Combined angiotensin-converting enzyme inhibition and receptor blockade associate with increased risk of cardiovascular death in hemodialysis patients. Combination is better than monotherapy with ACE inhibitor or angiotensin receptor antagonist at recommended doses Angiotensin converting enzyme gene polymorphism predicts blood pressure response to angiotensin II receptor type 1 antagonist treatment in hypertensive patients Inhibition of renin–angiotensin system affects prognosis of advanced pancreatic cancer receiving gemcitabine Combination of antihypertensive therapy in the elderly, multicenter investigation (CAMUI) trial. Antihypertensive medications and C-reactive protein in the multi-ethnic study of atherosclerosis. Effects of valsartan, an angiotensin II receptor blocker, on coronary atherosclerosis in patients with acute myocardial infarction who receive an angiotensin-converting enzyme inhibitor. Rationale for the use of combination angiotensin-converting enzyme inhibitor and angiotensin II receptor blocker therapy in heart failure. Effects of Angiotensin II Type 1 Receptor Blocker on Blood Pressure Variability and Cardiovascular Remodeling in Hypertensive Patients on Chronic Peritoneal Dialysis The effect of valsartan, captopril, or both on atherosclerotic events after acute myocardial infarction: an analysis of the Valsartan in Acute Myocardial Infarction Trial (VALIANT). Hemodynamic and biochemical effects of the AT1 receptor antagonist irbesartan in hypertension. Effect of angiotensin II receptor blockade on autonomic nervous system function in patients with essential hypertension. The impact of ACE inhibitors or angiotensin II type 1 receptor blockers on the development of new-onset type 2 diabetes. The Effects of Angiotensin Blocking Agents on the Progression of Liver Fibrosis in the HALT-C Trial Cohort Comparison of the effects of angiotensin receptor antagonist, angiotensin converting enzyme inhibitor, and their combination on regression of left ventricular hypertrophy of diabetes type 2 patients on recent onset hemodialysis therapy. Hemodynamic effects of the angiotensin II receptor antagonist irbesartan in patients with cirrhosis and portal hypertension. First dose response and 24-hour antihypertensive efficacy of the new once-daily angiotensin converting enzyme inhibitor, ramipril.
To compare the relative effectiveness of angiotensin-converting enzyme inhibitors ( ACEIs ) and angiotensin receptor blockers ( ARBs ) in reducing cardiovascular mortality in chronic hemodialysis patients , we conducted an observational analysis of all patients initiated on ACEI or ARB therapy undergoing chronic hemodialysis at a large dialysis provider .  Survival curves with mortality hazard ratios ( HRs ) were generated using the Kaplan-Meier method and Cox regression . Outcomes were compared using inverse probability of treatment weighting and propensity score matching . Over 6 years , 22,800 patients were newly initiated on an ACEI and 5828 on an ARB after at least 60 days of chronic hemodialysis . After adjustment for baseline cardiovascular risk factors , there was no significant difference in the risk of cardiovascular , all-cause , or cerebrovascular mortality in patients initiated on an ARB compared with an ACEI ( HR of 0.96 ) . A third of 28,628 patients , newly started on an ACEI or ARB , went on to another  antihypertensive medication  in succession . After adjustment for risk factors , 701 patients initiated on combined ACEI and ARB therapy ( HR of 1.45 ) or 6866 patients on ACEI and non-ARB antihypertensive agent ( HR of 1.27 ) were at increased risk of cardiovascular death compared with 1758 patients initiated on an ARB and non-ACEI antihypertensive therapy . Thus , an ARB , in combination with another antihypertensive medication ( but not an ACEI ) , may have a beneficial effect on cardiovascular mortality . As observational studies may be confounded by indication , even when adjusted , r and omized clinical trials are needed to confirm these findings 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 Objectives To determine whether polymorphisms in the renin – angiotensin system can predict blood pressure-lowering response to antihypertensive treatment ; more specifically , in response to treatment with irbesartan or atenolol . Design and methods Eighty-six patients with hypertension were r and omized to double-blind treatment with either the angiotensin II type 1 receptor antagonist irbesartan or the β1 adrenergic receptor blocker atenolol and followed for 3 months . We analysed angiotensinogen T174 M and M235 T , angiotensin converting enzyme ( ACE ) I/D and angiotensin II type 1 receptor A1166C polymorphisms and related them to blood pressure