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Commencing Volume 19, Issue 1, MedReviews has ceased the publication of this journal. Reviews in Cardiovascular Medicine will continue to be published by IMRPress, Ltd. (www.imrpress.org)

Volume 8, Supplement 2, 2007

Volume 8, Supplement 2, 2007

Table of Contents

Expanding the Opportunities for Blocking the Renin–Angiotensin System: Introduction to a Special Supplement Introduction
The previous dogma that the renin–angiotensin system exerts its effects entirely through angiotensin II is now under challenge as scientists explore the properties of the prorenin/renin receptor and start to study local vascular actions of renin independent of its production of angiotensin in the plasma. The demonstrated blood pressure effects of the first clinically developed renin inhibitor, aliskiren, have confirmed the validity of this new class of drugs. Future research, exploring effects on the renin– angiotensin system that perhaps cannot be provided by the currently used blockers of this system, will test whether enhanced clinical benefits might result from this new pharmacologic strategy in patients at risk of cardiovascular events. [Rev Cardiovasc Med. 2007;8(suppl 2):S1-S6]
The Renin System: Is Direct Renin Inhibition Different From Blockade at the AT1 Receptor or the ACE Step? Renin Inhibition in Hypertension
A substantial level of evidence supports the use of renin system blockade for many patients with hypertension. Two lines of evidence, based on very high-dose angiotensin blocker treatment or combination therapy with angiotensin-converting enzyme inhibitor and angiotensin receptor blocker, suggest that more complete blockade leads to improved clinical outcomes. The recent development of a powerful renin inhibitor that acts at the initial, rate-limiting step in the renin cascade would also favor more complete blockade of the system. For many patients, this is likely to lead to improved treatment. [Rev Cardiovasc Med. 2007;8(suppl 2):S7-S13]
Renin–Angiotensin System Modulation for Treatment and Prevention of Cardiovascular Diseases: Toward an Optimal Therapeutic Strategy Renin Inhibition in Hypertension
The unraveling of the role of the renin–angiotensin system (RAS) in health and disease is an example of how basic and applied scientists can decipher a complex biological system to better understand the pathophysiology of disease. Moreover, clinicians have been provided with drugs to modulate the RAS, including the angiotensin-converting enzyme (ACE) inhibitors and angiotensin receptor blockers (ARBs). ACE inhibitors and ARBs have revolutionized the way in which many diseases are treated, including hypertension, heart failure, diabetes mellitus, and kidney disease. Yet, despite the undoubted successes of these drugs, cardiovascular morbidity and mortality remain high. Clearly, lower blood pressure goals may be required. Because ACE inhibitors and ARBs target specific areas of the RAS, more impressive results might be obtained with a more global reduction in RAS activity. This article examines the results of clinical trials of ACE inhibitors and ARBs and assesses the potential for improving outcomes through a more global inhibition of the RAS with renin inhibitors. [Rev Cardiovasc Med. 2007;8(suppl 2):S14-S21]
The Efficacy of Aliskiren, a Direct Renin Inhibitor, in the Treatment of Hypertension Renin Inhibition in Hypertension
Aliskiren is a potent, highly specific renin inhibitor with better oral bioavailability than earlier renin inhibitors and a long plasma half-life that makes it suitable for once-daily dosing. The efficacy and safety of aliskiren in treating hypertension has been studied in clinical trials both as monotherapy, comparing it with existing antihypertensive therapies, and in combination with other antihypertensive agents, including the diuretic hydrochlorothiazide, the angiotensin-converting enzyme inhibitor ramipril, and the calcium channel blocker amlodipine. From the extensive database acquired to date, it is clear that aliskiren is an effective antihypertensive agent, with once-daily administration resulting in dose-dependent systolic and diastolic blood pressure reductions. Combinations with existing antihypertensives are producing promising additional blood pressure–lowering effects. [Rev Cardiovasc Med. 2007;8(suppl 2):S22-S30]