system ( RAAS ) at its rate-limiting step , renin inhibition may provide improved RAAS suppression . We investigated the blood pressure (BP)-lowering effects of the oral direct renin inhibitor aliskiren , alone or in combination with the angiotensin receptor blocker valsartan . METHODS In this multicenter , r and omized , placebo-controlled , 8-week trial , 1123 patients with mild-to-moderate hypertension underwent a 3 to 4 week single-blind placebo run-in and were then r and omized in a modified factorial study design to receive once-daily , double-blind oral treatment with placebo , aliskiren monotherapy ( 75 , 150 , or 300 mg ) , valsartan monotherapy ( 80 , 160 , or 320 mg ) , aliskiren and valsartan in combination , or valsartan/hydrochlorothiazide ( 160/12.5 mg ) . The primary efficacy variable was the change from baseline in mean sitting diastolic BP ( DBP ) at endpoint . RESULTS Once-daily oral treatment with aliskiren 300 mg significantly ( P < .0001 ) lowered mean sitting DBP and systolic BP ( SBP ) compared with placebo ; aliskiren monotherapy demonstrated a safety and tolerability profile comparable to placebo . Changes in DBP and SBP were fitted to a first-order dose-response surface ( lack-of-fit test , P = .65 ) , which showed that aliskiren and valsartan alone and in combination produced dose-related reductions in DBP and SBP . Coadministration of aliskiren and valsartan produced a greater antihypertensive effect than either drug alone , comparable in magnitude to the effect of valsartan/hydrochlorothiazide , with similar tolerability to the component monotherapies and to placebo . CONCLUSIONS Aliskiren monotherapy provides antihypertensive efficacy and placebo-like tolerability in patients with hypertension .  Aliskiren and valsartan in combination may provide additive BP-lowering effects with maintained tolerability BACKGROUND Local pulse pressure ( PP ) is an independent determinant of carotid artery wall thickness , stronger than mean blood pressure ( BP ) . The present study was design ed to assess whether a beta-adrenoceptor antagonist-based or an ACE inhibitor-based treatment was able to reduce carotid artery wall hypertrophy through a reduction in carotid PP rather than by lowering mean BP and whether the influence of local PP reduction could also be detected at the site of a muscular artery , the radial artery . METHODS AND RESULTS Ninety-eight essential hypertensive patients were r and omized to 9 months of double-blind treatment with either celiprolol or enalapril . Arterial parameters were determined with high-resolution echo-tracking systems . PP was measured locally with applanation tonometry and independently of mean BP . After 9 months of treatment , mean BP , carotid PP , and intimal-medial thickness ( IMT ) decreased significantly , with no difference between the 2 groups . The reduction in carotid PP but not in mean BP was a major independent determinant of the reduction in carotid IMT . Radial artery IMT and PP decreased significantly with both treatments . However , the reduction in radial artery IMT was not related to the changes in radial artery PP . CONCLUSIONS The regression of carotid artery wall hypertrophy during long-term antihypertensive treatment was dependent on the reduction in local PP rather than on the lowering of mean BP . The effect of PP lowering on IMT reduction was observed at the site of an elastic artery but not at the site of a muscular artery Evaluation of safety and efficacy of new drugs is based largely on data from clinical trials involving a limited number of patients . This approach does not necessarily detect the rare adverse events that may only be observed when very large numbers of patients are studied . Consequently , we design ed a double-blind 12-week trial comparing the new angiotensin-converting enzyme ( ACE ) inhibitor , quinapril ( n = 5,053 ) , with a well-established beta-adrenergic receptor blocker , metoprolol  ( n = 506 ) . Essentially hypertensive patients ( diastolic blood pressure 95 - 114 mm Hg ) received either 10 mg quinapril or 50 mg metoprolol once daily , and the doses were doubled at 4-week intervals to a maximum of 40 and 200 mg , respectively , in nonresponders . Responder rates were similar under both regimens . Adverse events were assessed by interview as well as by a st and ard question naire . The overall prevalence of adverse events reported by st and ard question naire was higher than that reported spontaneously during interviews . With respect to typical ACE inhibitor adverse reactions ( e.g. cough and taste disturbances ) , there was no difference between quinapril and metoprolol independent of the mode of reporting . In summary , both drugs showed comparable overall tolerance and safety . The discrepancy between spontaneously reported and question naire-reported adverse events was noteworthy , and this finding prevailed in a volunteer group of 327 patients who were treated with quinapril for 52 weeks . Thus , a question naire is of great significance in addition to the patient history/interview in a large-scale , double-blind study design ed to learn about details of drug safety In the present study , we evaluated the effect of a nonevaluative social support intervention ( pet ownership ) on blood pressure response to mental stress before and during  ACE inhibitor therapy . Forty-eight hypertensive individuals participated in an experiment at home and in the physician ’s office . Participants were r and omized to an experimental group with assignment of pet ownership in addition to lisinopril ( 20 mg/d ) or to a control group with only lisinopril ( 20 mg/d ) . On each study day , blood pressure , heart rate , and plasma renin activity were recorded at baseline and after each mental stressor ( serial subtraction and speech ) . Before drug therapy , mean