Angiotensin Converting Enzyme Inhibitors Aceis Angiotensin Ii Receptor Antagonists Arbs And Direct Renin Inhibitors For Treating Essential Hypertension

Almost 75 million American adults-approximately one-third-have hypertension. The prevalence of hypertension increases with advancing age such that more than half of people 55 to 74 years old and approximately three-fourths of those age 75 years and older are affected. In addition to being the primary attributable risk factor for death throughout the world, hypertension results in substantial morbidity because of its impact on numerous target organs, including the brain, eyes, heart, arteries, and kidneys. Despite the high rates of morbidity and mortality attributable to hypertension, control of the condition remains suboptimal. In addition to several effective nonpharmacological interventions-including diet, exercise, and control of body weight-many people require antihypertensive medication to lower blood pressure. Among the many choices in antihypertensive therapy, some of the most common are those aimed at affecting the renin-angiotensin-aldosterone (renin) system. The renin system is an important mediator of blood volume, arterial pressure, and cardiac and vascular function. Components of this system can be identified in many tissues, but the primary site of renin release is the kidney. The renin system can be triggered by sympathetic stimulation, renal artery hypotension, and decreased sodium delivery to the distal tubule. Through proteolytic cleavage, renin acts on the oligopeptide substrate angiotensinogen to produce the decapeptide angiotensin I. In turn, two terminal peptide residues of angiotensin I are removed by the angiotensinconverting enzyme (ACE) to form the octapeptide angiotensin II. Angiotensin II acts directly on the resistance vessels to: increase systemic vascular resistance and arterial pressure; stimulate the adrenal cortex to release aldosterone, which leads to increased sodium and water reabsorption and potassium excretion; promote secretion of antidiuretic hormone, which leads to fluid retention; stimulate thirst; promote adrenergic function; and increase cardiac and vascular hypertrophy. Therapies aimed at modifying the renin system have been used extensively for treatment of hypertension, heart failure, myocardial infarction, diabetes, and renal disease. Currently, three classes of drugs that interact with this system are used to inhibit the effects of angiotensin II: the angiotensin-converting enzyme inhibitors (ACEIs), the angiotensin II receptor blockers/antagonists (ARBs), and the direct renin inhibitors. ACEIs block the conversion of angiotensin I into angiotensin II; ARBs selectively inhibit angiotensin II from activating the angiotensin-specific receptor (AT1); and direct renin inhibitors block the conversion of angiotensinogen into angiotensin I. This review summarizes the evidence on the comparative long-term benefits and harms of ACEIs, ARBs, and direct renin inhibitors, focusing on their use for treating essential hypertension in adults. In that analysis, investigators assessed the conclusions from the original comparative effectiveness review, performed a limited literature search of potentially new evidence, and solicited expert opinions concerning the state of the evidence and validity of the original report. Key Questions addressed are: Key Question 1. For adult patientsa with essential hypertension, how do ACEIs (angiotensin-converting enzyme inhibitors), ARBs (angiotensin II receptor antagonists), and direct renin inhibitorsb differ in blood pressure control, cardiovascular risk reduction, cardiovascular events, quality of life, and other outcomesc? Key Question 2. For adult patients with essential hypertension, how do ACEIs, ARBs, and direct renin inhibitors differ in safety, adverse events, tolerability, persistence with drug therapy, and treatment adherence

