Document Detail


Current Strategies to Achieve Further Cardiac and Renal Protection through Enhanced Renin-Angiotensin-Aldosterone System Inhibition.
MedLine Citation:
PMID:  21241234     Owner:  NLM     Status:  Publisher    
Abstract/OtherAbstract:
An incomplete inhibition of the renin angiotensin aldosterone system (RAAS) may be responsible for the residual organ damage and event rate that still occur in spite of an apparent blood pressure control in patients with hypertension, diabetes, chronic kidney disease and heart failure treated with angiotensin converting enzyme inhibitors (ACEI) or angiotensin receptor blockers (ARB). Additional antiproteinuric effect in diabetic and non diabetic chronic kidney disease, and reduction in hospitalizations in patients with heart failure already receiving a single RAAS antagonist, has been achieved by incremental inhibition of the RAAS with dual therapy or uptitration of an individual agent above conventional dosages. However, the synergistic increase in plasma renin activity (PRA) and the angiotensin II escape could reduce the expected benefit obtained with dual therapy. Results from ONTARGET showing a lack of additional outcome benefit over monotherapy, with a concomitant increase risk of hyperkalemia, renal impairment, and hypotension, discourage the use of the ACEI/ARB combination in patients at high risk of cardiovascular events. This occured despite a lower albumin excretion in dual versus single RAAS blockade, indicating that an incremental antiproteinuric effect is not automatically translated into clinical outcome benefits. The efficacy and safety of ACEI/ARB combination versus monotherapy in patients with overt proteinuria is currently evaluated by LIRICO and VA NEPHRON-D clinical trials. The long lasting direct renin inhibitor aliskiren, acting at the first and rate limiting step of the RAAS cascade, prevents the reactive increase in PRA when combined with ACEIs, ARBs or diuretics. The ASPIRE HIGHER programme, involving more than 35,000 patients with hypertension, heart failure, kidney disease and diabetes, is currently evaluating the efficacy and safety of aliskiren on top of standard therapy. The clinical benefit of adding mineralocorticoid receptor blockers (MRBs) in the control of resistant hypertension, proteinuric kidney diseases, and prevention of mortality in patients with heart failure on top of conventional treatment, evidences the pathogenic role of inadequately suppressed aldosterone as a cause of suboptimal response to conventional RAAS inhibition. The present review will focus on the pathophysiological ground, and the evidence provided by clinical trials assessing the efficacy and safety of recent strategies for the prevention of cardiovascular events and target organ damage progression via enhanced RAAS inhibition.
Authors:
J Alfie; L S Aparicio; G D Waisman
Related Documents :
10406014 - Subarachnoid blood infusion versus raised intracranial pressure: effects on the amino a...
18564824 - The early response of mannitol infusion in traumatic brain injury.
7070614 - Furosemide in the intraoperative reduction of intracranial pressure in the patient with...
17272764 - Continuous monitoring of cerebrovascular autoregulation after subarachnoid hemorrhage b...
24801134 - Hypercortisolism in obesity-associated hypertension.
21242364 - Culturally appropriate storytelling to improve blood pressure: a randomized trial.
Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2011-1-14
Journal Detail:
Title:  Reviews on recent clinical trials     Volume:  -     ISSN:  1876-1038     ISO Abbreviation:  -     Publication Date:  2011 Jan 
Date Detail:
Created Date:  2011-1-18     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  101270873     Medline TA:  Rev Recent Clin Trials     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Affiliation:
Unidad de Hipertension Arterial, Servicio de Clinica Medica, Hospital Italiano de Buenos Aires, Gascon 450 (1181), Buenos Aires, Argentina. jose.alfie@hospitalitaliano.org.ar.
Export Citation:
APA/MLA Format     Download EndNote     Download BibTex
MeSH Terms
Descriptor/Qualifier:

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


Previous Document:  Design And Endpoints Of Clinical And Translational Trials In Advanced Colorectal Cancer. A Proposal ...
Next Document:  Is there Evidence to Support the Use of Direct Factor Xa Inhibitors in Coronary Artery Disease?