Effects of Celecoxib on Ambulatory Blood Pressure in Hypertensive Patients on ACE Inhibitors Effect of aspirin on blood pressure in hypertensive patients taking enalapril or losartan. Efficacy of Eplerenone Added to Renin-Angiotensin Blockade in Hypertensive Patients Antihypertensive efficacy of manidipine and enalapril in hypertensive diabetic patients. A 16-week, randomized, double-blind, placebo-controlled, crossover trial to quantify the combined effect of an angiotensin-converting enzyme inhibitor and a beta-blocker on blood pressure reduction. Combination of an ACE inhibitor and indapamide improves blood pressure control, but attenuates the beneficial effects of ACE inhibition on plasma adiponectin in patients with essential hypertension. Aliskiren, an oral renin inhibitor, provides dose-dependent efficacy and sustained 24-hour blood pressure control in patients with hypertension. Combination of hydrochlorothiazide or benazepril with valsartan in hypertensive patients unresponsive to valsartan alone Effect of candesartan and lisinopril alone and in combination on blood pressure and microalbuminuria Tricenter assessment of the efficacy of the ACE inhibitor, moexipril, by ambulatory blood pressure monitoring. Additive hypotensive effect of angiotensin-converting enzyme inhibition and angiotensin-receptor antagonism in essential hypertension. Ambulatory blood pressure monitoring in the evaluation of antihypertensive treatment: additional information from a large data base. Additive effects of verapamil and enalapril in the treatment of mild to moderate hypertension. Effect of indomethacin on blood pressure in elderly people with essential hypertension well controlled on amlodipine or enalapril. Progress Report on the Hypertension Objective Treatment Based on Measurement by Electrical Devices of Blood Pressure (HOMED-BP) Study: Status at February 2004 ACE inhibitors, beta-blockers, calcium blockers, and diuretics for the control of systolic hypertension. Effect of ramipril on ambulatory blood pressure and albuminuria in renal hypertension Effect of angiotensin receptor blockade on central haemodynamics in essential hypertension: results of a randomised trial Antihypertensive efficacy and safety of olmesartan medoxomil and ramipril in elderly patients with mild to moderate essential hypertension: the ESPORT study The influence of long-term ACE inhibitor treatment on circulatory responses to stress in human hypertension. A prospective evaluation of persistence on antihypertensive treatment with different antihypertensive drugs in clinical practice Twenty-four hour blood pressure effect of once-daily lisinopril, enalapril, and placebo in patients with mild to moderate hypertension. Sibutramine is safe and effective for weight loss in obese patients whose hypertension is well controlled with angiotensin-converting enzyme inhibitors
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
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 .