reduction . Results The mean reductions in blood pressure were similar for both treatments . In the irbesartan group , individuals homozygous for the ACE gene I allele showed a greater reduction in diastolic blood pressure , exceeding those with the D allele ( − 18 ± 11 SD versus − 7 ± 10 mmHg , P = 0.0096 ) . This was not the case during treatment  with atenolol  , and the interaction term between type of treatment and ACE II genotype was significant ( P = 0.0176 ) . The angiotensinogen and angiotensin II type 1 receptor polymorhisms were not related to the response to treatment . Conclusions ACE genotyping predicted the blood pressure-lowering response to antihypertensive treatment with irbesartan but not atenolol . Thus , specific genotypes might predict the response to specific antihypertensive treatment Background : The renin – angiotensin system ( RAS ) is thought to have a role in carcinogenesis , and RAS inhibition may prevent tumour growth . Methods : We retrospectively investigated the impact of angiotensin I-converting enzyme inhibitors ( ACEIs ) and angiotensin II type-1 receptor blockers ( ARBs ) in 155 patients with pancreatic cancer receiving gemcitabine monotherapy .  Patients were divided into three groups : the ACEI/ARB group ( 27 patients receiving an ACEI or ARB for hypertension ( HT ) ) , the non-ACEI/ARB with HT group ( 25 patients receiving antihypertensive drugs other than ACEIs or ARBs ) , and the non-HT group ( 103 patients receiving no antihypertensive drugs ) . Results : Patient characteristics were not different , except for age and HT medications . Progression-free survival ( PFS ) was 8.7 months in the ACEI/ARB group , 4.5 months in the non-ACEI/ARB with HT group , and 3.6 months in the non-HT group . Overall survival ( OS ) was 15.1 months in the ACEI/ARB group , 8.9 months in the non-ACEI/ARB with HT group , and 9.5 months in the non-HT group . The use of ACEIs/ARBs was a significant prognostic factor for both PFS ( P=0.032 ) and OS ( P=0.014 ) in the multivariate analysis . Conclusions : The ACEIs/ARBs in combination with gemcitabine might improve clinical outcomes in patients with advanced pancreatic cancer . Prospect i ve trials are needed to test this hypothesis Angiotensin receptor blockers ( ARBs ) with calcium channel blockers ( CCBs ) or diuretics are a widely used combination therapy for hypertensive patients . The present study aim ed to determine which combination was better for elderly hypertension patients aged ≧ 65 years . We design ed a multicentre , r and omized , open-label , parallel comparison study . Hypertensive out patients aged ≧ 65 years who did not achieve the target blood pressure ( BP < 140/90 mmHg ) with usual dosages of ARBs  were r and omly assigned to switch treatment to losartan 50 mg/hydrochlorothiazide 12.5 mg or amlodipine 5 mg in addition to ARBs . The primary endpoint was a change in the systolic blood pressure ( SBP ) and diastolic blood pressure ( DBP ) after the 3-month treatment period , while secondary endpoints were changes in the BP , albuminuria , laboratory values , and cognitive function with the mini-mental state examination ( MMSE ) at baseline and after one year . The results from the CAMUI trial should provide new evidence for selecting optimal combination therapies for elderly hypertensive patients BACKGROUND The effects of different antihypertensive medication classes on C-reactive protein ( CRP ) levels are still not well characterized , and might be of relevance to treatment choices . METHODS We studied the association between antihypertensive medication class and CRP levels among participants with treated hypertension in the Multi-Ethnic Study of Atherosclerosis . We performed a cross-sectional study of hypertensive participants free of clinical cardiovascular disease who were taking one or more of the following medication classes : beta-blockers , calcium channel blockers , diuretics , and angiotensin-converting enzyme ( ACE ) inhibitors , or angiotensin II type I receptor blockers ( ARB ) .  RESULTS Among 2340 participants taking one or more antihypertensive medications , the mean serum CRP level was lower among participants taking a beta-blocker than among those not taking a beta-blocker ( 2.13 v 2.54 mg/L , P = .002 ) . This difference persisted after multivariate adjustment ( P = .021 ) . There were no other statistically significant differences in multivariate models . Among 1314 participants receiving monotherapy , the multivariate adjusted mean CRP level among participants taking a beta-blocker was lower ( 1.97 mg/L ) than those taking a diuretic ( 2.72 mg/L , P < .001 ) . In this monotherapy group , participants taking an ACE inhibitor or ARB also had a lower adjusted mean CRP ( 2.25 mg/L ) than those taking a diuretic ( P = .046 ) . African-American race/ethnicity did not modify any of those relationships . CONCLUSIONS The beta-blocker use was associated with lower CRP levels overall and among participants on monotherapy , whereas ACE inhibitor and ARB use was associated with lower CRP levels among participants on monotherapy . These findings warrant further evaluation in r and omized trials BACKGROUND The aim of the present study was to assess the effects of angiotensin II receptor blocker ( ARB ) on coronary plaque progression in patients with acute myocardial infa rct ion ( AMI ) who received an angiotensin-converting enzyme inhibitor ( ACEI ) .  