Document Detail


Effects of candesartan in patients with chronic heart failure and reduced left-ventricular systolic function taking angiotensin-converting-enzyme inhibitors: the CHARM-Added trial.
MedLine Citation:
PMID:  13678869     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
BACKGROUND: Angiotensin II type 1 receptor blockers have favourable effects on haemodynamic measurements, neurohumoral activity, and left-ventricular remodelling when added to angiotensin-converting-enzyme (ACE) inhibitors in patients with chronic heart failure (CHF). We aimed to find out whether these drugs improve clinical outcome.
METHODS: Between March, 1999, and November, 1999, we enrolled 2548 patients with New York Heart Association functional class II-IV CHF and left-ventricular ejection fraction 40% or lower, and who were being treated with ACE inhibitors. We randomly assigned patients candesartan (n=1276, target dose 32 mg once daily) or placebo (n=1272). At baseline, 55% of patients were also treated with beta blockers and 17% with spironolactone. The primary outcome of the study was the composite of cardiovascular death or hospital admission for CHF. Analysis was done by intention to treat.
FINDINGS: The median follow-up was 41 months. 483 (38%) patients in the candesartan group and 538 (42%) in the placebo group experienced the primary outcome (unadjusted hazard ratio 0.85 [95% CI 0.75-0.96], p=0.011; covariate adjusted p=0.010). Candesartan reduced each of the components of the primary outcome significantly, as well as the total number of hospital admissions for CHF. The benefits of candesartan were similar in all predefined subgroups, including patients receiving baseline beta blocker treatment.
INTERPRETATION: The addition of candesartan to ACE inhibitor and other treatment leads to a further clinically important reduction in relevant cardiovascular events in patients with CHF and reduced left-ventricular ejection fraction.
Authors:
John J V McMurray; Jan Ostergren; Karl Swedberg; Christopher B Granger; Peter Held; Eric L Michelson; Bertil Olofsson; Salim Yusuf; Marc A Pfeffer;
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Publication Detail:
Type:  Clinical Trial; Comparative Study; Journal Article; Multicenter Study; Randomized Controlled Trial; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Lancet     Volume:  362     ISSN:  1474-547X     ISO Abbreviation:  Lancet     Publication Date:  2003 Sep 
Date Detail:
Created Date:  2003-09-18     Completed Date:  2003-10-27     Revised Date:  2013-05-28    
Medline Journal Info:
Nlm Unique ID:  2985213R     Medline TA:  Lancet     Country:  England    
Other Details:
Languages:  eng     Pagination:  767-71     Citation Subset:  AIM; IM    
Affiliation:
University of Glasgow, Glasgow, UK. j.mcmurray@bio.gla.ac.uk
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MeSH Terms
Descriptor/Qualifier:
Adolescent
Adult
Angiotensin Receptor Antagonists
Angiotensin-Converting Enzyme Inhibitors / therapeutic use*
Antihypertensive Agents / therapeutic use*
Benzimidazoles / therapeutic use*
Cardiac Output, Low / drug therapy,  epidemiology,  mortality
Cardiovascular Diseases / mortality
Comorbidity
Drug Administration Schedule
Drug Therapy, Combination
Female
Follow-Up Studies
Heart Failure / drug therapy*,  epidemiology,  mortality
Hospitalization
Humans
Male
Placebos
Tetrazoles / therapeutic use*
Treatment Outcome
Ventricular Dysfunction, Left / drug therapy*,  epidemiology,  mortality
Chemical
Reg. No./Substance:
0/Angiotensin Receptor Antagonists; 0/Angiotensin-Converting Enzyme Inhibitors; 0/Antihypertensive Agents; 0/Benzimidazoles; 0/Placebos; 0/Tetrazoles; S8Q36MD2XX/candesartan
Comments/Corrections
Comment In:
ACP J Club. 2004 Mar-Apr;140(2):32-3   [PMID:  15122853 ]
Lancet. 2003 Nov 15;362(9396):1675-6; author reply 1678-9   [PMID:  14630453 ]
Lancet. 2003 Sep 6;362(9386):754-5   [PMID:  13678864 ]
J Fam Pract. 2004 Feb;53(2):93-4   [PMID:  14764285 ]
Lancet. 2003 Nov 15;362(9396):1677; author reply 1678-9   [PMID:  14630456 ]

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


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