Almost 75 million American adults have hypertension. Advances in antihypertensive therapy have dramatically reduced cardiovascular, cerebrovascular, and renal events. Among the effective pharmacotherapies are inhibitors of the renin-angiotensin-aldosterone system (RAS). In 2007, the Agency for Healthcare Research and Quality (AHRQ) sponsored a comparative effectiveness review (CER) of the two most common renin system inhibitors, angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin receptor blockers (ARBs), to answer the following three Key Questions for adults with essential hypertension: do ACEIs and ARBs differ in their (1) blood pressure control, cardiovascular events, quality of life, and other outcomes; (2) safety, tolerability, persistence with therapy, or treatment adherence; and (3) effects within important subgroups of patients? This 2007 CER was updated in 2011 to incorporate the significant additional direct comparison research published in the interval and to include direct renin inhibitors (DRIs), which are the newest class of RAS inhibitors. The results of the updated CER included 97 studies (36 new since 2007) directly comparing ACEIs versus ARBs and 3 studies directly comparing DRIs to ACEIs or ARBs. The strength of evidence remained high for equivalence between ACEIs and ARBs for blood pressure lowering, and for superiority of ARBs over ACEIs for short-term adverse events (primarily cough). The new evidence did not strengthen the conclusions regarding long-term cardiovascular outcomes, quality of life, progression of renal disease, medication adherence or persistence, rates of angioedema, or differences in key patient subgroups; the strength of evidence for these outcomes remained low to moderate. Evidence on the comparative effectiveness of DRIs versus either ACEIs or ARBs was limited to 3 studies with 2,049 patients and did not allow definitive conclusions on any of the included outcomes. Few studies involved a representative patient sample treated in a typical clinical setting over a long duration; treatment protocols had marked heterogeneity; and significant amounts of data about important outcomes and patient subgroups were missing. Given the clinical and economic importance of these medications, the ongoing investment in research, and the remaining areas of uncertainty, we sought to create a prioritized research agenda representing the interests of diverse stakeholders in order to address the remaining areas of uncertainty.

The relationship between angiotensin II and hypertension was established in 1898 when angiotensin II was shown to modulate systemic blood pressure. Over the intervening decades, a complete characterization of the renin-angiotensin system (RAS) has been achieved, and our understanding of its biochemistry and physiology has led to the directed development of agents such ·as ACE inhibitors and receptor antagonists capable of controlling hypertension. More recently, it was shown that angiotensin II is secreted within certain tissues and that these tissue-specific systems operate independently of the systemic RAS. The novel concept that angiotensin II regulates a number of cardiovascular processes that are unrelated to blood pressure has renewed the interest of both basic and clinical scientists in angiotensin II. The association between angiotensin II and cardiac growth, in particular, has indicated that therapies currently in use for hypertension may have direct application to the treatment of heart failure. The Manitoba Cardiovascular Forum on Angiotensin Receptor Blockade in Winnipeg was convened October 18-20, 1996 to examine the clinical and basic aspects of angiotensin receptor biology as they apply to hypertension and heart failure. In addition, the potential treatment of these conditions using specific angio tensin receptor antagonists was addressed within the context of their immediate therapeutic application and future potential.

Diabetes and hypertension have evolved as two of the modern day epidemics affecting millions of people around the world. These two common co-morbidities lead to substantial increase in cardiovascular disease, the major cause of morbidity and mortality of adults around the world. In Diabetes and Hypertension: Evaluation and Management, a panel of renowned experts address a range of critical topics -- from basic concepts in evaluation and management of diabetes and hypertension, such as dietary interventions, to evaluation and management of secondary hypertension in clinical practice. Other chapters focus on high cardiovascular risk populations such as those with coronary heart disease, chronic kidney disease and minority patients. In addition, evolving concepts and new developments in the field are presented in other chapters, such as prevention of type 2 diabetes and the epidemic of sleep apnea and its implication for diabetes and hypertension evaluation and management. An important title covering two of the most troubling disorders of our time, Diabetes and Hypertension: Evaluation and Management will provide the busy practitioner with cutting edge knowledge in the field as well as practical information that can translate into better care provided to the high-risk population of diabetics and hypertensive patients.

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Here is an extensive update of Pediatric Nephrology, which has become the standard reference text in the field. It is global in perspective and reflects the international group of editors, who are well-recognized experts in pediatric nephrology. Within this text, the development of kidney structure and function is followed by detailed and comprehensive chapters on all childhood kidney diseases.

The Encyclopedia of Heart Diseases is an accurate and reliable source of in-depth information on the diseases that kill more than 12 million individuals worldwide each year. In fact, cardiovascular diseases are more prevalent than the combined incidence of all forms of cancer, diabetes, asthma and leukemia. In one volume, this Encylopedia thoroughly covers these ailments and also includes in-depth analysis of less common and rare heart conditions to round out the volume's scope. Researchers, clinicians, and students alike will all find this resource an invaluable tool for quick reference before approaching the primary literature. * Coverage of more than 200 topics, including: applied pharmacology of current and experimental cardiac drugs, gene therapy, MRI, electron-beam CT, PET scan put in perspective, cardiac tests costs and justification, and new frontiers in cardiovascular research * More than 150 helpful figures and illustrations! * Dr. Khan is a well-published and respected expert in heart and heart diseases