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Drug Class Review: Direct Renin Inhibitors, Angiotensin Converting Enzyme Inhibitors, and Angiotensin II Receptor Blockers: Final Report [Internet]

The renin-angiotensin system is a complex biologic system between the heart, brain, blood vessels, and kidneys that leads to the production of biologically active agents, including angiotensin I and II and aldosterone, which act together to impact a variety of bodily functions including blood vessel tone, sodium balance, and glomerular filtration pressure. The multiple and varied effects of these agents allows the renin-angiotensin system to play a wide role in the pathology of hypertension, cardiovascular health, and renal function. Our ability to begin to intervene upon the complex cycle of hormone and other biochemical agent production within the renin-angiotensin system began with the advent of the first orally active ACE-I (angiotensin converting enzyme inhibitor), captopril, in 1981. AIIRAs (angiotensin II receptor blockers) were developed as an alternative to ACE-I, and block the interaction between angiotensin II and the angiotensin receptor. Losartan, the first commercially available AIIRA, was approved for clinical use in 1995. The goal of this report is to compare the effectiveness and harms between aliskiren and placebo and between AIIRAs and ACEIs in the treatment of diagnosed coronary heart disease, hypertension, left ventricular dysfunction, heart failure, nondiabetic chronic kidney disease, or diabetic nephropathy.

Drug Class Reviews - Oregon Health & Science University.

Version: January 2010
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Are angiotensin receptor blockers (ARBs) an effective treatment for heart failure?

Drugs called angiotensin receptor blockers (ARBs), such as losartan (brand name: Cozaar), candesartan (Atacand), eprosartan (Teveten), irbesartan (Avapro), telmisartan (Micardis) and valsartan (Diovan) are commonly used to treat heart failure. We asked whether ARBs reduced death, or severe disability as assessed by hospital admission for any reason versus an inert substance (placebo) or another class of drugs called ACE inhibitors, such as ramipril (Altace), captopril (Capoten), enalapril (Vasotec), fosinopril (Monopril), lisinopril (Prinivil, Zestril), and quinapril (Accupril). We also asked whether combining an ARB with an ACE inhibitor is more effective than an ACE inhibitor alone in reducing death, disability, or hospital admission for any reason. The scientific literature was searched to find all trials that had assessed these questions.

Cochrane Database of Systematic Reviews: Plain Language Summaries [Internet] - John Wiley & Sons, Ltd.

Version: 2012

Angiotensin-Converting Enzyme Inhibitors (ACEIs), Angiotensin II Receptor Antagonists (ARBs), and Direct Renin Inhibitors for Treating Essential Hypertension: An Update [Internet]

A 2007 comparative effectiveness review (CER) evaluated the long-term benefits and harms of angiotensin-converting enzyme inhibitors (ACEIs) versus angiotensin II receptor blockers/antagonists (ARBs) for treating essential hypertension in adults. Since then, significant additional research has been published comparing these agents, and direct renin inhibitors (DRIs) have been introduced to the market. We sought to update 2007 CER on ACEIs versus ARBs and expand this to include comparisons with DRIs.

Comparative Effectiveness Reviews - Agency for Healthcare Research and Quality (US).

Version: June 2011
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Angiotensin‐converting enzyme inhibitors and angiotensinII receptor blockers for preserving residual kidney function in peritoneal dialysis patients

Residual kidney function plays a key role in the health and quality of life of patients on peritoneal dialysis (PD). Better preservation of residual kidney function is associated with decreased mortality, even at 1 mL/min of residual glomerular filtration rate (GFR), which is associated with a nearly 50% reduction in mortality rate. Two kinds of antihypertensive drugs, angiotensin‐converting enzyme inhibitors (ACEis) and angiotensinII receptor blockers (ARBs), are frequently prescribed for PD patients (primarily to control hypertension or heart failure), and could provide significant cardiovascular benefit for ESKD patients. Nowadays, while ACEis and ARBs use is advocated in PD patients, the supporting evidence is still unclear. However studies have focused on heart protection rather than residual kidney function. The aim of this review was to assess the benefits and harms of ACEis and ARBs therapy for preserving residual kidney function in PD patients. Six studies (257 patients) were included (three ARB studies, one ACEi study and ACEi versus ARB studies). Long‐term use (12 months or more) of an ARB showed a significant benefit in preserving residual kidney function in continuous ambulatory PD (CAPD) patients compared with other antihypertensive drugs, although there was no significant benefit when an ARB were used for less than six months). One study showed that compared with other antihypertensive drugs, long‐term use of the ACEi ramipril showed a significant reduction in the decline of residual kidney function in patients on CAPD as well as anuria rate. While dizziness and cough are the main adverse events when an ACEi is used, only one study comparing an ARB with an ACEi reported this outcome and no significant difference between the two groups were found. While the use of an ARB or an ACEi may both be useful in preserving residual kidney function, the small number of studies and small number of patients enrolled means there is currently insufficient evidence to support the use of an ACEi or an ARB as first line antihypertensive therapy in PD patients.

