Combined angiotensin-converting enzyme inhibition and receptor blockade associate with increased risk of cardiovascular death in hemodialysis patients. The impact of ACE inhibitors or angiotensin II type 1 receptor blockers on the development of new-onset type 2 diabetes. Angiotensin-converting-enzyme inhibition in stable coronary artery disease. Reduction of morbidity and mortality by statins, angiotensin-converting enzyme inhibitors, and angiotensin receptor blockers in patients with chronic obstructive pulmonary disease. Population-based study of statins, angiotensin II receptor blockers, and angiotensin-converting enzyme inhibitors on pneumonia-related outcomes. A comparison of outcomes with angiotensin-converting--enzyme inhibitors and diuretics for hypertension in the elderly. Rationale for the use of combination angiotensin-converting enzyme inhibitor and angiotensin II receptor blocker therapy in heart failure. Inhibition of renin–angiotensin system affects prognosis of advanced pancreatic cancer receiving gemcitabine Mortality Rates in Elderly Patients Who Take Different Angiotensin-Converting Enzyme Inhibitors after Acute Myocardial Infarction: A Class Effect? Effect of angiotensin receptor blockade on central haemodynamics in essential hypertension: results of a randomised trial Renoprotective Effect of the Addition of Losartan to Ongoing Treatment with an Angiotensin Converting Enzyme Inhibitor in Type-2 Diabetic Patients with Nephropathy Combination is better than monotherapy with ACE inhibitor or angiotensin receptor antagonist at recommended doses Current Guidelines for Using Angiotensin-Converting Enzyme Inhibitors and Angiotensin IIReceptor Antagonists in Chronic Kidney Disease: Is the Evidence Base Relevant to Older Adults? Comparison of angiotensin-converting enzyme inhibitor alone and in combination with irbesartan for the treatment of heart failure. Cardiovascular events in elderly patients with isolated systolic hypertension. A subgroup analysis of treatment strategies in STOP‐Hypertension‐2 Effects of valsartan, an angiotensin II receptor blocker, on coronary atherosclerosis in patients with acute myocardial infarction who receive an angiotensin-converting enzyme inhibitor. A five-year comparison of the renal protective effects of angiotensin-converting enzyme inhibitors and angiotensin receptor blockers in patients with non-diabetic nephropathy.
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 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 Angiotensin-converting-enzyme ( ACE ) inhibitors are effective in reducing the risk of heart failure , myocardial infa rct ion , and death from cardiovascular causes in patients with left ventricular systolic dysfunction or heart failure . ACE inhibitors have also been shown to reduce atherosclerotic complications in patients who have vascular disease without heart failure . METHODS In the Prevention of Events with Angiotensin Converting Enzyme Inhibition ( PEACE ) Trial , we tested the hypothesis that patients with stable coronary artery disease and normal or slightly reduced left ventricular function derive therapeutic benefit from the addition of ACE inhibitors to modern conventional therapy . The trial was a double-blind , placebo-controlled study in which 8290 patients were r and omly assigned to receive either  tr and olapril  at a target dose of  4 mg  per  day ( 4158 patients ) or matching placebo ( 4132 patients ) . RESULTS The mean ( + /-SD ) age of the patients was 64+/-8 years , the mean blood pressure 133+/-17/78+/-10 mm Hg , and the mean left ventricular ejection fraction 58+/-9 percent . The patients received intensive treatment , with 72 percent having previously undergone coronary revascularization and 70 percent receiving lipid-lowering drugs . The incidence of the primary end point -- death from cardiovascular causes , myocardial infa rct ion , or coronary revascularization -- was 21.9 percent in the tr and olapril group , as compared with 22.5 percent in the placebo group ( hazard ratio in the tr and olapril group , 0.96 ; 95 percent confidence interval , 0.88 to 1.06 ; P=0.43 ) over a median follow-up period of 4.8 years . CONCLUSIONS In patients with stable coronary heart disease and preserved left ventricular function who are receiving " current st and ard " therapy and in whom the rate of cardiovascular events is lower than in previous trials of ACE inhibitors in patients with vascular disease , there is no evidence that the addition of an ACE inhibitor provides further benefit