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Recent changes in the landscape of combination RAS blockade.
Expert Rev Cardiovasc Ther. 2009 Nov; 7(11):1373-84.ER

Abstract

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+Show Affiliations

Department of Pharmacotherapy, University of Florida, FL, USA.No affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Review

Language

eng

PubMed ID

19900020

Citation

Epstein, Benjamin J., et al. "Recent Changes in the Landscape of Combination RAS Blockade." Expert Review of Cardiovascular Therapy, vol. 7, no. 11, 2009, pp. 1373-84.
Epstein BJ, Smith SM, Choksi R. Recent changes in the landscape of combination RAS blockade. Expert Rev Cardiovasc Ther. 2009;7(11):1373-84.
Epstein, B. J., Smith, S. M., & Choksi, R. (2009). Recent changes in the landscape of combination RAS blockade. Expert Review of Cardiovascular Therapy, 7(11), 1373-84. https://doi.org/10.1586/erc.09.127
Epstein BJ, Smith SM, Choksi R. Recent Changes in the Landscape of Combination RAS Blockade. Expert Rev Cardiovasc Ther. 2009;7(11):1373-84. PubMed PMID: 19900020.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Recent changes in the landscape of combination RAS blockade. AU - Epstein,Benjamin J, AU - Smith,Steven M, AU - Choksi,Rushab, PY - 2009/11/11/entrez PY - 2009/11/11/pubmed PY - 2010/2/24/medline SP - 1373 EP - 84 JF - Expert review of cardiovascular therapy JO - Expert Rev Cardiovasc Ther VL - 7 IS - 11 N2 - 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. SN - 1744-8344 UR - https://www.unboundmedicine.com/medline/citation/19900020/Recent_changes_in_the_landscape_of_combination_RAS_blockade_ L2 - https://www.tandfonline.com/doi/full/10.1586/erc.09.127 DB - PRIME DP - Unbound Medicine ER -