Cochrane Database of Systematic Reviews: Plain Language Summaries [Internet] - John Wiley & Sons, Ltd.

Version: 2014

Literature search on angiotensin-II antagonists and ACE inhibitors: Executive summary of working paper A10-04

The aim of the present literature search was to identify long-term studies investigating AT-II antagonists and ACE inhibitors in therapeutic areas approved for AT-II antagonists and comparing the drug classes with each other and with placebo.

Institute for Quality and Efficiency in Health Care: Executive Summaries [Internet] - Institute for Quality and Efficiency in Health Care (IQWiG).

Version: April 18, 2011

Optimal strategies for identifying kidney disease in diabetes: properties of screening tests, progression of renal dysfunction and impact of treatment – systematic review and modelling of progression and cost-effectiveness

This study found evidence to support the use of annual screening to identify the development of early kidney disease in patients with diabetes, which is consistent with current UK guidelines. For type 1 diabetes, the costs of annual screening are well within the accepted level of cost-effectiveness, and, for patients with type 2 diabetes, annual screening is even more cost-effective.

Health Technology Assessment - NIHR Journals Library.

Version: February 2014
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Aldosterone antagonists for preventing the progression of chronic kidney disease

People who have chronic kidney disease (CKD) are at increased risk of heart disease and worsening kidney disease needing treatment with dialysis or a kidney transplant. Increased amounts of protein in the urine are a sign of kidney stress and are linked to a greater chance of worsening kidney function. Treatments that lower urine protein levels and protect kidney function are available and include angiotensin‐converting enzyme inhibitors and angiotensin receptor blockers. However, protection of kidney function with these two drugs may be incomplete and adding aldosterone blockers (for example, spironolactone or eplerenone) may better protect kidney function. The use of numerous drugs may also increase side‐effects. This review of available trials showed that adding aldosterone antagonist treatment to standard therapy reduced protein release into the urine and lowered blood pressure but had uncertain effects on kidney function and survival. Treatment also increases the amount of potassium in the blood which may require treatment changes, extra blood tests and is potentially harmful. Whether aldosterone blockers protect kidney function to lower the chances needing dialysis or kidney transplantation or prevent heart disease in people who have CKD is unclear and not answered by existing research.

Cochrane Database of Systematic Reviews: Plain Language Summaries [Internet] - John Wiley & Sons, Ltd.

Version: 2014

[Effect of angiotensin-converting enzyme inhibitors and angiotensin II receptor blockers on all-cause mortality, cardiovascular deaths, and cardiovascular events in patients with diabetes mellitus. A meta-analysis]

Bibliographic details: Divison Garrote JA, Segui Diaz M, Escobar Cervantes C.  [Effect of angiotensin-converting enzyme inhibitors and angiotensin II receptor blockers on all-cause mortality, cardiovascular deaths, and cardiovascular events in patients with diabetes mellitus. A meta-analysis]. [Efecto de inhibidores de la enzima conversora y bloqueantes del receptor de angiotensina ii en todas las causas de mortalidad, mortalidad cardiovascular y eventos cardiovasculares en pacientes con diabetes. Un metaanalisis.] Semergen 2014; 40(7): 399-40025103068

Database of Abstracts of Reviews of Effects (DARE): Quality-assessed Reviews [Internet] - Centre for Reviews and Dissemination (UK).

Version: 2014

Angiotensin converting enzyme inhibitors and angiotensin II receptor antagonists for preventing the progression of diabetic kidney disease