in terms of death from cardiovascular causes , myocardial infa rct ion , or coronary revascularization OBJECTIVES The purpose of this study was to determine if statins ( hydroxymethylglutaryl CoA reductase inhibitors [ HMG-CoA ] ) , angiotensin-converting enzyme ( ACE ) inhibitors , and angiotensin receptor blockers ( ARBs ) reduce cardiovascular ( CV ) events and pulmonary morbidity in chronic obstructive pulmonary disease ( COPD ) patients . BACKGROUND Few current COPD therapies alter prognosis . Although statins , ACE inhibitors , and ARBs improve outcomes in CV population s , their benefits in COPD patients both with and without concomitant heart disease has not previously been studied . METHODS A time-matched nested case-control study of two population -based retrospective cohorts was undertaken : 1 ) COPD patients having undergone coronary revascularization ( high CV risk cohort ) ; and 2 ) COPD patients without previous myocardial infa rct ion ( MI ) and newly treated with nonsteroidal anti-inflammatory drugs ( low CV risk cohort ) . Prespecified outcomes were COPD hospitalization , MI , and total mortality . RESULTS These drugs reduced both CV and pulmonary outcomes , with the largest benefits occurring with the combination of statins and either ACE inhibitors or ARBs . This combination was associated with a reduction in COPD hospitalization ( risk ratio [ RR ] 0.66 , 95 % confidence interval [ CI ] 0.51 to 0.85 ) and total mortality ( RR 0.42 , 95 % CI 0.33 to 0.52 ) not only in the high CV risk cohort but also in the low CV risk cohort ( RR 0.77 , 95 % CI 0.67 to 0.87 , and RR 0.36 , 95 % CI 0.28 to 0.45 , respectively ) . The combination also reduced MI in the high CV risk cohort ( RR 0.39 , 95 % CI 0.31 to 0.49 ) . Benefits were similar when steroid users were included . CONCLUSIONS These agents may have dual cardiopulmonary protective properties , thereby substantially altering prognosis of patients with COPD . These findings need confirmation in r and omized clinical trials BACKGROUND Studies suggest that statins and angiotensin-converting enzyme ( ACE ) inhibitors might be beneficial for the treatment of infections . Our purpose was to examine the association of statin , ACE inhibitor , and angiotensin II receptor blocker ( ARB ) use with  pneumonia-related outcomes . METHODS We conducted a retrospective cohort study using Department of Veterans Affairs data of patients aged ≥ 65 years hospitalized with pneumonia . We performed propensity-score matching for 3 medication classes simultaneously . RESULTS Of 50119 potentially eligible patients , we matched 11498 cases with 11498 controls . Mortality at 30 days was 13 % ; 34 % used statins , 30 % ACE inhibitors , and 4 % ARBs . In adjusted models , prior statin use was associated with decreased mortality ( odds ratio [ OR ] , 0.74 ; 95 % confidence interval [ CI ] , .68-.82 ) and mechanical ventilation ( OR , 0.81 ; 95 % CI , .70-.94 ) , and inpatient use with decreased mortality ( OR , 0.68 ; 95 % CI , .59-.78 ) and mechanical ventilation ( OR , 0.68 ; 95 % CI , .60-.90 ) . Prior ( OR , 0.88 ; 95 % CI , .80-.97 ) and inpatient ( OR , 0.58 ; 95 % CI , .48-.69 ) ACE inhibitor use was associated with decreased mortality . Prior ( OR , 0.73 ; 95 % CI , .58-.92 ) and inpatient ARB use ( OR , 0.47 ; 95 % CI , .30-.72 ) was only associated with decreased mortality . Use of all 3 medications was associated with reduced length of stay . CONCLUSIONS Statins , and to a lesser extent ACE inhibitors and ARBs , are associated with improved pneumonia-related outcomes . Prospect i ve cohort and r and omized controlled trials are needed to examine potential mechanisms of action and whether acute initiation at the time of presentation with these infections is beneficial BACKGROUND Treatment of hypertension with diuretics , beta-blockers , or both leads to improved outcomes . It has been postulated that agents that inhibit the renin-angiotensin system confer benefit beyond the reduction of blood pressure alone . We compared the outcomes in older subjects with hypertension who were treated with angiotensin-converting-enzyme ( ACE ) inhibitors with the outcomes in those treated with diuretic agents . METHODS We conducted a prospect i ve , r and omized , open-label study with blinded assessment of end points in 6083 subjects with hypertension who were 65 to 84 years of age and received health care at 1594 family practice s. Subjects were followed for a median of 4.1 years , and the total numbers of cardiovascular events in the two