Document Detail


Addition of candesartan to angiotensin converting enzyme inhibitor therapy in patients with chronic heart failure does not reduce levels of oxidative stress.
MedLine Citation:
PMID:  11959049     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
BACKGROUND: Angiotensin II exerts a number of harmful effects in patients with chronic heart failure (CHF) and, through an increase in oxidative stress, is thought to be critical in the development of endothelial dysfunction. Angiotensin II may be elevated in CHF despite treatment with angiotensin converting enzyme (ACE) inhibitors, producing a rationale for adjunctive angiotensin receptor blockade. We investigated whether the addition of angiotensin antagonism to ACE inhibition would reduce oxidative stress and improve endothelial function and exercise tolerance in patients with chronic heart failure.
METHODS AND RESULTS: Twenty-eight heart failure patients, who were on stable ACE inhibitor therapy, were randomised to receive adjunctive therapy with candesartan or placebo. Plasma lipid-derived free radicals, TBARS and neutrophil O2-generation, markers of oxidative stress, were measured in venous blood. Arterial endothelial function was assessed as the response of the brachial artery to flow-related shear stress. Exercise capacity was determined by cardiopulmonary exercise testing. Compared with placebo, candesartan had no effect on changes in lipid derived free radicals (-0.1+/-1.2 vs. -0.1+/-1.0 units, respectively, P=NS), TBARS (-2.2+/-1.1 vs. -2.6+/-2.2 micromol/l, respectively, P=NS) or neutrophil O2-generating capacity (-7.3+/-5.1 vs. -8.4+/-7.9 mV/5x10(5) neutrophils, respectively, P=NS). There was no effect on changes in brachial artery flow-mediated dilatation (0.5+/-1.0 vs. 0.8+/-1.3%, respectively, P=NS) nor peak VO2 (1.6+/-0.7 ml/kg per min vs. 1.8+/-0.6 ml/kg per min; P=NS).
CONCLUSION: The addition of the candesartan to ACE inhibitor therapy had no effect on oxidative stress and did not improve endothelial function or exercise capacity in patients with CHF.
Authors:
Gethin R Ellis; Angus K Nightingale; Daniel J Blackman; Richard A Anderson; Catherine Mumford; Graham Timmins; Derek Lang; Simon K Jackson; Michael D Penney; Malcolm J Lewis; Michael P Frenneaux; Jayne Morris-Thurgood
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Publication Detail:
Type:  Clinical Trial; Comparative Study; Journal Article; Randomized Controlled Trial; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  European journal of heart failure     Volume:  4     ISSN:  1388-9842     ISO Abbreviation:  Eur. J. Heart Fail.     Publication Date:  2002 Mar 
Date Detail:
Created Date:  2002-04-17     Completed Date:  2002-05-22     Revised Date:  2013-05-28    
Medline Journal Info:
Nlm Unique ID:  100887595     Medline TA:  Eur J Heart Fail     Country:  Netherlands    
Other Details:
Languages:  eng     Pagination:  193-9     Citation Subset:  IM    
Affiliation:
Department of Cardiology, Royal Glamorgan Hospital, Llantrisant, Rhondda Cynon Taf, UK. gethin.ellis@pr-tr.nhs.wales.uk
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MeSH Terms
Descriptor/Qualifier:
Adult
Aged
Angiotensin-Converting Enzyme Inhibitors / therapeutic use*
Antihypertensive Agents / therapeutic use*
Benzimidazoles / therapeutic use*
Blood Pressure / drug effects
Brachial Artery / chemistry
Chronic Disease
Drug Therapy, Combination
Endothelium, Vascular / drug effects
Exercise Tolerance / drug effects
Female
Follow-Up Studies
Heart Failure / drug therapy*
Heart Rate / drug effects
Humans
Lipid Peroxidation / drug effects
Male
Middle Aged
Natriuretic Peptide, Brain / blood,  drug effects
Oxidative Stress / drug effects*
Stroke Volume / drug effects
Tetrazoles / therapeutic use*
Time Factors
Treatment Outcome
Chemical
Reg. No./Substance:
0/Angiotensin-Converting Enzyme Inhibitors; 0/Antihypertensive Agents; 0/Benzimidazoles; 0/Tetrazoles; 114471-18-0/Natriuretic Peptide, Brain; S8Q36MD2XX/candesartan

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


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