Document Detail


Recent changes in the landscape of combination RAS blockade.
MedLine Citation:
PMID:  19900020     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
The renin-angiotensin system (RAS) is a prime target for cardiovascular drug therapy. Inhibition of the RAS lowers blood pressure and confers protection against cardiovascular and renal events. These latter benefits cannot be entirely attributed to blood pressure lowering. Angiotensin-converting enzyme (ACE)-inhibitors and angiotensin receptor blockers (ARBs) have been studied extensively and, while there is irrefutable evidence that these agents mitigate the risk for cardiovascular and renal events, their protection is incomplete. In outcomes studies that have employed ACE-inhibitors or ARBs there has been a relatively high residual event rate in the treatment arm and this has been ascribed, by some, to the fact that neither ACE-inhibitors nor ARBs completely repress RAS. For this reason, combined RAS blockade with an ACE-inhibitor and ARB has emerged as a therapeutic option. In hypertension, combined RAS blockade elicits only a marginal incremental drop in blood pressure and it does not further lower the risk for cardiovascular events. In chronic heart failure and proteinuric renal disease, combining these agents in carefully selected patients is associated with a reduction in clinical events. Irrespective of the setting, dual RAS blockade is associated with an increase in the risk for adverse events, primarily hyperkalemia and worsening renal function. The emergence of the direct renin inhibitor, aliskiren, has afforded clinicians a new strategy for RAS blockade. Renin system blockade with aliskiren plus another RAS agent is the subject of ongoing large-scale clinical trials and early studies suggest promise for this strategy. Currently, combined RAS blockade with an ACE-inhibitor and an ARB should not be routinely employed for hypertension; however, the combination of an ACE-inhibitor or ARB with aliskiren might be considered in some patients given the more formidable blood pressure-lowering profile of this regimen. In carefully selected patients with heart failure or kidney disease, combination therapy with two RAS inhibitors should be considered.
Authors:
Benjamin J Epstein; Steven M Smith; Rushab Choksi
Publication Detail:
Type:  Journal Article; Review    
Journal Detail:
Title:  Expert review of cardiovascular therapy     Volume:  7     ISSN:  1744-8344     ISO Abbreviation:  Expert Rev Cardiovasc Ther     Publication Date:  2009 Nov 
Date Detail:
Created Date:  2009-11-10     Completed Date:  2010-02-23     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  101182328     Medline TA:  Expert Rev Cardiovasc Ther     Country:  England    
Other Details:
Languages:  eng     Pagination:  1373-84     Citation Subset:  IM    
Affiliation:
Department of Pharmacotherapy, University of Florida, FL, USA.
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MeSH Terms
Descriptor/Qualifier:
Amides / therapeutic use
Angiotensin II Type 1 Receptor Blockers / adverse effects,  pharmacology,  therapeutic use*
Angiotensin-Converting Enzyme Inhibitors / adverse effects,  pharmacology,  therapeutic use*
Antihypertensive Agents / adverse effects,  pharmacology,  therapeutic use
Blood Pressure / drug effects
Cardiovascular Diseases / physiopathology,  prevention & control*
Drug Therapy, Combination
Fumarates / therapeutic use
Heart Failure / drug therapy,  physiopathology
Humans
Hypertension / drug therapy,  physiopathology
Kidney Diseases / drug therapy,  physiopathology
Renin / antagonists & inhibitors
Renin-Angiotensin System / drug effects*,  physiology
Chemical
Reg. No./Substance:
0/Amides; 0/Angiotensin II Type 1 Receptor Blockers; 0/Angiotensin-Converting Enzyme Inhibitors; 0/Antihypertensive Agents; 0/Fumarates; 0/aliskiren; EC 3.4.23.15/Renin

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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