| Synergistic efficacy of enalapril and losartan on exercise performance and oxygen consumption at peak exercise in congestive heart failure. | |
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MedLine Citation:
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PMID: 10569660 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Oxygen consumption at peak exercise (peak VO2) is a strong independent predictor of the outcome in congestive heart failure (CHF). Renin-angiotensin system inhibition with either ACE or AT1 receptor blockers is effective on peak VO2. We evaluated whether mechanisms are similar for the 2 categories of drugs and whether their combination is able to produce a synergistic effect. Twenty CHF patients were randomized to receive, in a double-blind fashion, placebo + placebo (P+P), enalapril (20 mg/day) + placebo (E+P), losartan (50 mg/day) + placebo (L+P), and enalapril + losartan (E+L) or the same preparations in a reverse order, each for 8 weeks. Two patients did not complete the trial. Pulmonary function, cardiopulmonary exercise test, plasma neurohormones, and quality of life were assessed at the end of each treatment. Compared with P+P, E+P, and L+P similarly (16% and 15%, respectively) and significantly (p <0.01) augmented peak VO2. Enalapril improved lung function (reduced slope of ventilation vs carbon dioxide production and dead space to tidal volume ratio, and increased alveolar membrane conductance and tidal volume). Losartan likely activated the exercising muscle perfusion (raised delta VO2/delta work rate, which is a measure of aerobic work efficiency). In combination, they further increased peak VO2, 10% from E+P (p <0.05) and 11% from L+P (p <0.05). Compared with run-in, E+P and L+P significantly reduced plasma norepinephrine by 70 +/- 14 pg/ml and 100 +/- 16 pg/ml and aldosterone by 1.6 +/- 0.7 ng/dl and 1.6 +/- 0.8 ng/dl. These changes were significantly greater when the drugs were combined (140 +/- 20 pg/ml for norepinephrine, and 5.6 +/- 0.9 ng/dl for aldosterone). Quality-of-life score did not improve significantly at each treatment step. Thus, lorsartan and enalapril similarly increased peak VO2 in CHF patients, but mediators of this effect were, at least in part, different therapeutic targets that may be synergistic when the 2 drugs are combined. |
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Authors:
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M Guazzi; P Palermo; G Pontone; F Susini; P Agostoni |
Publication Detail:
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Type: Clinical Trial; Journal Article; Randomized Controlled Trial; Research Support, Non-U.S. Gov't |
Journal Detail:
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Title: The American journal of cardiology Volume: 84 ISSN: 0002-9149 ISO Abbreviation: Am. J. Cardiol. Publication Date: 1999 Nov |
Date Detail:
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Created Date: 1999-11-30 Completed Date: 1999-11-30 Revised Date: 2007-11-15 |
Medline Journal Info:
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Nlm Unique ID: 0207277 Medline TA: Am J Cardiol Country: UNITED STATES |
Other Details:
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Languages: eng Pagination: 1038-43 Citation Subset: AIM; IM |
Affiliation:
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Istituto di Cardiologia dell'Università degli Studi, Centro di Studio per le Ricerche Cardiovascolari del Consiglio Nazionale delle Ricerche, Fondazione Monzino, I.R.C.C.S, Milan, Italy. cardguaz@imiucca.csi.unimi.it |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Adult Aged Angiotensin-Converting Enzyme Inhibitors / administration & dosage*, adverse effects Cross-Over Studies Double-Blind Method Drug Synergism Enalapril / administration & dosage*, adverse effects Exercise Test / drug effects* Female Heart Failure / drug therapy* Humans Losartan / administration & dosage*, adverse effects Male Middle Aged Oxygen Consumption / drug effects* Receptors, Angiotensin / antagonists & inhibitors* Treatment Outcome |
| Chemical | |
Reg. No./Substance:
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0/Angiotensin-Converting Enzyme Inhibitors; 0/Receptors, Angiotensin; 114798-26-4/Losartan; 75847-73-3/Enalapril |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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