Document Detail

Is there a future for direct renin inhibitors?
MedLine Citation:
PMID:  20380486     Owner:  NLM     Status:  MEDLINE    
IMPORTANCE OF THE FIELD: The renin-angiotensin-aldosterone system (RAAS) is a key regulator of blood pressure (BP), as well as volume and electrolytes, in both hypertensive and normotensive individuals. Inappropriate activation of the RAAS is important in hypertension-induced cardiovascular disease (CVD) and chronic kidney disease (CKD). Renin is the rate-limiting step in the RAAS cascade, which makes direct renin inhibitors (DRIs) an attractive target for RAAS suppression and treatment of hypertension. Current regimens using either angiotensin-converting enzyme inhibitor (ACEi) or angiotensin receptor blocker (ARB) result in feedback upregulation of renin and aldosterone breakthrough, which contribute to incomplete suppression of the RAAS. Thereby, aliskiren - alone or in combination - might offer a novel therapeutic intervention to improve suppression of the RAAS, with potential to translate to improved CVD and CKD outcomes. AREAS COVERED IN THIS REVIEW: Herein, we present the current state of knowledge of DRIs in the preclinical and clinical realm and their antihypertensive efficacy in relation to cardiovascular and renal risk. Recent clinical trials (2007 - 2009) support the efficacy of aliskiren, and studies suggest the potential for improved CVD and CKD outcomes. WHAT THE READER WILL GAIN: An understanding of the mechanism of action of DRIs and a perspective of recent clinical trials. TAKE HOME MESSAGE: The DRI aliskiren is an effective antihypertensive agent that preliminary data suggests has a beneficial effect in CVD and CKD. Combination of aliskiren with an ACEi or ARB may be better tolerated than the ACEi-ARB combination. Future work is needed to further quantify aliskiren's impact on hard CVD and CKD end points.
Kunal Chaudhary; Ravi Nistala; Adam Whaley-Connell
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Publication Detail:
Type:  Journal Article; Review    
Journal Detail:
Title:  Expert opinion on investigational drugs     Volume:  19     ISSN:  1744-7658     ISO Abbreviation:  Expert Opin Investig Drugs     Publication Date:  2010 May 
Date Detail:
Created Date:  2010-04-20     Completed Date:  2010-07-08     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  9434197     Medline TA:  Expert Opin Investig Drugs     Country:  England    
Other Details:
Languages:  eng     Pagination:  653-61     Citation Subset:  IM    
Harry S Truman VA Medical Center, Columbia, MO 65211, USA.
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MeSH Terms
Amides / adverse effects,  pharmacology
Antihypertensive Agents / adverse effects,  pharmacology*
Blood Pressure / drug effects
Cardiovascular Diseases / etiology,  prevention & control
Drug Design
Drug Therapy, Combination
Fumarates / adverse effects,  pharmacology
Hypertension / complications,  drug therapy*,  physiopathology
Kidney Diseases / etiology,  prevention & control
Renin / antagonists & inhibitors*
Renin-Angiotensin System / drug effects
Reg. No./Substance:
0/Amides; 0/Antihypertensive Agents; 0/Fumarates; 0/aliskiren; EC

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