treatment groups were compared with the use of multivariate proportional-hazards models . RESULTS At base line , the treatment groups were well matched in terms of age , sex , and blood pressure . By the end of the study , blood pressure had decreased to a similar extent in both groups ( a decrease of 26/12 mm Hg ) . There were 695 cardiovascular events or deaths from any cause in the ACE-inhibitor group ( 56.1 per 1000 patient-years ) and 736 cardiovascular events or deaths from any cause in the diuretic group ( 59.8 per 1000 patient-years ; the hazard ratio for a cardiovascular event or death with ACE-inhibitor treatment was 0.89 [ 95 percent confidence interval , 0.79 to 1.00 ] ; P=0.05 ) . Among male subjects , the hazard ratio was 0.83 ( 95 percent confidence interval , 0.71 to 0.97 ; P=0.02 ) ; among female subjects , the hazard ratio was 1.00 ( 95 percent confidence interval , 0.83 to 1.21 ; P=0.98 ) ; the P value for the interaction between sex and treatment-group assignment was 0.15 . The rates of nonfatal cardiovascular events and myocardial infa rct ions decreased with ACE-inhibitor treatment , whereas a similar number of strokes occurred in each group ( although there were more fatal strokes in the ACE-inhibitor group ) . CONCLUSIONS Initiation of antihypertensive treatment involving ACE inhibitors in older subjects , particularly men , appears to lead to better outcomes than treatment with diuretic agents , despite similar reductions of blood pressure 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 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 Context Do all angiotensin-converting enzyme ( ACE ) inhibitors similarly improve survival after myocardial infa rct ion ? Contribution This retrospective study linked hospital and prescription data from 18 453 patients 65 years of age and older who were admitted to 109 Canadian hospitals for myocardial infa rct ion in the late 1990s . Patients who filled prescriptions for ramipril had lower mortality rates within the first year of hospital discharge than did those who filled prescriptions for several other ACE inhibitors , including captopril , enalapril , fosinopril , and quinapril . Caution s Although analyses controlled for multiple potential confounders , the authors could not adjust for unmeasured factors that might make the risk for death seem related to a particular ACE inhibitor . The Editors Many r and omized , controlled trials have shown that the use of angiotensin-converting enzyme ( ACE ) inhibitors after the occurrence of an acute myocardial infa rct ion improves survival and reduces the risk for a subsequent acute myocardial infa rct ion ( 1 - 7 ) . Although not all ACE inhibitors have been studied , they are invariably used in practice because physicians probably assume a class effect . A class effect implies that all drugs in a class exert the same effects , whether positive or negative , on their target population ( 8) . Angiotensin-converting enzyme inhibitors have been shown to be effective in treating essential hypertension ( 9 ) , renal disease ( 10 ) , and left ventricular dysfunction ( 11 ) , as well as in improving survival after acute myocardial infa rct ion ( 12 ) . Although beneficial effects might occur with all drugs in this class , the extent of benefit may vary with each drug ( 13 ) . Moreover , the varying pharmacologic and structural characteristics of ACE inhibitors influence the potency and bioavailability of each drug and could result in varying effectiveness . Several other classes of medications , including cardiac medications , have shown heterogeneous effects ( 14 ) . The lipid-lowering agent cerivastatin has been removed from the market because an unusually high proportion of patients experienced rhabdomyolysis ( 15 ) . Individual calcium-channel blockers have also differed in terms of their beneficial and side effects ( 16 , 17 ) . In fact , research ers have suggested that within the classes of both nitrates ( 18 ) and calcium-channel blockers ( 19 ) , short-acting and long-acting drugs exhibit different properties . The tendency for physicians to assume a class effect can be seen by the increase in prescriptions for ramipril in patients who have had acute myocardial infa rct ion ( 20 ) since the publication of the Heart Outcomes Prevention Evaluation ( HOPE ) ( 21 ) . However , the protocol for this trial did not specifically target patients in the period immediately after acute myocardial infa rct ion . In practice , physicians seem to assume that ramipril is