responses to mental stress did not differ significantly between experimental and control groups in heart rate ( 94 [ SD 6.8 ] versus 93 [ 6.8 ] bpm ) , systolic blood pressure ( 182 [ 8.0 ] versus 181 [ 8.3 ] mm Hg ) , diastolic blood pressure ( 120 [ 6.6 ] versus 119 [ 7.9 ] mm Hg ) , or plasma renin activity ( 9.4 [ 0.59 ] versus 9.3 [ 0.57 ] ng · mL−1 · h−1 ) . Lisinopril therapy lowered resting blood pressure by ≈35/20 mm Hg in both groups , but responses to mental stress were significantly lower among pet owners relative to those who only received lisinopril ( P < 0.0001 ; heart rate 81 [ 6.3 ] versus 91 [ 6.5 ] bpm , systolic blood pressure 131 [ 6.8 ] versus 141 [ 7.8 ] mm Hg , diastolic blood pressure 92 [ 6.3 ] versus 100 [ 6.8 ] mm Hg , and plasma renin activity 13.9 [ 0.92 ] versus 16.1 [ 0.58 ] ng · mL−1 · h−1 ) . We conclude that ACE inhibitor therapy alone lowers resting blood pressure , whereas increased social support through pet ownership lowers blood pressure response to mental stress This study was design ed to investigate the efficacy of Qigong as a non-pharmacological treatment of hypertension and evaluate the contribution of Qigong in the blood pressure ( BP ) reduction of essential hypertension patients . Fifty-eight patients volunteered to participate in this study and were r and omly divided into either a Qigong group ( n = 29 ) , or a wait list control group ( n = 29 ) . In response to 10 weeks of Qigong , systolic blood pressure ( SBP ) , diastolic blood pressure ( DBP ) , and rate pressure product ( RPP ) were decreased significantly . There was a significant reduction of norepinephrine , epinephrine , cortisol , and stress level by the Qigong . These results suggest that Qigong may reduce BP and catecholamines via stabilizing the sympathetic nervous system . Therefore , Qigong is an effective nonpharmacological modality to reduce BP in essential hypertensive Background —Loss of negative feedback inhibition of renin release during chronic treatment with an angiotensin-converting enzyme ( ACE ) inhibitor leads to a compensatory rise in renin secretion and downstream components of the renin-angiotensin-aldosterone ( RAAS ) cascade . This may overcome ACE inhibition but should be blocked by a direct renin inhibitor . We studied the effects of adding the direct renin inhibitor aliskiren to an ACE inhibitor in patients with heart failure . Methods and Results — Patients with New York Heart Association class II to IV heart failure , current or past history of hypertension , and plasma brain natriuretic peptide ( BNP ) concentration > 100 pg/mL who had been treated with an ACE inhibitor ( or angiotensin receptor blocker ) and β-blocker were r and omized to 3 months of treatment with placebo  ( n=146 ) or aliskiren 150 mg/d ( n=156 ) . The primary efficacy outcome was the between-treatment difference in N-terminal pro-BNP ( NT-proBNP ) . Patients ’ mean age was 68 years , mean ejection fraction was 31 % , and mean±SD systolic blood pressure was 129±17.4 mm Hg . Sixty-two percent of the patients were in New York Heart Association functional class II , and 33 % were taking an aldosterone antagonist . Plasma NT-proBNP rose by 762±6123 pg/mL with placebo and fell by 244±2025 pg/mL with aliskiren  ( P=0.0106 ) . BNP and urinary ( but not plasma ) aldosterone were also reduced by aliskiren . Clinical ly important differences in blood pressure and biochemistry were not seen between aliskiren and placebo . Conclusions —Addition of aliskiren to an ACE inhibitor ( or angiotensin receptor blocker ) and β-blocker had favorable neurohumoral effects in heart failure and appeared to be well tolerated Objective To compare the antihypertensive efficacy and systemic tolerability of valsartan , a new angiotensin II receptor antagonist , with placebo and with an angiotensin converting enzyme ( ACE ) inhibitor , enalapril . Design A total of 348 adult out patients with mild-to-moderate uncomplicated essential hypertension participated in this double-blind , parallel , study . Patients were allocated r and omly in a ratio of 2:2:1 to receive 80 mg valsartan once a day , 20 mg enalapril once a day , or placebo for 8 weeks in general practice . Patients were assessed at 4 and 8 weeks of therapy . Main outcome measures The primary efficacy variable was the change from baseline in mean sitting diastolic blood pressure ( SDBP ) after 8 weeks of therapy . Secondary variables included the change in sitting systolic blood pressure ( SSBP ) and response rates at 8 weeks . Results Valsartan and enalapril produced statistically significant reductions in diastolic and systolic blood pressures compared with placebo . Similar falls were found in both of the active treatment groups with mean changes in SDBP at 8 weeks of — 9.5mmHg for valsartan and — 9.4mmHg for enalapril ( 4.5mmHg for placebo ) . No significant differences between valsartan and enalapril were found for reductions in SDBP or SSBP . Response rates at 8 weeks were significantly greater for valsartan ( 54 % ) and enalapril ( 58 % ) than for placebo ( 20 % ) , with no significant difference between the two active treatments . Both valsartan and enalapril demonstrated a consistent a nti hypertensive effect over time , with 90 % of patients with a response at 4 weeks responding at 8 weeks . Both of the treatments were tolerated well . Although the incidence of coughing was generally low in the study , more cases were reported with enalapril ( three ) than with valsartan ( one ) or placebo ( none ) . Conclusions The data show 80 mg valsartan once a day to be as effective as 20 mg enalapril once a day in the treatment of mild-to-moderate hypertension . Valsartan is tolerated well and does not appear to be associated with any increase in the incidence of coughing BACKGROUND The objective of this study was to compare the antihypertensive efficacy and tolerability of c and esartan cilexetil ( CC ) with that of enalapril ( E ) and placebo ( P ) in hypertensives by clinic and ambulatory blood pressure ( BP ) .  