Document Detail


Direct renin inhibition in addition to or as an alternative to angiotensin converting enzyme inhibition in patients with chronic systolic heart failure: rationale and design of the Aliskiren Trial to Minimize OutcomeS in Patients with HEart failuRE (ATMOSPHERE) study.
MedLine Citation:
PMID:  21169387     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
The renin-angiotensin-aldosterone system (RAAS) represents a key therapeutic target in heart failure (HF) management. However, conventional agents that block this system induce a reflex increase in plasma renin activity (PRA), which may lead to RAAS 'escape'. Direct renin inhibitors (DRIs) have been developed that decrease PRA and thus may provide a greater RAAS blockade. Aliskiren is the first orally active DRI. Plasma levels of B-type natriuretic peptide (BNP) have been observed to be reduced with aliskiren compared with placebo. The aim of the Aliskiren Trial of Minimizing OutcomeS for Patients with HEart failuRE (ATMOSPHERE) study is to evaluate the effect of both aliskiren and enalapril monotherapy and aliskiren/enalapril combination therapy on cardiovascular death and HF hospitalization in patients with chronic systolic HF, NYHA functional class II-IV symptoms, and elevated plasma levels of BNP. Methods Patients tolerant to at least 10 mg or equivalent of enalapril will undergo an open-label run-in period where they receive enalapril then aliskiren. Approximately 7000 patients tolerating this run-in period will then be randomized 1:1:1 to aliskiren monotherapy, enalapril monotherapy, or the combination. The primary endpoints of ATMOSPHERE are (i) whether the aliskiren/enalapril combination is superior to enalapril monotherapy in delaying time to first occurrence of cardiovascular death or HF hospitalization and (ii) whether aliskiren monotherapy is superior or at least non-inferior to enalapril monotherapy on this endpoint. Perspective The ATMOSPHERE study will definitively determine the role of a DRI strategy additional to or as an alternative to conventional RAAS blockade in patients with chronic systolic HF.
Authors:
Henry Krum; Barry Massie; William T Abraham; Kenneth Dickstein; Lars Kober; John J V McMurray; Ashkay Desai; Claudio Gimpelewicz; Albert Kandra; Bernard Reimund; Henning Rattunde; Juergen Armbrecht;
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  European journal of heart failure     Volume:  13     ISSN:  1879-0844     ISO Abbreviation:  Eur. J. Heart Fail.     Publication Date:  2011 Jan 
Date Detail:
Created Date:  2010-12-20     Completed Date:  2011-04-05     Revised Date:  2013-05-20    
Medline Journal Info:
Nlm Unique ID:  100887595     Medline TA:  Eur J Heart Fail     Country:  Netherlands    
Other Details:
Languages:  eng     Pagination:  107-14     Citation Subset:  IM    
Affiliation:
Centre of Cardiovascular Research & Education in Therapeutics, Department of Epidemiology & Preventive Medicine, Monash University/Alfred Hospital, Melbourne VIC 3004, Australia. henry.krum@med.monash.edu.au
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MeSH Terms
Descriptor/Qualifier:
Amides / therapeutic use*
Angiotensin-Converting Enzyme Inhibitors / therapeutic use*
Antihypertensive Agents / therapeutic use*
Disease Progression
Double-Blind Method
Drug Therapy, Combination
Enalapril / therapeutic use
Fumarates / therapeutic use*
Heart Failure, Systolic / drug therapy*
Humans
Natriuretic Peptide, Brain / blood
Randomized Controlled Trials as Topic
Renin / antagonists & inhibitors*,  drug effects
Renin-Angiotensin System / drug effects*
Research Design
Stroke Volume
Ventricular Function, Left
Chemical
Reg. No./Substance:
0/Amides; 0/Angiotensin-Converting Enzyme Inhibitors; 0/Antihypertensive Agents; 0/Fumarates; 114471-18-0/Natriuretic Peptide, Brain; 502FWN4Q32/aliskiren; 75847-73-3/Enalapril; EC 3.4.23.15/Renin
Investigator
Investigator/Affiliation:
H Krum / ; B Massie / ; W Abraham / ; K Dickstein / ; L Kober / ; J McMurray / ; Karl Swedberg / ; Stuart Pocock / ; Bertram Pitt / ; S Borer Jeffrey / ; Jean Rouleau / ; Martina Wibberg / ; Scott Solomon / ; S Desai Akshay / ; Peter Finn / ; Larry Weinrauch / ; Howard Hartley / ; Anne-Catherine Pouleur / ; Ebrahim Barkoudah / ; Chau Duong / ; Austin Rogers /

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


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