METHODS AND RESULTS After local ethics committee approval and obtaining of informed consent , 116 patients with AMI were r and omly assigned to receive a combination of valsartan and captopril or captopril alone . Non-culprit intermediate coronary atherosclerosis was assessed on intravascular ultrasound . The primary and secondary endpoints were the nominal change in percent atheroma volume ( PAV ) and percent change in lumen volume ( % ΔLV ) , respectively . The combination group had a significantly lower systolic blood pressure ( 117 vs. 125 mmHg ; P=0.02 ) and a lower plasma aldosterone level ( 56 vs. 75 pg/ml ; P=0.02 ) at follow-up . The nominal change in PAV was slightly lower in the combination group than in the ACEI group ( -1.9 vs. -0.68 % , P=0.06 ) . % ΔLV was -0.3 % in the ACEI group and was 4.3 % in the combination group ( P=0.03 ) . Logistic regression analysis showed that additional ARB therapy was independently associated with LV enlargement ( odds ratio , 2.144 ; 95 % confidence interval : 1.818 - 5.618 ; P=0.03 ) . CONCLUSIONS In this study of patients with AMI , additional ARB therapy had minimal impact on the progression of coronary atherosclerosis as compared with an ACEI alone . The combination of these 2 drugs , however , induces coronary artery enlargement BACKGROUND The present multicenter study investigated whether the combination of angiotensin-converting enzyme inhibitor ( ACEI ) and angiotensin II receptor blocker ( ARB ) is more beneficial for preventing left ventricular remodeling and suppressing neurohumoral factors than either ACEI or ARB alone . METHODS AND RESULTS One hundred and six patients with mild-to-moderate congestive heart failure treated in 26 Japanese institutes were r and omly assigned to the combination therapy or monotherapy .  Changes in physical activity ( New York Heart Association functional classes , Specific Activity Scale ( SAS ) ) , concentrations of neurohumoral factors ( plasma renin activity , angiotensin II , aldosterone , and brain natriuretic peptide ( BNP ) ) , and cardiac function for 6 months were compared between the 2 groups . It was found that the combination therapy , which was administered at doses st and ard in Japan , increased the SAS score ( 4.5 + /- 1.5 to 4.9 + /- 1.5 , p<0.05 ) and decreased the plasma BNP concentration ( 183 + /- 163 to 135 + /- 118 pg/ml , p<0.05 ) . In contrast , there were no changes in SAS score ( 4.5 + /- 1.4 to 4.6 + /- 1.4 , NS ) or BNP concentration ( 156 + /- 157 to 151 + /- 185 pg/ml , NS ) in the patients receiving monotherapy . CONCLUSIONS The results of the study demonstrate that the combination therapy , even at the st and ard doses for Japan , improves physical activity and plasma BNP concentration more than the monotherapy . A larger study is required to assess the effects of the combination therapy on major clinical outcomes Aims : In this study , we examined whether addition of an angiotensin II type 1 receptor blocker ( ARB ) , c and esartan or valsartan , to conventional antihypertensive treatment could improve blood pressure ( BP ) variability in hypertensive patients on peritoneal dialysis . Methods : 45 hypertensive patients on chronic peritoneal dialysis therapy were r and omly assigned to the ARB treatment groups either by c and esartan ( n = 15 ) or valsartan ( n = 15 ) , or the control group ( n = 15 ) . At baseline and 6 months after the treatment , 24-hour ambulatory BP monitoring , echocardiography  , and measurement of brachial-ankle pulse wave velocity ( baPWV ) were performed . Results : After the 6 months of treatment , 24-hour ambulatory BP values were similarly decreased in both the control group and ARB groups . However , short-term BP variability assessed on the basis of the st and ard deviation of 24-hour ambulatory BP was significantly decreased in the ARB groups , but remained unchanged in the control group . Furthermore , parameters of cardiovascular remodeling assessed by natriuretic peptides , echocardiography , and baPWV were significantly improved in