PROCEDURES The study was an Italian multicenter , r and omized , double-blind , parallel group trial including 227 mild to moderate essential hypertensives ( age range , 18 to 70 years ) . After 4 weeks of P , patients were r and omized to 8 weeks of treatment with P or CC ( 4 mg ) or E ( 10 mg ) once daily , which was eventually increased to 8 mg and 20 mg once daily in nonresponders . At the end of each study phase , trough BP was measured by conventional sphygmomanometry and ambulatory BP was monitored over 24 h by a Spacelabs device . Analysis of 24-h BP profile included calculation of 24-h , daytime , nighttime , and hourly average values . RESULTS In the 178 patients evaluable per protocol , at the end of 8 weeks of treatment , trough systolic ( S ) and diastolic ( D ) BP were similarly reduced by both active treatments ( 13 + /- 12 and 10 + /- 7 mm Hg for CC and 14 + /- 12 and 10 + /- 7 mm Hg for E ) and significantly more by both treatments than by P ( 6 + /- 11 and 7 + /- 8 mm Hg , P < .01 v CC and E ) . In the 85 patients with valid 24-h recordings reduction in 24-h BP was again similar for the two active groups . The antihypertensive effect was still evident during h 23 and 24 after the last dose for both active treatments ( 8 + /- 20 v 5 + /- 18 mm Hg for SBP and 4 + /- 12 v 6 + /- 13 mm Hg for DBP , CC v E , respectively ) but not for P. Heart rate was not significantly modified by either active treatment . The incidence of adverse events was greater in the E than in the CC group . CONCLUSIONS Our study provides evidence that CC at a dose of 4 to 8 mg is as effective as E at a dose of 10 to 20 mg over 24 h , but is better tolerated than Background Inhibition of the angiotensin I-converting enzyme ( ACE ) is a widely used principle for the treatment of hypertension . Fermentation of milk proteins was shown to lead to the formation of peptides with ACE-inhibiting activity . Milk products with ACE-inhibiting peptides may provide a useful approach to prevent or treat hypertension . Aim of the study To investigate the effect of a milk drink supplemented with whey peptides on blood pressure in mildly hypertensive subjects . Methods A r and omized , placebo-controlled , double blind clinical trial in two parallel groups was performed . A total of 54 hypertensive patients received either 125 ml of a milk drink supplemented with whey peptides every morning or a control product for 12 weeks after a run-in period of 2 weeks . Previous in vitro tests of the whey powder demonstrated ACE-inhibitory activity . Blood pressure was measured at 0 , 2 , 4 , 8 , and 12 weeks . Fasting blood sample s were collected at 0 , 4 , 8 , and 12 weeks for analysis of metabolic and inflammatory variables . Results Resting systolic and diastolic blood pressure values did not change in the milk drink group 144.1 ± 8.6/91.0 ± 5.5 mmHg at baseline vs. 143.7 ± 13.5/90.4 ± 6.5 mmHg after 12 weeks . In the control group systolic ( p = 0.0431 ) and diastolic ( p = 0.0081 ) blood pressure was significantly reduced 140.6 ± 11.7/90.3 ± 5.8 mmHg at baseline vs. 137.0 ± 14.4/87.7 ± 6.6 mmHg after 12 weeks . There was no difference between the two groups at any time point . No changes were seen when the results of the 24-h continuous blood pressure monitoring were compared after 12 weeks . No significant changes were detected for circulating levels of selected inflammation markers ( interleukin (IL)-6 , C-reactive protein ( CRP ) , number of leukocytes , and plasminogen activator inhibitor-1 ( PAI-1 ) as well as for metabolic variables ( insulin , plasma glucose , and lipids ) . Conclusions The daily consumption of 125 ml of a milk drink supplemented with whey peptides was not found to reduce blood pressure and /or inflammation markers in mildly hypertensive subjects , although preceding in vitro tests showed a potent ACE-inhibition The long-term efficacy and tolerance of spironolactone in essential hypertension was evaluated among 20,812 patients referred to the Broussais and St. Joseph systemic hypertension clinics between 1976 and 1985 by using information prospect ively collected in the computerized ARTEMIS data bank . In 182 patients ( 51 men , 131 women ) treated with spironolactone alone  during a mean follow-up period of 23 months , a mean dose of 96.5 mg decreased systolic and diastolic blood pressure ( BP ) by 18 and 10 mm Hg , respectively , below pretherapeutic levels . The BP decrease was greater with doses of 75 to 100 mg ( 12.4 % and 12.2 % ) than with doses of 25 to 50 mg ( 5.3 and 6.5 % , p less than 0.001 ) , but no additional decrease was found with doses above 150 mg . Plasma creatinine level increased modestly ( 8.3 mumol/liters ) , as did plasma potassium level ( 0.6 mmol/liters ) ( both p less than 0.001 ) ; uric acid level increased , but not significantly ( 10.5 mumol/liter ) . Fasting blood glucose and total cholesterol levels did not change , triglyceride levels increased slightly ( 0.1 mmol/liter , p less than 0.05 ) . These changes were similar in both sexes and were not influenced by length of follow-up . Among the 699 men prescribed spironolactone alone or in association with another antihypertensive treatment , 91 cases of gynecomastia developed ( 13 % ) . Gynecomastia was reversible and dose-related ; at doses of 50 mg or less the incidence was 6.9 % , but 52.2 % for doses of 150 mg or higher . Despite limitations inherent in the interpretation of data banks , it is concluded that spironolactone administered in daily practice reduced BP without inducing adverse metabolic adverse effects and that in patients with essential hypertension , doses should be kept below 100 mg Objective The combination of an angiotensin-converting enzyme ( ACE ) inhibitor and an angiotensin II ( Ang II ) receptor antagonist ( ARB ) could provide a higher degree of blockade of the renin-angiotensin system(RAS ) than either agent alone . The primary aim of this study was to look at the effect of three therapeutic regimens ( titrated ACE inhibitor ( ACE-I ) versus titrated ARB versus the combination of an ACE-I and an ARB ) on the attainment of adequate blood pressure ( BP ) control and antiproteinuric effect . Both ACE-I and ARB were titrated as monotherapy up to the maximal recommended dose . Methods A pilot r and omised , parallel group open-label study was conducted in 36 patients with primary renal disease , proteinuria above 1.5 g/day and BP > 140/90 mmHg while on therapy with an ACE-I.  