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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

NICE first issued guidance for the management of hypertension in primary care in 2004. This was followed by a rapid update of the pharmacological treatment chapter of the guideline in 2006. The current partial update of the hypertension guideline is in response to the regular five year review cycle of existing NICE guidance. It began with a scoping exercise which identified key areas of the existing guideline for which new evidence had emerged that was likely to influence or change existing guideline recommendations.

NICE Clinical Guidelines - National Clinical Guideline Centre (UK).

Version: August 2011

Angina is pain or constricting discomfort that typically occurs in the front of the chest (but may radiate to the neck, shoulders, jaw or arms) and is brought on by physical exertion or emotional stress. It is the main symptomatic manifestation of myocardial ischaemia and is usually caused by obstructive coronary artery disease restricting oxygen delivery to the cardiac myocytes. Other factors may exacerbate angina either by further restricting oxygen delivery (for example severe anaemia) or by increasing oxygen demand (for example left ventricular hypertrophy). Angina symptoms are associated with other cardiac disease such as aortic stenosis but the management of angina associated with non-coronary artery disease is outside the scope of this guideline.

NICE Clinical Guidelines - National Clinical Guidelines Centre (UK).

Version: July 2011

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

Hypertension in children can be associated with adverse health outcomes and may persist into adulthood, where it presents a significant personal and public health burden. Screening asymptomatic children has the potential to detect hypertension at earlier stages, so that interventions can be initiated which, if effective, could reduce the adverse health effects of childhood hypertension in children and adults.

Evidence Syntheses - Agency for Healthcare Research and Quality (US).

Version: February 2013

To evaluate the comparative effectiveness of interventions (intravenous [IV] fluids, N-acetylcysteine, sodium bicarbonate, and statins, among others) to reduce the risk of contrast-induced nephropathy (CIN), need for renal replacement therapy, mortality, cardiac complications, prolonged length of stay, and other adverse events after receiving low-osmolar contrast media (LOCM) or iso-osmolar contrast media (IOCM).

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

Version: January 2016

The Renal National Service Framework (NSF), and the subsequent NICE Clinical Practice Guideline for early identification and management of adults with chronic kidney disease (CKD) in primary and secondary care (CG73), served to emphasise the change in focus in renal medicine from treatment of established kidney disease to earlier identification and prevention of kidney disease.

NICE Clinical Guidelines - National Clinical Guideline Centre (UK).

Version: July 2014

Hypertension is a very common chronic illness in the United States and among Veterans. Use of antihypertensive medications can lower the risk of cardiovascular disease, cerebrovascular disease, renal disease, and death. The most beneficial blood pressure targets for patients of specific age groups, however, has been a topic of some debate and controversy, stemming from concerns that the ratio of benefit to harm of a given blood pressure level may vary with age. In 2014, the Joint National Committee on the Prevention, Detection, Evaluation, and Treatment of High Blood Pressure (previously JNC-FG8, referred to in this report as JNC-BP) published new guidelines for the treatment of hypertension, as well as a new treatment goal for older individuals (over age 60) for systolic blood pressure (SBP) of < 150 mm Hg rather than < 140 mm Hg. The new goal for those over 60 years of age has been very controversial; the issue of the appropriate (safest and most beneficial) goal for older people has been debated among experts with viewpoints supporting both higher and lower treatment goals. The objectives of this review are to examine the benefits and harms of differing blood pressure targets among adults over age 60.

Evidence-based Synthesis Program - Department of Veterans Affairs (US).

Version: April 2016

This generally well-conducted review concluded that available evidence suggested intensive blood pressure control (135mmHg or lower) reduced the risk of macrovascular events (death or stroke) in participants with type 2 diabetes mellitus/impaired fasting glucose or glucose intolerance, but increased the risk of serious adverse events. 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: 2011

The review concluded that the results suggested patients with hypertension treated with calcium channel blockers had an increased incidence of heart failure, but that this effect should be researched further. Despite some potential limitations with the review process, and uncertain definitions of heart failure in the included trials (noted by the authors), the authors’ cautious conclusions reflect the evidence presented.

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

Version: 2010

This review concluded that fixed-dose combinations of antihypertensive agents were associated with a significant improvement in compliance and with non significant beneficial trends in blood pressure and adverse effects. These conclusions were supported by the data presented, but their reliability is unclear due to limitations in the quality assessment.

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

Version: 2010

The authors concluded that angiotensin converting-enzyme inhibitor/angiotensin II receptor blocker agents appeared to improve proteinuria and have a protecting effect on renal function. Given potential sources of bias that included methodological variability, inclusion of studies with small samples sizes and use concomitant medication by participants, the authors' conclusions should be treated with caution.

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

Version: 2009

This review concluded that there was insufficient evidence to determine the effects of angiotensin-converting enzyme inhibitors and angiotensin-receptor blockers on mortality or cardiovascular events in people on peritoneal dialysis; limited evidence may show some positive effect on renal function. The review was well conducted and the conclusions were appropriate given the limited amount of available data from small studies.

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

Version: 2009

This review found that fixed-dose combination medications increase medication compliance, compared with free-drug regimens, in patients with chronic conditions. Although the data appear to support these conclusions, they should be interpreted with some degree of caution because of limitations in the search and a failure to assess study quality.

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

Version: 2007

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