the ARB groups but not in the control group . Conclusion : ARB treatment and control antihypertensive treatment similarly controlled 24-hour ambulatory BP values in hypertensive patients on peritoneal dialysis . However , ARB treatment is beneficial for the suppression of pathological cardiovascular remodeling with a decrease in BP variability OBJECTIVES We attempted to compare the effect of an angiotensin-converting enzyme ( ACE ) inhibitor and angiotensin receptor blocker ( ARB ) on  atherosclerotic events . BACKGROUND Angiotensin-converting enzyme inhibitors and ARBs interrupt the renin-angiotensin system by distinct mechanisms . It is not clear whether ARBs reduce atherosclerotic events such as myocardial infa rct ion ( MI ) like ACE inhibitors . This evidence gap may reflect the nature of the studies conducted , to date . Placebo-controlled studies enrolled cohorts at low risk of atherosclerotic events ( e.g. , patients with chronic heart failure , most treated with an ACE inhibitor ) . One of the main active controlled trials was confounded by a blood pressure difference between treatments . METHODS We compared the effects of captopril , valsartan , and their combination on atherosclerotic events in 14,703 patients r and omized in the Valsartan in Acute Myocardial Infa rct ion Trial ( VALIANT ) . RESULTS The number of individuals adjudicated as having a fatal or non-fatal MI in the captopril group was 559 ( total investigator reported events 798 ) , 587 ( 796 ) in the valsartan group , and 554 ( 756 ) in the combination group ; valsartan versus captopril , p = 0.651 ( 0.965 ) ; combination versus captopril , p = 0.187 ( 0.350 ) . Overall , all atherosclerotic events examined occurred at a similar frequency in the captopril and valsartan groups . CONCLUSIONS Angiotensin receptor blockers appear to be as effective as ACE inhibitors in reducing atherosclerotic events , even when used in addition to other secondary preventive treatments . These data , although not conclusive , also support the hypothesis that adding an ARB to an ACE inhibitor may have a small additional anti-infa rct ion effect , a possibility that needs to be prospect ively tested We studied the hemodynamic , neurohumoral , and biochemical effects of the novel angiotensin type 1 ( AT1 ) receptor antagonist irbesartan in 86 untreated patients with essential hypertension on a normal sodium diet . According to a double-blind parallel group trial , patients were r and omized to a once-daily oral dose of the AT1 receptor antagonist ( 1 , 25 , or 100 mg ) or placebo after a placebo run-in period of 3 weeks . R and omization medication was given for 1 week . Compared with placebo , 24-hour ambulatory blood pressure did not change with the 1-mg dose , and it fell ( mean and 95 % confidence interval ) by 7.0 (4.2 - 9.8)/6.1 ( 3.9 - 8.1 ) mm Hg with the 25-mg dose and by 12.1 (8.1 - 16.2)/7.2 ( 4.9 - 9.4 ) mm Hg with the 100-mg dose . Heart rate did not change during either dose . With the 25-mg dose , the antihypertensive effect was attenuated during the second half of the recording , and with the 100-mg dose , it was maintained for 24 hours . Baseline values of renin and the antihypertensive response to the 25- and 100-mg doses were well correlated ( r = .68 , P < .01 ) . Renin did not change with the 1-mg dose , but it rose threefold to fourfold with the 25-mg dose and fourfold to fivefold with the 100-mg dose 4 to 6 hours after administration . With the 100-mg dose , renin was still elevated twofold 24 hours after dosing . The changes in renin induced by the AT1 receptor antagonist were associated with parallel increments in angiotensin I and angiotensin II . Aldosterone , despite AT1 receptor blockade , did not fall . ( ABSTRACT TRUNCATED AT 250 WORDS It has long been proposed that the renin-angiotensin system exerts a stimulatory influence on the sympathetic nervous system , including augmentation of central sympathetic outflow and presynaptic facilitation of norepinephrine release from sympathetic nerves . We tested this proposition in 19 patients with essential hypertension , evaluating whether the angiotensin receptor blockers ( ARBs ) eprosartan and losartan had identifiable antiadrenergic properties . This was done in a prospect i ve , r and omized , three-way placebo-controlled study of crossover design . Patients were r and omized to 600 mg of eprosartan daily , 50 mg of losartan daily , or placebo . The treatment period was 4 wk , with 2-wk washout periods . Multiunit firing rates in efferent sympathetic nerves distributed to skeletal muscle vasculature ( muscle sympathetic nerve activity , MSNA ) were measured with microneurography , testing whether ARBs inhibit central sympathetic outflow . In parallel , isotope dilution methodology was used to measure whole body norepinephrine spillover to plasma . Mean blood pressure on placebo was 151/98 mmHg , with both ARBs causing reductions of approximately 11 mmHg systolic and 6 mmHg diastolic pressure , placebo corrected . Both MSNA [ 35 + /- 12 bursts/min ( mean + /- SD ) on placebo ] and whole body norepinephrine spillover [ 366 + /- 247 ng/min ] were unchanged by ARB administration , indicating that the ARBs did not material ly inhibit central sympathetic outflow or act presynaptically to reduce norepinephrine release at existing rates of nerve firing . These findings contrast with the easily demonstrable reduction in sympathetic nervous activity produced by antihypertensive drugs of the imidazoline-binding class , which are known to act within the brain to inhibit sympathetic nervous outflow . We conclude that sympathetic nervous inhibition is not a major component of the blood pressure-lowering action of ARBs in essential hypertension OBJECTIVE Angiotensin II has been shown to increase hepatic glucose production and decrease insulin sensitivity . Patients who utilize either an ACE inhibitor ( ACEI ) or angiotensin receptor blocker ( ARB )  may experience a decreased incidence of new-onset type 2 diabetes . RESEARCH DESIGN AND METHODS Three review ers conducted a systematic literature search of Medline , EMBASE , CINAHL , and the Cochrane Library ( 1966 to present ) to extract a consensus of trial data involving an ACEI or ARB with an end point of new-onset type 2 diabetes . Studies were included if they were r and omized controlled trials verses placebo/routine therapy . A r and om-effects model was utilized . Subgroup and sensitivity analyses were conducted . RESULTS Eleven trials were identified , including 66,608 patients . An ACEI or ARB prevented new-onset type 2 diabetes ( odds ratio 0.78 [ 95 % CI 0.73 - 0.83 ] ) . The influence of either an ACEI ( six trials ) or an ARB ( five trials ) alone on new-onset type 2 diabetes was similar ( 0.79 [ 0.71 - 0.89 ] and 0.76 [ 0.70 - 0.82 ] , respectively ) . Regardless of indication for use , hypertension ( seven trials ) , coronary artery disease ( two trials ) , or heart failure ( two trials ) , reductions in new-onset type 2 diabetes were maintained ( 0.79 [ 0.72 - 0.85 ] , 0.76 [ 0.60 - 0.95 ] , and 0.70 [ 0.50 - 0.96 ] , respectively ) . No statistical heterogeneity was observed for any evaluation ( P > 0.1 for all comparisons ) . ACEIs and ARBs did not reduce the odds of mortality , cardiovascular , or cerebrovascular events versus control therapy among all of these studies combined or the hypertension trials . ACEIs and ARBs did reduce the odds of these outcomes among the coronary artery disease studies versus control therapy . CONCLUSIONS ACEIs or ARBs may decrease patients ' odds of developing new-onset type 2 diabetes but does not reduce the odds of mortality , cardiovascular , or cerebrovascular outcomes over the study follow-up periods among patients with hypertension Background Therapies that can slow the progression of liver fibrosis in chronic liver disease are needed . Evidence suggests that the renin-angiotensin system ( RAS ) contributes to inflammation and fibrosis in chronic liver disease . Both animal and limited human studies have shown that RAS inhibition with angiotensin-converting enzyme inhibitors ( ACEi ) and angiotensin receptor-1 [ AT-1 ] blockers ( ARBs ) has antifibrogenic properties . Aims In this study , we evaluated the effects of continuous ACEi/ARB use for 3.5 years on histological liver fibrosis progression in the HALT-C Trial cohort . Methods In the HALT-C Trial , subjects with chronic hepatitis C and advanced hepatic fibrosis ( Ishak stage ≥3 ) underwent serial liver biopsies at baseline , 1.5 years , and 3.5 years after r and omization . The primary outcome was a ≥2-point increase in Ishak fibrosis score in at least one of the two serial biopsies . Sixty-six subjects were continuously taking ACEi/ARBs over the observation period , 126 were taking other antihypertensive medications , and 343 subjects took no antihypertensive medications . Results The three groups were similar in baseline fibrosis scores , and the two groups being treated with antihypertensives were taking a similar number of antihypertensive medications . Fibrosis progression occurred in 33.3 % of the ACEi/ARB group , 32.5 % of the other antihypertensive medications group , and in 25.7 % of subjects taking no antihypertensive medications . No significant associations between ≥2-point increases in fibrosis scores and continuous ACEi/ARB use were apparent at either 1.5 or 3.5 years in diabetes-adjusted and unadjusted odds ratios . Conclusions ACEi/ARB