Patients were r and omly assigned to ( 1 ) benazepril , n=12 ; ( 2 ) valsartan , n=12 ; or ( 3 ) benazepril plus valsartan , n=12 . Other antihypertensive therapies could also be added to attain goal BP ( < 140/90 mmHg ) . The primary endpoint was the change in proteinuria during six months of follow-up . Results In the presence of similar BP decreases and stable creatinine clearance values , mean proteinuria decreases were 0.5±1.7 , 1.2±2.0 and 2.5±1.8 g/day in groups 1 , 2 and 3 , respectively . When compared with baseline values , only the fall induced by the combination of ARB and ACE-I attained statistical significance ( p<0.05 ) . Conclusion The antiproteinuric capacity of monotherapy at recommended doses with either an ACE-I or an ARB is lower than that obtained with the combination of the two drugs OBJECTIVE To evaluate the effect on cardiac hemodynamic parameters of valsartan in patients with chronic stable congestive heart failure previously untreated with ACE inhibitors . METHODS After a 2 to 4 week run-in period , 116 adult out patients were r and omized to receive valsartan 40 , 80 or 160 mg twice daily , the ACE inhibitor lisinopril 5/10 mg once daily , or placebo . At baseline and after 28 days of treatment , cardiac hemodynamic parameters were measured . Tolerability was assessed by adverse events and by any changes in systolic or diastolic blood pressure , body weight , heart rate , and routine laboratory parameters . RESULTS For the 12 hour time point ( trough ) , all doses of valsartan reduced mean pulmonary capillary wedge pressure ( statistically significant for valsartan 40 mg and 160 mg ) , decreased systemic vascular resistance ( statistically significant for all three valsartan doses and for lisinopril at peak and trough ) , and increased cardiac output ( statistically significant for all three valsartan doses at peak , and for 80 and 160 mg at trough ) . There were no clinical ly relevant effects on any safety parameters . CONCLUSIONS Valsartan has beneficial effects on cardiac hemodynamics , and is generally well tolerated in patients with congestive heart failure not taking ACE inhibitors The reduction in blood pressure ( BP ) after the first dose and after 8 weeks of treatment with a new once-daily angiotensin converting enzyme ( ACE ) inhibitor , ramipril , was examined in 12 untreated hypertensive patients , using ambulatory intraarterial BP monitoring . The first period of monitoring began 24 hours before the first dose was given , and continued for 24 hours afterwards . A second 24-hour period of monitoring was carried out after 8 weeks of treatment , commencing immediately after the morning dose .  Angiotensin II levels and serum drug levels were measured at 0 , 2 , 6 and 24 hours after the acute dose .  BP decreased progressively from the first hour after the first dose , reached a maximum in the fifth hour ( p less than 0.001 ) and then the effect diminished . The maximum reduction of systolic BP in any patient was 64 mm Hg , the minimum 4 mm Hg . Blood pressure was significantly ( p less than 0.05 ) reduced throughout the 24 hours after dosing , with a mean daytime reduction of 13/12 mm Hg , and a mean nighttime reduction of 15/7 mm Hg . Angiotensin II levels were significantly ( p less than 0.02 ) and maximally reduced by 2 hours after administration , but the reduction was no longer significant after 24 hours . Serum drug levels were also maximal 2 hours after administration . The trial population could be clearly divided into groups of good and poor responders on the basis of BP reduction . The angiotensin II levels were higher before treatment , and decreased further , in all patients with a good response than in those with a poor response . ( ABSTRACT TRUNCATED AT 250 WORDS BACKGROUND Midodrine hydrochloride is the only drug demonstrated in a placebo-controlled treatment trial to improve orthostatic hypotension ( OH ) but it significantly worsens supine hypertension . By enhancing ganglionic transmission , pyridostigmine bromide can potentially ameliorate OH without worsening supine hypertension . OBJECTIVE To evaluate the efficacy of a single 60-mg dose of pyridostigmine bromide , alone or in combination with a subthreshold ( 2.5 mg ) or suprathreshold ( 5 mg ) dose of midodrine hydrochloride , compared with placebo . DESIGN We report a double-blind , r and omized , 4-way cross-over study of pyridostigmine in the treatment of neurogenic OH . A total of 58 patients with neurogenic OH were enrolled . After 1 day of baseline measurements , patients were given 4 treatments ( 3 active treatments [ 60 mg of pyridostigmine bromide ; 60 mg of pyridostigmine bromide and 2.5 mg of midodrine hydrochloride ; 60 mg of pyridostigmine bromide and 5 mg of midodrine hydrochloride ] and a placebo ) in r and om order on successive days . Blood pressure ( BP ) and heart rate were measured , both supine and st and ing , immediately before treatment and hourly for 6 hours after the treatment was given . RESULTS No significant differences