indicated for secondary prevention after acute myocardial infa rct ion , even in patients without congestive heart failure ( CHF ) ( 22 - 24 ) . Our study examined the class effect of ACE inhibitors on 1-year mortality when the ACE inhibitors were prescribed to elderly patients immediately after acute myocardial infa rct ion . Methods Study Group and Data Sources We used the administrative data base that stores the information on hospital discharge summaries for the province of Quebec ( Maintenance et Exploitation des Donnes pour l'tude de la Clientle Hospitalire [ Med-Echo ] ) to create a cohort of patients 65 years of age or older who were hospitalized for acute myocardial infa rct ion and were alive at discharge . Patients were identified on the basis of a discharge diagnosis of acute myocardial infa rct ion ( International Classification of Diseases , Ninth Revision , code 410 ) between 1 April 1996 and 31 March 2000 . Using encrypted Medicare numbers , we then linked this cohort with the physician and drug cl aims data base for the province of Quebec ( the Rgie de l'Assurance Maladie du Qubec [ RAMQ ] ) . This latter data base contains information on all outpatient prescriptions for patients 65 years of age or older as well as all inpatient and outpatient diagnostic and therapeutic procedures in Quebec . This data base provides survival status for more than 99 % of patients ( 25 ) . We identified a total of 18 453 patients who had had an acute myocardial infa rct ion ; 41 % were prescribed ACE inhibitors at discharge after the acute myocardial infa rct ion ( Figure 1 ) . Figure 1 . Flow diagram . Demographic , Clinical , and Hospital Characteristics As many as 15 secondary diagnoses can be included in the hospital discharge summary data base ; these secondary diagnoses were used to obtain data about patient comorbid conditions at discharge . We also identified the following in-hospital invasive procedures : cardiac catheterization , percutaneous coronary intervention , and coronary artery bypass graft surgery . In addition , cardiac medications that may influence survival after acute myocardial infa rct ion were identified . Finally , we obtained information on the specialty of the treating physician ( 3 categories [ cardiologist , internist , or general practitioner and others ] ) , as well as on the following characteristics of the hospital in which the acute myocardial infa rct ion was treated : availability of cardiac catheterization , annual acute myocardial infa rct ion volume ( 100 or < 100 acute myocardial infa rct ions per year ) , and urban or rural location . Prescription Groups We identified patients who filled at least 1 prescription for an ACE inhibitor within 30 days of discharge . This time frame was used to include patients who may not have filled their prescriptions immediately , despite receiving them at discharge . Almost all patients who have an acute myocardial infa rct ion fill their first prescription within 30 days of discharge ( 26 ) . The patients were categorized into groups according to the ACE inhibitor on their first prescription filled after discharge . Patients who were switched to another ACE inhibitor during the first year after discharge were excluded because switching often indicates worse prognosis ( 27 ) . To determine the extent to which patients followed their treatment regimens for each ACE inhibitor , we calculated several measures of treatment adherence . Among patients with discharge prescriptions , we calculated the proportion of patients who also filled at least 1 prescription during the period 275 to 365 days ( that is , 9 to 12 months ) after discharge . In addition , we calculated persistence of filled prescriptions as the proportion of time for which a patient was covered by prescriptions during the first year after discharge or the proportion of time until death if the patient died earlier . These measures were calculated on the basis of a variable indicating the duration of each filled prescription available in the drug cl aims data base . We also calculated the proportion of patients for whom persistence was 80 % or higher . Time-Dependent Covariates We created 2 time-dependent variables . One indicated periods of exposure and nonexposure for each patient , according to information on date s when subsequent prescriptions were filled and on duration of these prescriptions . The other indicated dosage category ( no drug , below target , or at- or above-target ) . The target dosage of each drug was identified from