Aliskiren/valsartan combination for the treatment of cardiovascular and renal diseases

Yarows, Steven A.

doi:10.1586/erc.09.143

Cited by 15 publications

(12 citation statements)

References 87 publications

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“…Combination therapy with aliskiren/losartan or aliskiren monotherapy significantly reduced plasma aldosterone from baseline by 21% and 25%, respectively, after 9 months of treatment compared with a 5% increase with losartan monotherapy in the ALLAY study [90]. In the AVOID study; aliskiren administered with losartan reduced urinary aldosterone from baseline by 24%, compared to 4% reduction with placebo [92].…”

Section: Direct Renin Inhibitor/arb or Ace Inhibitor Combinationmentioning

confidence: 94%

Rationale for Combining a Direct Renin Inhibitor with other Renin- Angiotensin System Blockers. Focus on Aliskiren and Combinations

Siragy

2011

Cardiovasc Drugs Ther

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Inhibition of the renin-angiotensin system has been a highly successful therapeutic approach for the prevention of hypertension-related end organ damage. Angiotensin converting enzyme inhibitors and angiotensin II receptor blockers lower blood pressure and reduce morbidity and mortality in patients with cardiovascular and kidney disease. However, progression to end-stage disease remains common in these patient populations. A compensatory increase in plasma renin activity occurs with the use of either angiotensin converting enzyme inhibitors or angiotensin II receptor blockers, thus causing increased levels of angiotensin II, which may limit the therapeutic effectiveness of these agents. The direct renin inhibitor, aliskiren, suppresses the renin-angiotensin system by inhibiting its first and rate-limiting step. This early inhibition reduces the production of all downstream components of the system. In this review, recent clinically relevant advances in the understanding of renin-angiotensin system biology are explored as a rationale for combining aliskiren with other blockers of the renin-angiotensin system. These combinations more fully inhibit the renin-angiotensin system, with the goal of providing additional therapeutic benefits in diseases associated with chronic activation of the renin-angiotensin system.

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Section: Direct Renin Inhibitor/arb or Ace Inhibitor Combinationmentioning

confidence: 94%

Rationale for Combining a Direct Renin Inhibitor with other Renin- Angiotensin System Blockers. Focus on Aliskiren and Combinations

Siragy

2011

Cardiovasc Drugs Ther

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“…By inhibiting the enzymatic conversion by renin of Agt to Ang I, DRIs inhibit the initial and rate-limiting step in the RAAS cascade, thus reducing the production of all downstream products derived from Agt [50,51]. Furthermore, in both clinical studies [52] and in experimental animals [14], aliskiren reduces plasma and/or urinary excretion of aldosterone. The role of aldosterone in endothelial dysfunction, inflammation, proteinuria and fibrosis is well known [30].…”

Section: Blockade Of the Raas In Ckdmentioning

confidence: 99%

Role of the Intrarenal Renin-Angiotensin-Aldosterone System in Chronic Kidney Disease

Siragy

Carey²

2010

Am J Nephrol

233

173

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The existence of local or tissue-based renin-angiotensin-aldosterone systems (RAAS) is well documented and has been implicated as a key player in the pathogenesis of cardiovascular and renal diseases. The kidney contains all elements of the RAAS, and intrarenal formation of angiotensin II not only controls glomerular hemodynamics and tubule sodium transport, but also activates a number of inflammatory and fibrotic pathways. Experimental and clinical studies have shown that the intrarenal RAAS is activated early in diabetic nephropathy, the leading cause of chronic kidney disease (CKD). Although angiotensin-converting enzyme inhibitors and angiotensin receptor blockers decrease the rate of decline in kidney function in patients with diabetic and non-diabetic nephropathy, many patients still progress to end-stage renal disease or die from cardiovascular events. There is still a clear need for additional strategies to block the RAAS more effectively to reduce progression of CKD. The focus of this paper is to review the importance of the intrarenal RAAS in CKD and recent findings in renin-angiotensin biology pertinent to the kidney. We also discuss additional strategies to inhibit the RAAS more effectively and the potential impact of direct renin inhibition on the prevention and management of CKD.

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“…In addition, a clinical study reported that aliskiren reduces plasma and urinary excretion of aldosterone and thus may provide additional renoprotective effects (74). This drug has been shown to be an effective antihypertensive agent and some studies have also evaluated aliskiren as a potential renoprotective agent in CKD using proteinuria as a surrogate marker of CKD progression (8, 75 -78).…”

Section: Ras Drugsmentioning

confidence: 99%

Renin^|^ndash;Angiotensin System, Hypertension, and Chronic Kidney Disease: Pharmacogenetic Implications

2012

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Abstract. About 80% of CKD (chronic kidney disease) patients are hypertensive, and kidney function and blood pressure are clearly related to both physiologic and pathologic conditions in a "vicious cycle". In this pathologic scenario, there is a renin-angiotensin system (RAS) hyperactivity associated to progression of renal damage. Current guidelines indicate as the first choice of antihypertensive intervention, the pharmacologic blockade of the RAS. Nonetheless, both response to treatment and renal protection have considerable inter-individual variability. The main aims of this review are to describe the genetic characteristics of RAS components and to identify the possible pharmacogenetic implications for RAS-blocker drugs in the hypertension-CKD scenario. To date, RAS polymorphisms have not been consistently associated to antihypertensive response and studies focusing on CKD are scarce. Nonetheless, pharmacogenetic studies for the RAS-blocker drugs could still be further explored, especially with new generation tools and focusing not only on the antihypertensive response, but also on renal protection as well.

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Aliskiren/valsartan combination for the treatment of cardiovascular and renal diseases

Cited by 15 publications

References 87 publications

Rationale for Combining a Direct Renin Inhibitor with other Renin- Angiotensin System Blockers. Focus on Aliskiren and Combinations

Rationale for Combining a Direct Renin Inhibitor with other Renin- Angiotensin System Blockers. Focus on Aliskiren and Combinations

Role of the Intrarenal Renin-Angiotensin-Aldosterone System in Chronic Kidney Disease

Renin^|^ndash;Angiotensin System, Hypertension, and Chronic Kidney Disease: Pharmacogenetic Implications

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