were seen in the supine BP , either systolic ( P = .36 ) or diastolic ( P = .85 ) . In contrast , the primary end point of the fall in st and ing diastolic BP was significantly reduced ( P = .02 ) with treatment . Pairwise comparison showed significant reduction by pyridostigmine alone ( BP fall of 27.6 mm Hg vs 34.0 mm Hg with placebo ; P = .04 ) and pyridostigmine and 5 mg of midodrine hydrochloride ( BP fall of 27.2 mm Hg vs 34.0 mm Hg with placebo ; P = .002 ) . St and ing BP improvement significantly regressed with improvement in OH symptoms . CONCLUSIONS Pyridostigmine significantly improves st and ing BP in patients with OH without worsening supine hypertension . The greatest effect is on diastolic BP , suggesting that the improvement is due to increased total peripheral resistance We compared antihypertensive efficacy and safety of a single administration of equipotent doses of lacidipine versus nifedipine in the hypertensive urgencies . Twenty-nine asymptomatic essential hypertensive patients ( nine men , 20 women ) with a mean age of 55.03+/-11.19 years and baseline diastolic blood pressure ( DBP ) of > or = 120 mm Hg after resting 30 min , not taking antihypertensive drugs for the last 24 h , were r and omized in a single-blind fashion to receive lacidipine , 4 mg ( LCD , 15 patients ) or short-acting nifedipine , 20 mg ( NFD , 14 patients ) in a single dose . Blood pressure ( BP ) and heart rate ( HR ) were taken every 30 min during the first 8 h and every 2 h until 24 h of follow-up . Baseline BP values were similar in the two groups ( LCD , 222.5+/-32.8/124.6+/-8.4 mm Hg vs. NFD , 215.9+/-20.6/128+/-7.7 mm Hg ; p = NS ) . Both drugs promoted a significant reduction of systolic blood pressure ( SBP ; 169.6+/-27.8 vs. 170.6+/-25.3 mm Hg ) and diastolic blood pressure ( DBP ; 104.1+/-16 vs. 102.9+/-12.4 mm Hg ) after 8 h. However , either SBP ( 165+/-27.3 vs. 190.6+/-18.2 mm Hg ; p = 0.008 ) and DBP ( 99.9+/-12.3 vs. 117.2+/-11.4 mm Hg ; p = 0.001 ) were significantly higher in the NFD group after 24-h dosing . Eleven patients in the LCD group had a decrease in BP > 25 % of the baseline value both 8 and 24 h after the dose . Although 10 patients showed the same response in the NFD group 8 h after the dose , only four patients maintained these values at 24 h. One patient treated with NFD had a transient cerebrovascular ischemic attack . No adverse effects were observed in the LCD group . We conclude that the long-acting calcium antagonist lacidipine was more effective than the short-acting nifedipine in both controlling BP and maintaining this BP reduction over 8 h in essential hypertensive patients with acute asymptomatic BP increase Abstract —Inhibition of the first and rate-limiting step of the renin-angiotensin system has long been an elusive therapeutic goal . Aliskiren , the first known representative of a new class of completely nonpeptide , orally active , renin inhibitors , has been shown to inhibit the production of angiotensin I and II in healthy volunteers and to reduce blood pressure ( BP ) in sodium-depleted marmosets . The aim of this r and omized , double-blind , active comparator trial study was to assess the BP-lowering efficacy and safety of aliskiren .  Two hundred twenty-six patients , 21 to 70 years of age , with mild to moderate hypertension , were r and omly assigned to receive 37.5 mg , 75 mg , 150 mg , or 300 mg aliskiren or 100 mg losartan daily for 4 weeks . Dose-dependent reductions in daytime ambulatory systolic pressure ( mean change , mm Hg [ SD of change ] ; −0.4 [ 11.7 ] , −5.3 [ 11.3 ] , −8.0 [ 11.0 ] , and −11.0 [ 11.0 ] , P = 0.0002 ) and in plasma renin activity ( median change % [ interquartile range ] ; −55 [ −64 , −11 ] , −60 [ −82 , −46 ] , −77 [ −86 , −72 ] , and −83 [ −92 , −71 ] , P = 0.0008 ) were observed with 37.5 , 75 , 150 , and 300 mg aliskiren . The change in daytime systolic pressure with 100 mg losartan ( −10.9 [ 13.8 ] ) was not significantly different from the changes seen with 75 , 150 , and 300 mg aliskiren . Aliskiren was well tolerated at all doses studied . This study demonstrates that aliskiren , through inhibition of renin , is an effective and safe orally active BP-lowering agent . Whether renin inhibition results in protection from heart attack , stroke , and nephropathy , similar to angiotensin-converting enzyme inhibition and angiotensin receptor blockade , needs to be research ed BACKGROUND Persistent activation of the renin-angiotensin-aldosterone-system ( RAAS ) is known to occur in patients with chronic heart failure ( CHF ) despite treatment with angiotensin-converting enzyme inhibitor ( ACE ) therapy . When added to ACE inhibitors , angiotensin II type 1 ( AT1 ) antagonists may allow more complete blockade of the RAAS and preserve the beneficial effects of bradykinin accumulation not seen with AT1 receptor blockade alone . METHODS Thirty-six patients with stable New York Heart Association class II-IV CHF receiving ACE inhibitor therapy were r and omly assigned in a double-blind manner to receive either eprosartan , a specific competitive AT1 receptor antagonist ( 400 to 800 mg daily , n = 18 ) or placebo ( n = 18 ) for 8 weeks . The primary outcome measure was left ventricular ejection fraction ( LVEF ) as measured by radionuclide ventriculography  , and secondary measures were central hemodynamics assessed by Swan-Ganz catheterization and neurohormonal effects . RESULTS There was no change in LVEF with eprosartan therapy ( mean relative LVEF percentage change [ SEM ] + 10.5 % [ 9.3 ] vs + 10.1 % [ 5.0 ] , respectively ; difference , 0.4 ; 95 % confidence interval [ CI ] , -20.8 to 21.7 ; P = .97 ) . Eprosartan was associated with a significant reduction in diastolic blood pressure and a trend toward a reduction in systolic blood pressure compared with placebo ( -7.3 mm