therapy did not retard the progression of hepatic fibrosis Left ventricular hypertrophy ( LVH ) is frequently found at the initiation of dialysis therapy of diabetic and hypertensive patients , and is highly predictive of future cardiac morbidity and mortality . In patients with hypertension and LVH , both an angiotensin converting enzyme ( ACE ) inhibitor and an angiotensin type 1 receptor ( AT1 ) antagonist regress LVH . However , it remains controversial whether dual blockade of the renin-angiotensin system will regress LVH in these patients using a combination of ACE inhibitor and AT1 antagonist . Thirty-three type II diabetic patients with end-stage renal disease who had just entered into hemodialysis therapy and were diagnosed as having LVH evaluated by echocardiography were selected from three dialysis units staffed by the faculty of Saitama Medical School , Saitama , Japan between 1999 and 2001 . The study was carried out for 1 year . All patients were assigned r and omly to three groups with equal number : group I , an ACE inhibitor , enalapril 10 mg daily ; group II , an AT1 antagonist , losartan 100 mg daily ; group III , combination of enalapril 10 mg and losartan 100 mg daily . All antihypertensive drugs were given 30 min after the cessation of dialysis therapy .  LVH was evaluated by echocardiography before the start of administration of drugs , at 6 months and 12 months after the start of drug therapy . Systolic blood pressure levels less than 140 mmHg were the target for the three groups . Using repeated measures analysis of variance , applied to those with four echocardiograms , there were progressive decreases over time in left ventricular mass index , posterior wall thickness and interventricular septum thickness . There were no significant differences in regression of LVH as well as blood pressure control between enalapril and losartan groups ; however , dual blockade induced an additional 28 % reduction in left ventricular mass index compared with any type of monotherapy . Both ACE inhibitors and AT1 antagonists benefit the regression of LVH in diabetic patients who start dialysis therapy . Moreover , combination therapy with ACE inhibitors and AT1 antagonists would provide more beneficial effects on LVH in these patients than monotherapy BACKGROUND & AIMS Angiotensin II receptor antagonists have been proposed as new drugs for portal hypertension . This r and omized , placebo-controlled , double-blind study aim ed to assess the effect of the angiotensin II receptor antagonist irbesartan on portal and systemic hemodynamics and renal function in patients with cirrhosis . METHODS Thirty-six patients with cirrhosis and portal hypertension received 150 mg/d irbesartan or placebo for 1 week . Systemic hemodynamics , kidney and liver function parameters were recorded regularly ; hepatic venous pressure gradient and plasma renin were assessed on days 0 and 7 . RESULTS Irbesartan reduced the hepatic venous pressure gradient by 12.2 % + /- 6.6 % ( P < 0.05 ) and mean arterial pressure by 5.3 % + /- 4.0 % in 13 of 18 verum patients . In 4 ( 22 % ) verum patients , arterial hypotension , accompanied by significant renal impairment , required withdrawal of irbesartan . In these patients , baseline plasma renin ( P < 0.002 ) and cystatin C ( P < 0.001 ) levels were higher , and creatinine clearance ( P < 0.02 ) , serum sodium ( P < 0.01 ) , and albumin ( P < 0.05 ) were lower than in patients who tolerated irbesartan . Four of five patients with baseline renin > 900 microU/mL developed treatment-limiting hypotension . CONCLUSIONS The angiotensin II receptor antagonist irbesartan is not advisable in patients with advanced cirrhosis and high plasma renin because it may induce arterial hypotension and only moderately reduces portal pressure 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
RESULTS The global antihypertensive activity of ARB differs from that observed with amlodipine in the sense that the magnitude of the reduction in the BP values does not essentially depend on the initial BP values nor on the dose used .
When only ARB were considered , the drug used was a determinant for systolic BP reduction , whereas for diastolic BP the influence was on the BP reduction and the duration of the antihypertensive activity .
The dose used had a particular influence on the duration of the antihypertensive activity for both systolic and diastolic BP .
CONCLUSION Among the ARB , the influence is on duration more than on the magnitude of BP reduction .
Dose , therefore , is an important factor in the duration of antihypertensive activity
OBJECTIVE To perform a systematic review of the antihypertensive activity of the angiotensin II AT1 receptor antagonists ( ARB ) .