r and omized , controlled trials ( 26 , 28 ) . Administrative data bases do not have a code for missing variables . We assumed that patients with a missing variable for a secondary diagnosis did not have that diagnosis . Validity studies have been performed specifically for the Quebec administrative data base and for other similar Canadian data bases in general ( 29 ) . Overall , few data seem to be missing when the data bases are vali date d against chart review , especially for variables that are linked to reimbursement , such as prescriptions and physicians services . The variables for prescriptions include type of drug , dosage category , frequency , and duration . For prescriptions , the variable for dosage was missing for 69 patients ( 0.9 % ) , and we have attributed the most frequently used dosage of the particular ACE inhibitor to the missing value . Statistical Analysis We compared demographic , clinical , physician , and hospital characteristics of patients according to the type of ACE inhibitor prescribed at discharge . Unadjusted mortality throughout 1 year of follow-up for users of each ACE inhibitor was summarized by using KaplanMeier curves and compared by using the log-rank test . To account for differences in follow-up and to control for differences among patients ' characteristics , a multivariable Cox proportional hazards model ( 27 ) was used . In all Cox models , the associations between particular ACE inhibitors and mortality within the first year were adjusted for the following fixed variables : age , sex , CHF , diabetes , cardiac dysrhythmia , cerebrovascular disease , acute renal failure , malignant conditions , shock , in-hospital procedures ( cardiac catheterization , percutaneous coronary intervention , coronary artery bypass graft surgery ) , discharge medications ( -blockers , lipid-lowering agents , nitrates , aspirin , calcium-channel blockers , diuretics , warfarin ) , the year of acute myocardial infa rct ion to account for temporal trends , physician specialty , and 2 hospital characteristics ( availability of cardiac catheterization and acute myocardial infa rct ion volume ) . Forced-entry regression was used to include these variables in all multivariable models in order to adjust the between-drug comparisons for potential confounders . Because ramipril has increasingly been used in the period immediately after acute myocardial infa rct ion ( as a result of the HOPE study ) it was a priori selected as a reference category , and adjusted hazard ratios were estimated for the other ACE inhibitors in comparison with ramipril . The date of 31 March 2001 was used as a censoring point for patients still alive , which enabled us to have 1 year of follow-up information for all patients . As in our 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 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 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 Key Summary Points Almost one half of adults in the general population who meet criteria for chronic kidney disease are older than 70 years . Persons older than 70 years are underrepresented in most trials underpinning major U.S. practice guidelines for the use of angiotensin-converting enzyme ( ACE ) inhibitors and angiotensin IIreceptor blockers ( ARBs ) in chronic kidney disease . More than 85 % of persons older than 70 years who meet criteria for chronic kidney disease do not have proteinuria . The relevance of guideline trials to this group may be limited because most favored inclusion of participants with proteinuria . Differences between guidelines in criteria for the use of ACE inhibitors and ARBs in chronic kidney disease lead to considerable variation across guidelines in the proportion of older adults targeted . Practice guidelines specifically recommend the use of ACE inhibitors and ARBs in patients with chronic kidney disease because these agents are renoprotective . However , slowing progression of kidney disease may not be the most patient-centric goal of therapy in many older adults with this condition . Angiotensin-converting enzyme ( ACE ) inhibitors and angiotensin IIreceptor blockers ( ARBs ) are widely recommended in clinical practice guidelines for patients with chronic kidney disease . Such recommendations are based on the results of r and omized , controlled trials ( RCTs ) demonstrating that these agents slow progression of kidney disease . The unique renoprotective properties of ACE inhibitors and ARBs are generally attributed to their ability to reduce proteinuria ( 1 , 2 ) . Proteinuria is a major risk factor for end-stage renal disease ( 3 , 4 ) and may play a direct pathogenic role in progression of chronic kidney disease ( 2 ) . In RCTs , both ACE inhibitors and ARBs are more likely to slow progression of kidney disease in participants with greater degrees of proteinuria ( 57 ) . In patients without diabetes excreting less than 500 mg/d of protein , ACE inhibitors may be no more renoprotective than other antihypertensive agents ( 7 ) . Use of these agents in patients with chronic kidney disease m and ates close monitoring for acute renal failure and hyperkalemia , may require dietary modification or long-term administration of an ion-exchange resin , and may limit the use of other medications that also increase serum potassium level ( 8) . More than one third of adults in the general population age 70 years or older have chronic kidney disease ( 9 ) . Whether evidence supporting current guidelines for the use of ACE inhibitors and ARBs in chronic kidney disease can be extrapolated to this large group is unknown . To address this question , we first examined the representation of older adults in RCTs used to formulate contemporary guidelines from the Kidney Disease Outcomes Quality Initiative ( KDOQI ) ; the Seventh Report of the Joint National Committee on Prevention , Detection , Evaluation , and Treatment of High Blood Pressure ( JNC 7 ) ; and the American Diabetes Association ( Table 1 ) ( 8 , 1012 ) . We also examined the representation of older adults in relevant major trials whose results were published after guideline preparation . Second , we compared the characteristics of participants in guideline trials with those of a representative sample of older adults with chronic kidney disease from the general population enrolled in the National Health and Nutrition Examination Survey ( NHANES ) 19992006 . Table 1 . Summary of Guidelines Were Older Adults Well Represented in Trials Underpinning Major U.S. Practice Guidelines for the Use of ACE Inhibitors and ARBs in Chronic Kidney Disease ? Two co authors screened all articles referenced in the aforementioned guidelines ( Table 1 ) . When the primary article cited in the relevant guideline did not provide all prespecified data elements , we performed directed search es to identify additional publications from that study that might include this information . We restricted these search es to English- language articles published before or during the evidence review period for the most recent guideline in which the primary study was cited ( Table 1 ) . We performed these directed search es by using MEDLINE and by h and - search ing the reference lists of primary articles . When we could not identify all data elements from published sources , we requested needed information from corresponding authors . For inclusion in our review , the study was required to be an RCT in which at least 1 group was treated with an ACE inhibitor or ARB and was compared with a control group not receiving either agent . Because the rationale for all of the guidelines review ed here is that ACE inhibitors and ARBs slow progression of kidney disease , we also required that at least 1 of the following renal outcomes was reported in the article cited in the relevant guideline : change in urinary protein or albumin excretion , change in serum creatinine level , creatinine clearance , measured or estimated glomerular filtration rate ( GFR or eGFR , respectively ) , requirement for dialysis , or onset of end-stage renal disease . Two co authors separately abstract ed relevant prespecified trial characteristics , participant characteristics , and entry criteria . The guidelines referenced 37 articles describing 32 RCTs ( 6 , 1348 ) . We excluded 2 trials because the referenced article did not include a renal outcome measure ( 45 , 46 ) and 3 trials because they lacked a comparison with a control group not receiving an ACE inhibitor or ARB ( 44 , 47 , 48 ) ( Table 1 ) . We included the remaining 27 trials ( total participants , 15794 ) ( Appendix Table 1 ) . Appendix Table 1 . Baseline Participant Characteristics and Entry Criteria of Guideline Trials The mean age of trial participants ranged from 29 to 71 years . The maximum age of participants could not be ascertained in 2 trials . Among the remaining trials , 19 ( 76 % ) either excluded or did not include participants older than 70 years . No trial provided information on the number and characteristics of participants older than 70 years . Although most trials