Hg [ 95 % CI , -14.2 to -0.4 ] diastolic ; -8.9 mm Hg [ 95 % CI , -18.6 to 0.8 ] systolic ) . No significant change in heart rate or central hemodynamics occurred during treatment with eprosartan compared with placebo . A trend toward an increase in plasma renin activity was noted with eprosartan therapy . Eprosartan was well tolerated , with an adverse event profile similar to placebo , whereas kidney function remained unchanged . CONCLUSIONS When added to an ACE inhibitor , eprosartan reduced arterial pressure without increasing heart rate . There was no change in LVEF after 2 months of therapy with eprosartan Introduction Self-management of hypertension , including self-monitoring and antihypertensive medication titration , lowers blood pressure ( BP ) at 1 year compared to usual care . The aim of the current trial is to assess the effectiveness of the Home and Online Management and Evaluation of Blood Pressure ( HOME BP ) intervention for the self-management of hypertension in primary care . Methods and analysis The HOME BP trial will be a r and omised controlled trial comparing BP self-management — consisting of the HOME BP online digital intervention with self-monitoring , lifestyle advice and antihypertensive drug titration — with usual care for people with uncontrolled essential hypertension . Eligible patients will be recruited from primary care and r and omised to usual care or to self-management using HOME BP . The primary outcome will be the difference in mean systolic BP ( mm Hg ) at 12-month follow-up between the intervention and control groups adjusting for baseline BP and covariates . Secondary outcomes ( also adjusted for baseline and covariates where appropriate ) will be differences in mean BP at 6 months and diastolic BP at 12 months ; patient enablement ; quality of life , and economic analyses including all key re sources associated with the intervention and related services , adopting a broad societal perspective to include NHS , social care and patient costs , considered within trial and modelled with a lifetime horizon . Medication beliefs , adherence and changes ; self-efficacy ; perceived side effects and lifestyle changes will be measured for process analyses . Qualitative analyses will explore patient and healthcare professional experiences of HOME BP to gain insights into the factors affecting acceptability , feasibility and adherence . Ethics and dissemination This study has received NHS ethical approval ( REC reference 15/SC/0082 ) . The findings from HOME BP will be disseminated widely through peer- review ed publications , scientific conferences and workshops . If successful , HOME BP will be directly applicable to UK primary care management of hypertension . Trial registration number IS RCT N13790648 ; pre- results ACE2 appears to counterbalance the vasopressor effect of angiotensin I converting enzyme ( ACE ) in the renin‐angiotensin system . We hypothesized that ACE2 polymorphisms could confer a high risk of hypertension and have an impact on the antihypertensive response to ACE inhibitors . The hypothesis was tested in two case‐control studies and a clinical trial of 3,408 untreated hypertensive patients r and omized to Atenolol , Hydrochlorothiazide , Captopril , or Nifedipine treatments for 4 weeks . ACE2 rs2106809 T allele was found to confer a 1.6‐fold risk for hypertension in women ( 95 % confidence interval ( CI ) , 1.13–2.06 ) , whereas when combined with the effect of the ACE DD genotype , the risk was 2.34‐fold ( 95 % CI , 1.75–4.85 ) in two independent sample s. The adjusted diastolic blood pressure response  to Captopril was 3.3 mm Hg lower in ACE2 T allele carriers than in CC genotype carriers ( P=0.019 ) in women . We conclude that the ACE2 T allele confers a high risk for hypertension and reduced antihypertensive response to ACE inhibitors The antihypertensive efficacy and tolerability of a fixed combination of benazepril ( 10 mg ) and low-dose amlodipine ( 2.5 mg ) were assessed in 24 patients ( mean age , 43.9 years ) with uncomplicated mild to moderate essential hypertension [ supine diastolic blood pressure ( DBP ) > or = 95 and < or = 120 mm Hg ) ] . After 2 weeks of washout taking placebo , patients were r and omized to receive the fixed combination or placebo , both administered once daily for 3 weeks , according to a double-blind , crossover design . Patients were checked at the end of the washout period and every 3 weeks thereafter . At each visit , 24-h ambulatory BP monitoring ( ABPM ) was performed by a noninvasive device ( Spacelabs 90207 ) ; casual BP ( by mercury sphygmomanometer ) , heart rate ( HR ) , and body weight also were measured . The fixed combination significantly reduced systolic ( SBP ) and DBP values throughout the 24 h as compared with placebo , without affecting the normal BP circadian variability . The antihypertensive effect of the fixed combination could be observed to a similar extent during the day and night and was still significant 24 h after dosing . HR and body weight were not affected by the treatment . The fixed combination of benazepril 10 mg/amlodipine 2.5 mg was well tolerated , and no patient withdrew from the study because of side effects In 2004–2005 , the antihypertensive effects of telmisartan 80 mg versus valsartan 160 mg combined with hydrochlorothiazide 25 mg were assessed in a large placebo-controlled trial in patients with stages 1 and 2 hypertension and demonstrated that both agents were highly effective in lowering blood pressure ( BP ) compared with placebo and that telmisartan lowered BP significantly greater than valsartan . To confirm this finding according to Food and Drug Administration guidelines , we performed a second large trial using the same design in an entirely separate patient population . The trial was double-blind with a 4 : 4 : 1 