Kidney disease develops in 25% to 40% of diabetic patients, usually 20 to 25 years after the onset of diabetes. Approximately one third of those with diabetic kidney disease (DKD) will progress to end‐stage kidney disease (ESKD) and will require long‐term dialysis or possibly receive a kidney transplant. Many patients however may die from associated coronary artery disease or other cardiovascular causes before the onset of ESKD. Antihypertensive drugs have been shown to not only be of benefit to the heart but to also provide kidney protection by slowing the progression of DKD to ESKD. Two drugs in particular have been considered equally effective for patients with DKD ‐ these are angiotensin converting enzyme inhibitors (ACEi) and angiotensin II receptor antagonists (AIIRA). However studies have focused on kidney protection rather than over mortality. The aim of this review was to assess the benefits and harms or ACEI and AIIRA therapy in patients with DKD. Fifty studies (13,215 patients) were identified comparing ACEi to placebo, AIIRA to placebo and ACEi to AIIRA. The risk of death from any cause was not significantly reduced with the use of ACEi versus placebo, AIIRA versus placebo or ACEi versus AIIRA. However when we looked at the studies which used the maximum dose tolerated of ACEi rather than the lower, so‐called renal doses, there was a significant reduction in the risk of death due to any cause. We were unable to determine which drug provides better protection due to the lack of head‐to‐head trials.

Cochrane Database of Systematic Reviews: Plain Language Summaries [Internet] - John Wiley & Sons, Ltd.

Version: 2010

Meta-analysis-based examination regarding the efficacy of angiotensin II receptor blockers and calcium channel blockers in borderline diabetes and diabetes patients

We performed a meta-analysis to assess antihypertensive effect, lipid metabolism, insulin resistance index, and body weight changes in patients with borderline diabetes and diabetes treated with angiotensin II receptor blockers (ARB) and dihydropyridine calcium channel blockers (CCB). Literatures for analysis were searched in MEDLINE, the Cochrane Library, and Japana Centra Revuo Medicina. Reports on randomized controlled trials in which the therapeutic results in borderline and diabetic patients were compared between those treated with ARB and CCB were retrieved, and 16 reports met the objective of this study. The efficacy in the two drug treatment groups were divided into 8 outcomes and evaluated. The efficacy outcomes on handling continuous data were integrated using the weighted mean difference, in which the random-effects model was selected for the statistical model. The statistical heterogeneity of each outcome was also tested. The systolic and diastolic blood pressures were significantly reduced in the CCB compared to the ARB treatment group. No significant differences were noted between the two groups in the triglyceride or low-density lipoprotein cholesterol level or body weight changes. It was shown that the CCB was more effective than ARB for the improvement of systolic and diastolic blood pressures in patients with borderline diabetes and diabetes, while no significant differences were noted in the efficacy other than the antihypertensive effect between ARB and CCB treatment groups. This study would provide information in selecting antihypertensive agents for borderline and diabetic patients.

Database of Abstracts of Reviews of Effects (DARE): Quality-assessed Reviews [Internet] - Centre for Reviews and Dissemination (UK).

Version: 2011

Role of antihypertensive therapy with angiotensin-converting enzyme inhibitors or angiotensin II receptor blockers in combination with calcium channel blockers for stroke prevention

OBJECTIVE: To review the available literature on the effects of angiotensin-converting enzyme inhibitors (ACEIs), angiotensin II receptor blockers (ARBs), and calcium channel blockers (CCBs) or combinations of these agents on stroke outcomes in hypertensive patients.

Database of Abstracts of Reviews of Effects (DARE): Quality-assessed Reviews [Internet] - Centre for Reviews and Dissemination (UK).

Version: 2010

Meta-analysis of combined therapy with angiotensin receptor antagonists versus ACE inhibitors alone in patients with heart failure

This review concluded that angiotensin II receptor blockers added to angiotensin-converting enzyme inhibitor therapy did not reduce mortality in people with heart failure and were associated with a reduction in hospitalisation for heart failure, but not overall hospitalisation. There was an increase in adverse events. The review appeared well conducted and the authors’ conclusions are likely to be reliable.

Database of Abstracts of Reviews of Effects (DARE): Quality-assessed Reviews [Internet] - Centre for Reviews and Dissemination (UK).

Version: 2010

Angiotensin‐converting enzyme inhibitors and angiotensin receptor blockers for adults with early chronic kidney disease who do not have diabetes

Chronic kidney disease (CKD) is a long‐term condition that occurs as a result of the kidneys being damaged. Progressive deterioration of kidney function can lead to end‐stage kidney disease (ESKD). People with ESKD cannot maintain healthy kidney function and need kidney dialysis or transplant. In the early stages of CKD, patients may not have any outward symptoms or signs of illness, and may only be detected following investigations such as urine or blood testing. Two types of drugs ‐ angiotensin‐converting enzyme inhibitors (ACEi) and angiotensin receptor blockers (ARB) ‐ have been widely recommended in clinical guidelines for doctors to use in the management of CKD. This review identified four studies (enrolling 2177 people). Three studies compared ACEi to placebo or no treatment and one study compared ACEi to ARB. There is not enough evidence in the published literature at present to determine how effective drugs in the ACEi or ARB families are for treating patients with early (stage 1 to 3) CKD who do not have diabetes.