did not enroll older participants , the 5662 participants in ALLHAT ( Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial ) ( 30 ) with an eGFR less than 60 mL/min per 1.73 m2 had a mean age of 71 years , indicating that this trial enrolled a substantial number of persons older than 70 years . With the notable exception of ALLHAT , older adults were poorly represented in most guideline trials . What Were the Other Characteristics of Participants in Guideline Trials ? Most trials ( 70 % ) enrolled only participants with diabetes . Six trials were limited to those with type 1 diabetes ( n= 775 ) , 12 trials were limited to those with type 2 diabetes ( n= 6840 ) , and 1 trial included participants with either type 1 or type 2 diabetes ( n= 103 ) . Two trials included participants both with and without diabetes ( n= 6245 ) . The remaining 6 trials were conducted among participants without diabetes ( n= 1831 ) . Hypertension was an entry requirement for most trials . Female participants ranged from 23 % to 70 % across trials . Urinary protein excretion of at least 30 mg/d or equivalent was an entry criterion for 79 % of trials in persons with diabetes . Only 1 trial that included participants without diabetes explicitly required a minimum level of proteinuria . Nevertheless , mean urinary protein excretion at baseline exceeded 500 mg/d in most trials of nondiabetic chronic kidney disease . The only trial not to ascertain urinary protein level was ALLHAT , which included participants both with and without diabetes . In summary , most guideline trials were conducted among participants with diabetes and most favored inclusion of participants with proteinuria . Are Older Adults Well Represented in Recent Trials Comparing the Effect of ACE Inhibitors or ARBs With That of Other Agents on Progression of Chronic Kidney Disease ? We conducted a MEDLINE search from 1 July 2002 through 31 December 2008 to identify the results of major trials published after the most recent review date s for the 2004 KDOQI guideline ( for studies of nondiabetic kidney disease ) and the 2007 KDOQI guideline ( for studies of diabetic kidney disease ) . We limited our search to English- language publications , human studies , and RCTs . One coauthor review ed all titles , and abstract s and manuscripts as needed , to identify eligible studies . We included only RCTs that compared the effect of ACE inhibitors or ARBs with a control group not receiving either agent , enrolled more than 200 participants , and included at least 1 renal outcome measure . We excluded trials in specialized population s ( for example , patients receiving dialysis , kidney transplant recipients , and patients with heart failure ) . Two co authors separately abstract ed prespecified baseline participant characteristics and exclusion criteria for eligible trials . We identified 380 MEDLINE citations , obtained 68 articles for further review , and identified 6 eligible trials ( Appendix Table 2 ) ( 4954 ) . Only 1 trial did not enroll participants older than 70 years . Mean participant age ranged from 45 to 63 years across trials . All but 1 trial included participants without diabetes . Only 2 trials ( 49 , 54 ) included a substantial number of participants without microalbuminuria or macroalbuminuria . Dagenais and colleagues ( 49 ) r and omly assigned 5269 adults age 30 years or older with glucose intolerance and without clinical proteinuria to receive ramipril or placebo . The composite renal outcome ( increase in proteinuria , decrease in eGFR 30 % , or dialysis or transplantation ) did not differ between groups over a 3-year follow-up . Vogt and colleagues ( 54 ) r and omly assigned 614 adults to receive telmisartan , hydrochlorothiazide , or placebo . Most participants did not have diabetes  , and only 25 % had microalbuminuria or macroalbuminuria . Over a 6-week follow-up , urinary albumin excretion decreased to the greatest extent in the group receiving telmisartan . Change in creatinine clearance did not differ across groups . Our OBJECTIVE Angiotensin-converting enzyme inhibitor ( ACEI ) is beneficial in patients with congestive heart failure ( CHF ) . Some , but not all , angiotensin receptor blocker ( ARB ) was demonstrated to be effective as " add-on " therapy . We investigated whether irbesartan is useful as an add-on therapy in CHF . DESIGN R and omized control trial . SETTING Single center . PATIENTS 50 CHF patients on stable doses of ACEI . INTERVENTIONS Add-on therapy with irbesartan ( 300 mg/day ) or continuation