r and omization scheme to compare once daily telmisartan 80 mg plus hydrochlorothiazide 25 mg versus once daily valsartan 160 mg plus hydrochlorothiazide 25 mg versus once daily placebo on reductions in seated clinic BP in patients with stages 1 and 2 hypertension . The primary endpoints were the changes from baseline in seated diastolic and systolic BP at the end of the 8-week treatment period . Safety endpoints included adverse events , changes in laboratory parameters and pulse rate . In total , 1185 patients were r and omized ( of which 1181 were treated and included in the primary analysis : 528 in the  telmisartan-hydrochlorothiazide  group , 523 in the valsartan-hydrochlorothiazide group , and 130 in the placebo group ) , changes from baseline in BP  following telmisartan-hydrochlorothiazide ( −24.6/−18.2 mmHg ) were significantly greater than both placebo ( −4.1/−6.1 mmHg ) and valsartan-hydrochlorthiazide ( −22.5/−17.0 mmHg ) ( versus placebo , P<0.0001 for systolic and diastolic BP ; versus valsartan-hydrochlorothiazide , P=0.017 for systolic BP and P=0.025 for diastolic BP ) . The total number of patients with at least one adverse event reported was similar among the three treatment groups ( placebo , 42 % , telmisartan-hydrochlorothiazide , 36 % , and valsartan-hydrochlorothiazide , 37 % ) . Thus , this large , second trial confirms that telmisartan-hydrochlorothiazide at doses of 80/25 mg lowered both systolic and diastolic BP to a greater extent than valsartan-hydrochlorothiazide at doses of 160/25 mg in stages 1–2 hypertension . Although these are not the highest doses of these agents at present , at the time that the studies were conducted , they were the maximally approved dosages . Both studies support the strategy of using angiotensin receptor blockers with a higher dose of a thazide diuretic ( 25 mg ) for enhancing the control of hypertension BACKGROUND Elevated pulse pressure ( PP ) is strongly associated with micro- and macrovascular complications in type 2 diabetic patients . We examined the effect of 12 months of dual blockade with c and esartan and lisinopril vs. high-dose lisinopril monotherapy on ambulatory PP in hypertensive type 2 diabetic patients from the CALM ( C and esartan and Lisinopril Microalbuminuria Trial ) II study . METHODS The CALM II study was a 12-month prospect i ve , r and omized , parallel-group , double-masked study that included 75 type 1 and type 2 diabetic subjects with hypertension . Participants were r and omized for treatment with either high-dose lisinopril ( 40 mg once daily ( o.d . ) ) or for dual blockade treatment with c and esartan ( 16 mg o.d . ) and lisinopril ( 20 mg o.d . ) . In this article , we present data from the post-hoc subgroup of 51 type 2 diabetic subjects who completed the full 12-month study period with successful ambulatory blood pressure ( BP ) measurements  at both baseline and follow-up visits . RESULTS Baseline 24-h BP values were similar in the two groups ( 24-h systolic BP ( SBP ) 130 + /- 12 vs. 127 + /- 9 , 24-h diastolic BP ( DBP ) 77 + /- 8 vs. 74 + /- 7 , and 24-h PP 53 + /- 8 vs. 53 + /- 7 mm Hg , for the lisinopril and dual blockade groups , respectively , P > 0.2 for all ) . Compared with lisinopril monotherapy , dual blockade treatment caused a highly significant reduction in 24-h PP levels ( -5 + /- 5 mm Hg , P = 0.003 ) , albeit the difference in the BP lowering effect between the treatment groups did not differ significantly for 24-h systolic ( P = 0.21 ) or diastolic ( P = 0.49 ) BP . Dual blockade treatment significantly lowered 24-h SBP ( -5 + /- 11 mm Hg , P = 0.03 ) , but not 24-h DBP ( -2 + /- 7 mm Hg , P = 0.29 ) , whereas in the lisinopril group , the opposite effect was observed ( 24-h SBP -1 + /- 9 mm Hg , P = 0.45 , 24-h SBP -3 + /- 7 mm Hg , P = 0.03 ) . CONCLUSIONS Twelve months of dual blockade with c and esartan and lisinopril significantly reduced PP when compared with high-dose monotherapy with lisinopril . Larger studies are needed to confirm this observation , and to evaluate whether this effect translates into a greater degree of end-organ protection from dual blockade treatment than from conventional angiotensin-converting enzyme ( ACE ) inhibition BACKGROUND Aliskiren is approved for the treatment of hypertension at once-daily doses of 150 or 300 mg by the US Food and Drug Administration and the European Commission . It is generally well tolerated and provides 24-hour , dose-dependent blood pressure ( BP ) reduction ; however , the effect of the 75-mg dose has been inconsistent in previous trials . OBJECTIVES This study was design ed to assess the efficacy and tolerability of once-daily administration of aliskiren 75 mg and to evaluate the dose-response relationship across all 3 doses of aliskiren ( 75 , 150 , and 300 mg ) . METHODS In this 8-week , multicenter , r and omized , double-blind , parallel-group , placebo-controlled study , patients aged > or = 18 years with stage 1 or 2 essential hypertension entered a 3- to 4-week , single-blind , placebo run-in period . Eligible patients were r and omized ( 1:1:1:1 ) to receive oral , once-daily doses of aliskiren 75 , 150 , or 300 mg or placebo . The primary efficacy variable was the change from baseline in mean sitting diastolic BP ( msDBP ) at the week-8 end point . Tolerability was assessed by monitoring and recording all adverse events ( AEs ) . RESULTS A total of 642 patients ( mean [ SD ] age , 52.0 [ 10.73 ] years ; 60.0 % male ; 80.8 % white ; mean body weight , 89.2 [ 18.4 ] kg [ range , 50 - 160 kg ] ) were included in the study . Overall , 576 patients ( 89.7 % ) completed the double-blind treatment period . The most frequent reasons for discontinuation were unsatisfactory therapeutic effect ( 27/642 r and omized patients [ 4.2 % ] ) and AEs ( 17/642 [ 2.6 % ] ) . At end point , aliskiren 150 and 300 mg significantly reduced msDBP ( both , P < 0.001 ) and mean sitting systolic CONCLUSIONS This study found a positive linear dose-response relationship in BP reduction with aliskiren 75 , 150 , and 300 mg dosed once daily , but only aliskiren 150 and 300 mg provided statistically significant reductions from baseline compared with placebo . All 3 doses of aliskiren were generally well tolerated The primary objective of this study was to compare the antihypertensive efficacy and safety of intravenously administered nicardipine with that of intravenous nitroprusside ( SNP ) in patients with severe hypertension . The study was conducted in 121 patients with severe hypertension ( diastolic blood pressure [ BP ] > 120 mm Hg , or systolic BP > 200 mm Hg ) . Patients were r and omized to receive intravenous nicardipine or SNP .  