Cochrane Database of Systematic Reviews: Plain Language Summaries [Internet] - John Wiley & Sons, Ltd.

Version: 2011

A meta-analysis of the effect and safety of angiotensin II receptor blockers in treatment of portal hypertension in cirrhotic patients

OBJECTIVE: To evaluate the efficacy and safety of the angiotensin II receptor blockers (ARB) in reducing portal hypertension (PHT) in patients with cirrhosis.

Database of Abstracts of Reviews of Effects (DARE): Quality-assessed Reviews [Internet] - Centre for Reviews and Dissemination (UK).

Version: 2011

Non‐immunosuppressive treatment for IgA nephropathy

IgA nephropathy (IgAN) is the most common primary glomerular disease with approximately 30% to 40% of patients progressing to end‐stage kidney disease (ESKD) within 20 years. The most common regimens include immunosuppressive agents, however the risks of long‐term treatment often outweigh the potential benefits. Non‐immunosuppressive options, including fish oils, anticoagulants, antihypertensive agents and tonsillectomy have also been examined but not reviewed systematically.

Cochrane Database of Systematic Reviews: Plain Language Summaries [Internet] - John Wiley & Sons, Ltd.

Version: 2011

Drugs for preventing kidney disease in people with diabetes

Many people with diabetes (around 20% to 60%) are are affected by high blood pressure (hypertension) and need drugs (antihypertensive agents) to treat this condition. These drugs also help to prevent development of kidney disease both in people with diabetes who have normal blood pressure and those whose blood pressure is high. Many people with diabetic kidney disease (DKD) (20% to 40%) go on to develop end‐stage kidney disease (ESKD), and many others die from heart disease or other circulatory problems before ESKD develops.

Cochrane Database of Systematic Reviews: Plain Language Summaries [Internet] - John Wiley & Sons, Ltd.

Version: 2013

Beta‐blockers for hypertension

The aim of this Cochrane Review was to assess whether beta‐blockers decrease the number of deaths, strokes, and heart attacks associated with high blood pressure in adults. We collected and analysed all relevant studies to answer this question and found 13 relevant studies.

Cochrane Database of Systematic Reviews: Plain Language Summaries [Internet] - John Wiley & Sons, Ltd.

Version: 2017

Effect of angiotensin-converting enzyme inhibitors and angiotensin II receptor blockers on all-cause mortality, cardiovascular deaths, and cardiovascular events in patients with diabetes mellitus: a meta-analysis

The authors concluded that ACEIs reduced all-cause mortality, cardiovascular mortality and major cardiovascular events in patients with diabetes mellitus whereas ARBs had no beneficial effects on these outcomes. These conclusions reflect the evidence presented and appear reliable.

Database of Abstracts of Reviews of Effects (DARE): Quality-assessed Reviews [Internet] - Centre for Reviews and Dissemination (UK).

Version: 2014

Adverse effects of combination angiotensin II receptor blockers plus angiotensin-converting enzyme inhibitors for left ventricular dysfunction: a quantitative review of data from randomized clinical trials

This review, which evaluated the safety of combination angiotensin II-receptor blockers (ARBs) plus angiotensin-converting enzyme (ACE) inhibitors in symptomatic left ventricular dysfunction, concluded that ARB plus ACE inhibitor therapy is associated with a significant increase in the risks of medication nonadherence, renal dysfunction and symptomatic hypotension. The authors' conclusions reflect the evidence presented but are based on only four trials.

Database of Abstracts of Reviews of Effects (DARE): Quality-assessed Reviews [Internet] - Centre for Reviews and Dissemination (UK).

Version: 2007

Angiotensin-converting enzyme inhibitors, angiotensin receptor blockers and combined therapy in patients with micro- and macroalbuminuria and other cardiovascular risk factors: a systematic review of randomized controlled trials

BACKGROUND: A recent clinical trial showed harmful renal effects with the combined use of angiotensin-converting enzyme inhibitors (ACEI) and angiotensin-II receptor blockers (ARB) in people with diabetes or vascular disease. We examined the benefits and risks of these agents in people with albuminuria and one or more cardiovascular risk factors.

Database of Abstracts of Reviews of Effects (DARE): Quality-assessed Reviews [Internet] - Centre for Reviews and Dissemination (UK).

Version: 2011

Systematic Reviews in PubMed

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