Document Detail


Adverse mortality effect of central sympathetic inhibition with sustained-release moxonidine in patients with heart failure (MOXCON).
MedLine Citation:
PMID:  14607206     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
BACKGROUND: The association between sympathetic activation and mortality in chronic heart failure and the favorable effect of beta blocking drugs has raised the possibility of therapeutic efficacy for central sympathetic inhibition with sustained-release (SR) moxonidine, an imidazoline receptor agonist.
METHODS: A randomized double-blind, placebo-controlled trial was initiated in 425 centers in 17 countries with a plan to enter 4533 patients with New York Heart Association class II-IV heart failure and a reduced ejection fraction. Moxonidine SR or matching placebo was titrated to a target dose of 1.5 mg BID. The trial was powered to detect a 20% reduction in mortality, which required a total of 724 deaths.
FINDINGS: An early increase in death rate and adverse events in the moxonidine SR group led to premature termination of the trial because of safety concerns after 1934 patients were entered. Final analysis revealed 54 deaths (5.5%) in the moxonidine SR group and 32 deaths (3.4%) in the placebo group during the active treatment phase. Survival curves revealed a significantly (P=0.012) worse outcome in the moxonidine SR group. Hospitalization for heart failure, acute myocardial infarction and adverse events were also more frequent in the moxonidine SR group. Plasma norepinephrine was significantly decreased by moxonidine SR (-18.8% from baseline) vs. placebo (+6.9%).
INTERPRETATION: Early termination of the trial limited conclusions regarding the long-term effects of central sympathetic inhibition. Nonetheless, the excess early mortality and morbidity suggest the likelihood of an adverse effect of moxonidine SR and raise concerns regarding the efficacy of generalized sympathetic inhibition in heart failure.
Authors:
Jay N Cohn; Marc A Pfeffer; Jean Rouleau; Norman Sharpe; Karl Swedberg; Matthias Straub; Curtis Wiltse; Theressa J Wright;
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Publication Detail:
Type:  Clinical Trial; Journal Article; Multicenter Study; Randomized Controlled Trial; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  European journal of heart failure     Volume:  5     ISSN:  1388-9842     ISO Abbreviation:  Eur. J. Heart Fail.     Publication Date:  2003 Oct 
Date Detail:
Created Date:  2003-11-10     Completed Date:  2004-03-12     Revised Date:  2011-06-08    
Medline Journal Info:
Nlm Unique ID:  100887595     Medline TA:  Eur J Heart Fail     Country:  Netherlands    
Other Details:
Languages:  eng     Pagination:  659-67     Citation Subset:  IM    
Affiliation:
Cardiovascular Division, Mayo Mail Code 508, University of Minnesota Medical School, 420 Delaware Street SE, Minneapolis, MN 55455, USA. cohnx001@umn.edu
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MeSH Terms
Descriptor/Qualifier:
Delayed-Action Preparations
Double-Blind Method
Female
Heart Failure / drug therapy*,  mortality*
Humans
Imidazoles / administration & dosage,  adverse effects*,  therapeutic use*
Male
Middle Aged
Norepinephrine / blood
Safety
Survival Rate
Sympathetic Nervous System / drug effects
Sympatholytics / administration & dosage,  adverse effects*,  therapeutic use*
Chemical
Reg. No./Substance:
0/Delayed-Action Preparations; 0/Imidazoles; 0/Sympatholytics; 51-41-2/Norepinephrine; 75438-57-2/moxonidine

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


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