Drugs were administered according to a predetermined dosing schedule for a 10 to 12 h period . Sixty-one patients were r and omized to intravenous nicardipine and 60 to SNP . Pretreatment BP values for the nicardipine and SNP groups were 217/128 mm Hg and 219/128 mm Hg , respectively . Therapeutic response ( diastolic BP < 100 mm Hg , or a decrease of > 15 mm Hg ; systolic BP < 180 mm Hg , or a decrease of > 20 mm Hg ) was achieved in 98 % ( 60/61 ) of patients treated with nicardipine and 93 % ( 56/60 ) of patients treated with SNP . The mean decreases in systolic and diastolic BP were 61 mm Hg and 40 mm Hg after 4 h of nicardipine , and 59 mm Hg and 38 mm Hg after 4 h of SNP . The mean increases in heart rate also were similar in both groups ( nicardipine , 12 beats/min ; SNP 10 beats/min ) . The mean numbers of dose adjustments per hour required to maintain the BP reductions were lower ( P < .01 ) in the nicardipine-treated patients ( 0.5 + /- 0.1 times per hour ) than in the SNP-treated patients ( 1.5 + /- 0.2 times per hour ) . ( ABSTRACT TRUNCATED AT 250 WORDS 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 combination of angiotensin converting enzyme ( ACE ) inhibitor and thiazide diuretic has advantages over monotherapy for the treatment of hypertension . Previous study design s have often been inadequate to demonstrate the details of interactions between these antihypertensive agents . This study used a modified 4 x 4 factorial r and omized , double-blind , placebo-controlled , parallel group design to study the efficacy of 17 different doses of fosinopril ( Fos ) , a phosphinic acid derived ACE inhibitor , and hydrochlorothiazide ( HCTZ ) in 550 patients with mild to moderate hypertension . Data from these variables were fit to quadratic response surface models ( QRSM ) using polynomial functions in the doses of the two components . Using QRSM , seated systolic ( SeSBP ) and diastolic blood pressure ( SeDBP ) responses at 8 weeks were predicted for actual doses and interpolated for intermediate doses not studied . Fos and HCTZ alone and in combination produced a dose-related reduction in SeSBP and SeDBP . Using 10 mg Fos + 12.5 mg HCTZ reduced the adjusted mean SeDBP 6.3 mm Hg and 20 mg Fos + 12.5 mg HCTZ lowered the same measure 9.1 mm Hg . Coadministration of Fos and HCTZ produced an additive antihypertensive effect . This study of combination agents for hypertension using a factorial design with QRSM accurately predicts dose responses and is a valuable clinical trial methodology BACKGROUND Blood pressure ( BP ) variability ( BPV ) is a novel risk factor for the development of atherosclerotic diseases . High BPV has recently been shown to predict all-cause and cardiovascular mortality in patients with lacunar infa rct . Whether BPV has prognostic implication s in patients with ischemic stroke subtypes , other than those due to small-vessel occlusion , remains uncertain . METHODS We prospect ively followed up the clinical outcome of 632 consecutive ischemic stroke patients without atrial fibrillation . The average BP and BPV , as determined by the coefficient of variation of the systolic and diastolic BP , were recorded during a mean 12 ± 6 outpatient clinic visits . RESULTS The average age of the population was 71 ± 11 years . After a mean of 76 ± 18 months of follow-up , 161 patients died ( 26 % ) ; 35 % ( n = 56 of 161 ) of these deaths were due to cardiovascular causes . Sixteen percent and 5 % developed recurrent stroke and acute coronary syndrome ( ACS ) , respectively . After adjusting for mean systolic BP and confounding variables , patients with high systolic BPV were at significantly greater risk of cardiovascular mortality ( hazards ratio ( HR ) = 2.36 ; 95 % confidence interval ( CI ) = 1.02 - 5.49 ; P < 0.05 ) . High systolic BPV also predicted all-cause mortality after adjusting for mean systolic BP ( HR = 1.79 ; 95 % CI = 1.16 - 2.75 ; P < 0.05 ) . There was no association between systolic BPV and nonfatal recurrent stroke or nonfatal ACS . Raised diastolic BPV did not predict recurrent nonfatal stroke , nonfatal ACS , or mortality . CONCLUSIONS Visit-to-visit systolic BPV predicts long-term all-cause and cardiovascular mortality in patients with ischemic stroke without atrial fibrillation , independent of other conventional risk factors , including average BP control
The data do not suggest that any one ACE inhibitor is better or worse at lowering BP .
ACE inhibitor doses above Max did not significantly lower BP more than Max .
There are no clinical ly meaningful BP lowering differences between different ACE inhibitors .
BACKGROUND ACE inhibitors are widely prescribed for hypertension so it is essential to determine and compare their effects on blood pressure ( BP ) , heart rate and withdrawals due to adverse effects ( WDAE ) .
OBJECTIVES To quantify the dose-related systolic and /or diastolic BP lowering efficacy of ACE inhibitors versus placebo in the treatment of primary hypertension .