of conventional therapy ( control group ) for 1 year . MAIN OUTCOME MEASURES Serial clinical and echocardiographic assessment were performed as baseline , 3 months and 1 year after therapy . RESULTS There was no difference in clinical characteristics between 2 groups . Patients in the add-on therapy group had significant increase in 6-Minute Hall-Walk distance ( 351+/-89 to 392+/-84 m , P<0.01 ) , achieved higher METs exercise time on treadmill test ( 3.9+/-1.1 to 4.6+/-1.3 METs , P=0.01 ) , reduction of NYHA Class ( 2.4+/-0.5 to 2.0+/-0.8 , P<0.005 ) and improvement of QOL score ( 28+/-19 to 17+/-18 , P<0.05 ) . These parameters were not improved in the control group and a worsening of exercise capacity was observed ( P<0.05 ) . A reduction of left ventricular end-systolic diameter ( 4.94+/-0.85 vs 4.30+/-1.17 cm , P<0.05 ) was observed in the add-on group . At the end of 1 year , more patients have normal or abnormal relaxation pattern in the add-on group than the control group ( 82 % vs 53 % chi(2)=7.1 , P=0.02 ) . Blood pressure and renal function were unchanged in both groups . CONCLUSION The addition of irbesartan to conventional ACEI therapy in CHF further improves symptoms , exercise capacity and quality of life without adverse effects on hemodynamics and renal function 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 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 OBJECTIVE Evidence suggests that the effectiveness of angiotensin-converting enzyme ( ACE ) inhibition diminishes with time , result ing in increasing angiotensin II levels , the action of which can be inhibited by the addition of an angiotensin receptor blocker ( ARB ) . In the present study , the renal protective effects of ACE inhibitors and ARBs were compared over a five-year period in a prospect i ve , r and omized , open-blind study in 68 nondiabetic Japanese patients with elevated serum creatinine levels . PATIENTS AND METHODS Japanese patients with renal insufficiency were r and omly assigned to receive either an  ACE inhibitor ( benazepril 1.25 to 5 mg daily or tr and olapril 0.5 to 4 mg daily ) or ARB ( c and esartan 2 to 8 mg daily or losartan 25 to 100 mg daily )  at the Kidney Disease Center at Saitama Medical School Hospital . The primary study endpoint was a change in glomerular filtration rate ( GFR ) between the baseline value and the last available value obtained during the five-year treatment period , as estimated by the Cockcraft-Gault equation . Secondary endpoints included the annual changes in GFR , serum creatinine level , urinary protein excretion , and blood pressure , as well as the rate of development of endstage renal disease . RESULTS There were no significant differences in the primary endpoint between the two groups . However , after 4 years , the decline in GFR in patients treated with ARBs was significantly greater than that seen in patients treated with an ACE inhibitor ( p<0.05 ) . Furthermore , the rate of introduction of dialysis therapy was also significantly greater in the ARB-treated patients ( 52.7 % in ACE inhibitor and 81.2 % in ARB group at year 5 . p<0.01 ) . CONCLUSION While our data suggested that ARB , like ACE , treatment might slow the progression of renal dysfunction , it also pointed to the necessity to be alerted to the progression to endstage renal disease with longterm medication
Our analyses found no evidence of a difference in total mortality or cardiovascular outcomes for ARBs as compared with ACE inhibitors , while ARBs caused slightly fewer WDAEs than ACE inhibitors .
Although ACE inhibitors have shown efficacy in these outcomes over placebo , our results can not be used to extrapolate the same conclusion for ARBs directly , which have not been studied in placebo-controlled trials for hypertension .
BACKGROUND Angiotensin converting enzyme inhibitors ( ACE inhibitors ) and angiotensin receptor blockers ( ARBs ) are widely prescribed for primary hypertension ( systolic blood pressure > 140 mmHg or diastolic blood pressure > 90 mmHg ) .
However , while ACE inhibitors have been shown to reduce mortality and morbidity in placebo-controlled trials , ARBs have not .
Therefore , a comparison of the efficacies of these two drug classes in primary hypertension for preventing total mortality and cardiovascular events is important .
OBJECTIVES To compare the effects of ACE inhibitors and ARBs on total mortality and cardiovascular events , and their rates of withdrawals due to adverse effects ( WDAEs ) , in people with primary hypertension .